aterosklerozАтеросклерозAteroscleroz2078-256X2949-3633НИИТПМ-филиал ИЦиГ СО РАНateroskleroz-611Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESСтресс-зависимые механизмы развития метаболического синдрома: роль рецепторов, активируемых пролифераторами пероксисомStress-mediated mechanisms of metabolic syndrome development: the role of peroxisome proliferator activated receptorsХраповаМ. В.KhrapovaM. V.

Марина Валерьевна Храпова, канд. биол. наук, старший научный сотрудник

СО РАМН

ФГБУ «НИИ терапии»

лаборатория молекулярно-клеточных механизмов терапевтических заболеваний

630089

ул. Бориса Богаткова, 175/1

Новосибирск

SB RAMS

Establishment of the Russian Academy of Medical Sciences Research Institute of Therapy

630089

B. Bogatkova str., 175/1

Novosibirsk

ДушкинМ. И.DushkinM. I.

Михаил Иванович Душкин, д-р мед. наук, проф., зав. лабораторией

СО РАМН

ФГБУ «НИИ терапии»

лаборатория молекулярно-клеточных механизмов терапевтических заболеваний

630089

ул. Бориса Богаткова, 175/1

Новосибирск

SB RAMS

Establishment of the Russian Academy of Medical Sciences Research Institute of Therapy

630089

B. Bogatkova str., 175/1

Novosibirsk

midushkin@soramn.ruРАМНRAMS201130032022722343Copyright © Храпова М.В., Душкин М.И., 20222022Храпова М.В., Душкин М.И.Khrapova M.V., Dushkin M.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ateroskleroz.elpub.ru/jour/article/view/611

   Рассмотрены аспекты участия рецепторов, активируемых пролифераторами пероксисом (PPAR), в регуляции стресс-зависимых биологических процессов, приводящих к развитию резистентности к инсулину, нарушениям липидного обмена, гипертензии и развитию воспалительной реакции. На основе анализа литературы обосновывается утверждение о том, что PPAR играют центральную роль в трансдукции стрессовых сигналов, приводящих в условиях длительного действия стрессовых факторов к развитию метаболического дисбаланса. Особое внимание уделяется анализу взаимосвязи между изменениями функциональной активности трех изоформ PPAR и нарушениями регуляции метаболических процессов при стрессе. С учетом экспериментальных данных, описанных в литературе, предлагается концепция, которая рассматривает активацию PPAR при остром стрессе как адаптивную реакцию, тогда как при длительном стрессе или пролонгированном действии стрессовых медиаторов стойкая гиперэкспрессия PPAR может быть причиной развития резистентности к инсулину, гипертонии и висцерального ожирения. Обсуждается стратегия использования PPAR в качестве фармакологических мишеней метаболического синдрома.

   Some aspects of peroxisome proliferator activated receptors (PPAR) involvement in regulation of stress-dependent biological processes leading to insulin resistance, lipid imbalance, hypertension and inflammation are reviewed. Analysis of literature data clearly shows the main role of PPAR in stress signal transduction following to metabolic disbalance development under prolonged stress conditions. The interplay of three PPAR isoforms functional activity with metabolic process disturbances during stress is under special emphasis. Taking into account experimental data described in literature we suggest that PPAR activation under acute stress is an adaptive response while stable PPAR hyperexpression under proloned stress can cause insulin resistance, hypertension, and visceral obesity. The strategy of PPAR using as pharmacological targets in metabolic syndrome correction is under consideration.

рецепторыактивируемые пролифераторами пероксисомстрессметаболический синдром.PPARstressmetabolic syndromeReferencesCharmandari E., Tsigos C., Chrousos G. Endocrinology of the stress response // Annu. Rev. Physiol. 2005. Vol. 67. P. 259–284.Charmandari E., Tsigos C., Chrousos G. Endocrinology of the stress response // Annu. Rev. Physiol. 2005. Vol. 67. P. 259–284.Chandola T., Brunner E., Marmot M. Chronic stress at work and the metabolic syndrome: prospective study // BMJ. 2006. Vol. 332. P. 521–525.Chandola T., Brunner E., Marmot M. Chronic stress at work and the metabolic syndrome: prospective study // BMJ. 2006. Vol. 332. P. 521–525.Chichlowska K. L., Rose K. M., Diez-Roux A. V. et al. Individual and neighborhood socioeconomic status characteristics and prevalence of metabolic syndrome: the atherosclerosis risk in communities (ARIC) study // Psychosom. Med. 2008. V. 70. P. 986–992.Chichlowska K. L., Rose K. M., Diez-Roux A. V. et al. Individual and neighborhood socioeconomic status characteristics and prevalence of metabolic syndrome: the atherosclerosis risk in communities (ARIC) study // Psychosom. Med. 2008. V. 70. P. 986–992.Asensio C., Muzzin P., Rohner-Jeanrenaud F. Role of glucocorticoids in the physiopathology of excessive fat deposition and insulin resistance // Int. J. Obes. Relat. Metab. Disord. 2004. Vol. 28. (Suppl 4). P. S45–S52.Asensio C., Muzzin P., Rohner-Jeanrenaud F. Role of glucocorticoids in the physiopathology of excessive fat deposition and insulin resistance // Int. J. Obes. Relat. Metab. Disord. 2004. Vol. 28. (Suppl 4). P. S45–S52.Tsigos C., Chrousos G. P. Hypothalamic-pituitary-ad-renal axis, neuroendocrine factors and stress // J. Psychosom. Res. 2002. Vol. 53. P. 865–871.Tsigos C., Chrousos G. P. Hypothalamic-pituitary-ad-renal axis, neuroendocrine factors and stress // J. Psychosom. Res. 2002. Vol. 53. P. 865–871.Bjorntrop P., Rosmond R. Hypotolamic origin of the metabolic syndrome X // Ann. N. Y. Acad. Sci. 1999. Vol. 892. P. 297–307.Bjorntrop P., Rosmond R. Hypotolamic origin of the metabolic syndrome X // Ann. N. Y. Acad. Sci. 1999. Vol. 892. P. 297–307.Rosmond R., Bjorntrop P. The hypotolamic-pituitary-adrenalaxis activity as apredictor of cardiovascular disease, tipe 2 diabetes and stroke // J. Intern. Med. 2000. Vol. 247. P. 188–197.Rosmond R., Bjorntrop P. The hypotolamic-pituitary-adrenalaxis activity as apredictor of cardiovascular disease, tipe 2 diabetes and stroke // J. Intern. Med. 2000. Vol. 247. P. 188–197.Bragt M. C., Popeijus H. E. Peroxisome proliferator-activated receptors and the metabolic syndrome // Physiol. Behav. 2008. Vol. 94. P. 187–197.Bragt M. C., Popeijus H. E. Peroxisome proliferator-activated receptors and the metabolic syndrome // Physiol. Behav. 2008. Vol. 94. P. 187–197.Issemann I., Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators // Nature. 1990. Vol. 347. P. 645–650.Issemann I., Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators // Nature. 1990. Vol. 347. P. 645–650.Aranda A., Pascual A. Nuclear hormone receptors and gene expression // Physiol. Rev. 2001. Vol. 81. P. 1269–1304.Aranda A., Pascual A. Nuclear hormone receptors and gene expression // Physiol. Rev. 2001. Vol. 81. P. 1269–1304.Kliewer S. A., Xu H. E., Lambert M. H. et al. Peroxisome proliferator-activated receptors: from gene to physiology // Recent. Prog. Horm. Res. 2001. Vol. 56. P. 239–263.Kliewer S. A., Xu H. E., Lambert M. H. et al. Peroxisome proliferator-activated receptors: from gene to physiology // Recent. Prog. Horm. Res. 2001. Vol. 56. P. 239–263.Nunn A. V., Bell J., Barter P. The integration of lipid-sensing and anti-inflammatory effects: how the PPARs play a role in metabolic balance // Nuclear Recept. 2007. Vol. 5, N 1.Nunn A. V., Bell J., Barter P. The integration of lipid-sensing and anti-inflammatory effects: how the PPARs play a role in metabolic balance // Nuclear Recept. 2007. Vol. 5, N 1.Escher P., Braissant O., Basu-Modak S. et al. Rat PPAR: quantitative analysis in adult rat tissues and regulation in fasting and refeeding // Endocrinolology. 2001. Vol. 142. P. 4195–4202.Escher P., Braissant O., Basu-Modak S. et al. Rat PPAR: quantitative analysis in adult rat tissues and regulation in fasting and refeeding // Endocrinolology. 2001. Vol. 142. P. 4195–4202.Fredenrich A., Grimaldi P. A. PPAR delta: an uncompletely known nuclear receptor // Diabetes Metab. 2005. Vol. 31. P. 23–27.Fredenrich A., Grimaldi P. A. PPAR delta: an uncompletely known nuclear receptor // Diabetes Metab. 2005. Vol. 31. P. 23–27.Душкин М. И. Содержание PPAR, LXR и RXR и ДНК-связывающая активность PPAR в макрофагах в динамике воспаления у мышей / М. И. Душкин [и др.] // Бюл. эксперим. биологии и медицины. – 2009. – Т. 147. – С. 317–321.Душкин М. И. Содержание PPAR, LXR и RXR и ДНК-связывающая активность PPAR в макрофагах в динамике воспаления у мышей / М. И. Душкин [и др.] // Бюл. эксперим. биологии и медицины. – 2009. – Т. 147. – С. 317–321.Душкин М. И. Влияние агонистов PPARα и γ и LXR на содержание ядерных гормональных рецепторов PPARα, LXR и RXR в макрофагах и TNFα в крови мышей при остром воспалении / М. И. Душкин, М. И. Часовских, О. М. Хощенко // Цитокины и воспаление.– 2008. – Т. 7 (3). – С. 9–13.Душкин М. И. Влияние агонистов PPARα и γ и LXR на содержание ядерных гормональных рецепторов PPARα, LXR и RXR в макрофагах и TNFα в крови мышей при остром воспалении / М. И. Душкин, М. И. Часовских, О. М. Хощенко // Цитокины и воспаление.– 2008. – Т. 7 (3). – С. 9–13.Посохова Е. Н. Cинтез липидов в макрофагах при воспалении in vivo: влияние агонистов рецепторов, активирующих пролиферацию пероксисом-α и γ и ретиноидных Х рецепторов / Е. Н. Посохова [и др.] // Биохимия. – 2008. – Т. 73 (2). – С. 364–374.Посохова Е. Н. Cинтез липидов в макрофагах при воспалении in vivo: влияние агонистов рецепторов, активирующих пролиферацию пероксисом-α и γ и ретиноидных Х рецепторов / Е. Н. Посохова [и др.] // Биохимия. – 2008. – Т. 73 (2). – С. 364–374.Khovidhunkit W., Kim M.-S., Memon R. A. et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host // J. Lipid Res. 2004. Vol. 45. P. 1169–1196.Khovidhunkit W., Kim M.-S., Memon R. A. et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host // J. Lipid Res. 2004. Vol. 45. P. 1169–1196.Душкин М. И. Интеграция сигнальных путей регуляции липидного обмена и воспалительного ответа / М. И. Душкин, Е. Н. Кудинова, Я. Ш. Шварц // Цитокины и воспаление. – 2007. – Т. 6 (2). – С. 18–25.Душкин М. И. Интеграция сигнальных путей регуляции липидного обмена и воспалительного ответа / М. И. Душкин, Е. Н. Кудинова, Я. Ш. Шварц // Цитокины и воспаление. – 2007. – Т. 6 (2). – С. 18–25.Israelian-Konaraki Z., Reaven P. Peroxisome proliferator-activated receptor-alpha and atherosclerosis: from basic mechanisms to clinical implications // Cardiology. 2005. Vol. 103. P. 1–9.Israelian-Konaraki Z., Reaven P. Peroxisome proliferator-activated receptor-alpha and atherosclerosis: from basic mechanisms to clinical implications // Cardiology. 2005. Vol. 103. P. 1–9.Kubota N., Terauchi Y., Kubota T. et al. Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and -independent pathways // J. Biol. Chem. 2006. Vol. 281. P. 8748–8755.Kubota N., Terauchi Y., Kubota T. et al. Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and -independent pathways // J. Biol. Chem. 2006. Vol. 281. P. 8748–8755.Perissi V., Rosenfeld M. G. Controlling nuclear receptors: the circular logic of cofactor cycles // Nat. Rev. Mol. Cell. Biol. 2005. Vol. 6. P. 542–554.Perissi V., Rosenfeld M. G. Controlling nuclear receptors: the circular logic of cofactor cycles // Nat. Rev. Mol. Cell. Biol. 2005. Vol. 6. P. 542–554.Rochette-Egly C. Nuclear receptors: integration of multiple signaling pathways through phosphorylation // Cell. Signal. 2003. Vol. 15. P. 355–366.Rochette-Egly C. Nuclear receptors: integration of multiple signaling pathways through phosphorylation // Cell. Signal. 2003. Vol. 15. P. 355–366.Forman B. M., Chen J., Evans R. M. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for PPAR alpha and delta // Proc. Natl. Acad. Sci. USA. 1997. Vol. 94. P. 4312–4317.Forman B. M., Chen J., Evans R. M. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for PPAR alpha and delta // Proc. Natl. Acad. Sci. USA. 1997. Vol. 94. P. 4312–4317.Ricote M., Glass C. K. PPARs and molecular mechanisms of transrepression // Biochim. Biophys. Acta. 2007. Vol. 1771. P. 926–935.Ricote M., Glass C. K. PPARs and molecular mechanisms of transrepression // Biochim. Biophys. Acta. 2007. Vol. 1771. P. 926–935.Michalik L., Wahli W. PPARs mediate lipid signaling in inflammation and cancer // PPAR Research. 2008. Article ID 134059. P. 1–5.Michalik L., Wahli W. PPARs mediate lipid signaling in inflammation and cancer // PPAR Research. 2008. Article ID 134059. P. 1–5.Lefebvre P., Chinetti G., Fruchart J. C. et al. Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis // J. Clin. Invest. 2006. Vol. 116. P. 571–580.Lefebvre P., Chinetti G., Fruchart J. C. et al. Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis // J. Clin. Invest. 2006. Vol. 116. P. 571–580.Lee C. H., Olson P., Evans R. M. Minireview: lipid metabolism, metabolic diseases, and peroxisome proliferator-activated receptors // Endocrinology. 2003. Vol. 144. P. 2201–2207.Lee C. H., Olson P., Evans R. M. Minireview: lipid metabolism, metabolic diseases, and peroxisome proliferator-activated receptors // Endocrinology. 2003. Vol. 144. P. 2201–2207.Kersten S., Mandard S., Escher P. et al. The peroxisome proliferator-activated receptor alpha regulates amino acid metabolism // FASEB J. 2001. Vol. 15. P. 1971–1978.Kersten S., Mandard S., Escher P. et al. The peroxisome proliferator-activated receptor alpha regulates amino acid metabolism // FASEB J. 2001. Vol. 15. P. 1971–1978.Huang Z., Zhou X., Nicholson A. C. et al. Activation of peroxisome proliferator-activated receptor-alpha in mice induces expression of the hepatic low-density lipoprotein receptor // Br. J. Pharmacol. 2008. Vol. 155. P. 596–605.Huang Z., Zhou X., Nicholson A. C. et al. Activation of peroxisome proliferator-activated receptor-alpha in mice induces expression of the hepatic low-density lipoprotein receptor // Br. J. Pharmacol. 2008. Vol. 155. P. 596–605.Yaacob N. S., Kaderi M. A., Norazmi M. N. Differential transcriptional expression of PPARalpha, PPAR-gamma1, and PPARgamma2 in the peritoneal macrophages and T-cell subsets of non-obese diabetic mice // J. Clin. Immunol. 2009. Vol. 29. P. 595–602.Yaacob N. S., Kaderi M. A., Norazmi M. N. Differential transcriptional expression of PPARalpha, PPAR-gamma1, and PPARgamma2 in the peritoneal macrophages and T-cell subsets of non-obese diabetic mice // J. Clin. Immunol. 2009. Vol. 29. P. 595–602.Reddy J. K., Hashimoto T. Peroxisomal beta-oxidation and peroxisome proliferator-activated receptor alpha: an adaptive metabolic system // Annu. Rev. Nutr. 2001. Vol. 21. P. 193–230.Reddy J. K., Hashimoto T. Peroxisomal beta-oxidation and peroxisome proliferator-activated receptor alpha: an adaptive metabolic system // Annu. Rev. Nutr. 2001. Vol. 21. P. 193–230.Aoyama T., Peters J. M., Iritani N. et al. Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor alpha (PPARalpha) // J. Biol. Chem. 1998. Vol. 273. P. 5678–5684.Aoyama T., Peters J. M., Iritani N. et al. Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor alpha (PPARalpha) // J. Biol. Chem. 1998. Vol. 273. P. 5678–5684.Kersten S., Seydoux J., Peters J. M. et al. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting // J. Clin. Invest. 1999. Vol. 103. P. 1489–1498.Kersten S., Seydoux J., Peters J. M. et al. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting // J. Clin. Invest. 1999. Vol. 103. P. 1489–1498.Guerre-Millo M., Rouault C., Poulain P. et al. PPAR-alpha-null mice are protected from high-fat diet-induced insulin resistance // Diabetes. 2001. Vol. 50. P. 2809–2814.Guerre-Millo M., Rouault C., Poulain P. et al. PPAR-alpha-null mice are protected from high-fat diet-induced insulin resistance // Diabetes. 2001. Vol. 50. P. 2809–2814.Kuipers I., van der Harst P., Navis G. et al. Nuclear hormone receptors as regulators of the renin-angioten-sin-aldosterone system // Hypertension. 2008. Vol. 51. P. 1442–1448.Kuipers I., van der Harst P., Navis G. et al. Nuclear hormone receptors as regulators of the renin-angioten-sin-aldosterone system // Hypertension. 2008. Vol. 51. P. 1442–1448.Yagil C., Yagil Y. Peroxisome proliferator-activated receptor alpha: friend or foe? // Hypertension. 2007. Vol. 50. P. 847–850.Yagil C., Yagil Y. Peroxisome proliferator-activated receptor alpha: friend or foe? // Hypertension. 2007. Vol. 50. P. 847–850.Tordjman K. M., Semenkovich C. F., Coleman T. et al. Absence of peroxisome proliferator-activated receptor-alpha abolishes hypertension and attenuates atherosclerosis in the Tsukuba hypertensive mouse // Hypertension. 2007. Vol. 50. P. 945–951.Tordjman K. M., Semenkovich C. F., Coleman T. et al. Absence of peroxisome proliferator-activated receptor-alpha abolishes hypertension and attenuates atherosclerosis in the Tsukuba hypertensive mouse // Hypertension. 2007. Vol. 50. P. 945–951.Tordjman K., Bernal-Mizrachi C., Zemany L. et al. PPARalpha deficiency reduces insulin resistance and atherosclerosis in apoE-null mice // J. Clin. Invest. 2001. Vol. 107. P. 1025–1034.Tordjman K., Bernal-Mizrachi C., Zemany L. et al. PPARalpha deficiency reduces insulin resistance and atherosclerosis in apoE-null mice // J. Clin. Invest. 2001. Vol. 107. P. 1025–1034.Pandey N. R., Renwick J., Misquith A. et al. Linoleic acidenriched phospholipids act through peroxisome proliferator-activated receptors alpha to stimulate hepatic apolipoprotein A-I secretion // Biochemistry. 2008. Vol. 47. P. 1579–1587.Pandey N. R., Renwick J., Misquith A. et al. Linoleic acidenriched phospholipids act through peroxisome proliferator-activated receptors alpha to stimulate hepatic apolipoprotein A-I secretion // Biochemistry. 2008. Vol. 47. P. 1579–1587.Sun Y., Alexander S. P., Garle M. J. et al. Cannabinoid activation of PPAR alpha; a novel neuroprotective mechanism // Br. J. Pharmacol. 2007. Vol. 152. P. 734–743.Sun Y., Alexander S. P., Garle M. J. et al. Cannabinoid activation of PPAR alpha; a novel neuroprotective mechanism // Br. J. Pharmacol. 2007. Vol. 152. P. 734–743.Gaetani S., Kaye W. H., Cuomo V. et al. Role of endocannabinoids and their analogues in obesity and eating disorders // Eat Weight Disord. 2008. Vol. 13. P. E42–E48.Gaetani S., Kaye W. H., Cuomo V. et al. Role of endocannabinoids and their analogues in obesity and eating disorders // Eat Weight Disord. 2008. Vol. 13. P. E42–E48.Thabuis C., Tissot-Favre D., Bezelgues J. B. et al. Biological functions and metabolism of oleoylethanolamide // Lipids. 2008. Vol. 43. P. 887–894.Thabuis C., Tissot-Favre D., Bezelgues J. B. et al. Biological functions and metabolism of oleoylethanolamide // Lipids. 2008. Vol. 43. P. 887–894.Zhu Y., Qi C., Korenberg J. R. et al. Structural organization of mouse peroxisome proliferator-activated receptor gamma (mPPAR gamma) gene: alternative promoter use and different splicing yield two mPPAR gamma isoforms // Proc. Natl. Acad. Sci. USA. 1995. Vol. 92. P. 7921–7925.Zhu Y., Qi C., Korenberg J. R. et al. Structural organization of mouse peroxisome proliferator-activated receptor gamma (mPPAR gamma) gene: alternative promoter use and different splicing yield two mPPAR gamma isoforms // Proc. Natl. Acad. Sci. USA. 1995. Vol. 92. P. 7921–7925.Evans R. M., Barish G. D., Wang Y. X. PPARs and the complex journey to obesity // Nat. Med. 2004. Vol. 10. P. 355–361.Evans R. M., Barish G. D., Wang Y. X. PPARs and the complex journey to obesity // Nat. Med. 2004. Vol. 10. P. 355–361.Ranowala S. M., Lazar M. A. Peroxisome proliferator-activated receptor gamma in diabetes and metabolism // Trends Pharmacol. Sci. 2004. Vol. 25. P. 331–336.Ranowala S. M., Lazar M. A. Peroxisome proliferator-activated receptor gamma in diabetes and metabolism // Trends Pharmacol. Sci. 2004. Vol. 25. P. 331–336.Yki-Jarvinen H. Thiozolidinediones // N. Engl. J. Med. 2004. Vol. 351. P. 1106–1118.Yki-Jarvinen H. Thiozolidinediones // N. Engl. J. Med. 2004. Vol. 351. P. 1106–1118.Staels B., Fruchart J.-C. Terapeutic roles of peroxisome proliferator-activated receptor agonists // Diabetes. 2005. Vol. 54. P. 2460–2470.Staels B., Fruchart J.-C. Terapeutic roles of peroxisome proliferator-activated receptor agonists // Diabetes. 2005. Vol. 54. P. 2460–2470.Iwaki M., Matsuda M., Maeda N. Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors // Diabetes. 2003. Vol. 52. P. 1655–1663.Iwaki M., Matsuda M., Maeda N. Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors // Diabetes. 2003. Vol. 52. P. 1655–1663.Todorov V. T., Desch M., Schmitt-Nilson N. et al. Peroxisome proliferator-activated receptor-gamma is involved in the control of renin gene expression // Hypertension. 2007. Vol. 50. P. 939–944.Todorov V. T., Desch M., Schmitt-Nilson N. et al. Peroxisome proliferator-activated receptor-gamma is involved in the control of renin gene expression // Hypertension. 2007. Vol. 50. P. 939–944.Savage D. B., Tan G. D., Acerini C. L. et al. Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma // Diabetes. 2003. Vol. 52. P. 910–917.Savage D. B., Tan G. D., Acerini C. L. et al. Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma // Diabetes. 2003. Vol. 52. P. 910–917.Ringseis R., Gahler S., Eder K. Conjugated linoleic acid isomers inhibit platelet-derived growth factor-induced NF-kappaB transactivation and collagen formation in human vascular smooth muscle cells // Eur. J. Nutr. 2008. Vol. 47. P. 59–67.Ringseis R., Gahler S., Eder K. Conjugated linoleic acid isomers inhibit platelet-derived growth factor-induced NF-kappaB transactivation and collagen formation in human vascular smooth muscle cells // Eur. J. Nutr. 2008. Vol. 47. P. 59–67.Aas V., Rokling-Andersen M. H., Kase E. T. et al. Eicosapentaenoic acid (20:5 n-3) increases fatty acid and glucose uptake in cultured human skeletal muscle cells // J. Lipid Res. 2006. Vol. 47. Р. 366–374.Aas V., Rokling-Andersen M. H., Kase E. T. et al. Eicosapentaenoic acid (20:5 n-3) increases fatty acid and glucose uptake in cultured human skeletal muscle cells // J. Lipid Res. 2006. Vol. 47. Р. 366–374.Kliewer S. A., Lenhard J. M., Willson T. M. et al. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation // Cell. 1995. Vol. 83. P. 813–819.Kliewer S. A., Lenhard J. M., Willson T. M. et al. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation // Cell. 1995. Vol. 83. P. 813–819.Shibata T., Kondo M., Osawa T. et al. 15-deoxy-delta 12, 14-prostaglandin J2. A prostaglandin D2 metabolite generated during inflammatory processes // J. Biol. Chem. 2002. Vol. 277. P. 10459–10466.Shibata T., Kondo M., Osawa T. et al. 15-deoxy-delta 12, 14-prostaglandin J2. A prostaglandin D2 metabolite generated during inflammatory processes // J. Biol. Chem. 2002. Vol. 277. P. 10459–10466.Waku T., Shiraki T., Oyama T. et al. Structural insight into PPARgamma activation through covalent modification with endogenous fatty acids // J. Mol. Biol. 2009. Vol. 385 (1). P. 188–199.Waku T., Shiraki T., Oyama T. et al. Structural insight into PPARgamma activation through covalent modification with endogenous fatty acids // J. Mol. Biol. 2009. Vol. 385 (1). P. 188–199.Trostchansky A., Rubbo H. Nitrated fatty acids: mechanisms of formation, chemical characterization, and biological properties // Free Radic. Biol. Med. 2008. Vol. 44. P. 1887–1896.Trostchansky A., Rubbo H. Nitrated fatty acids: mechanisms of formation, chemical characterization, and biological properties // Free Radic. Biol. Med. 2008. Vol. 44. P. 1887–1896.Li Y., Zhang J., Schopfer F. J. et al. Molecular recognition of nitrated fatty acids by PPAR gamma // Nat. Struct. Mol. Biol. 2008. Vol. 15. P. 865–867.Li Y., Zhang J., Schopfer F. J. et al. Molecular recognition of nitrated fatty acids by PPAR gamma // Nat. Struct. Mol. Biol. 2008. Vol. 15. P. 865–867.Villacorta L., Schopfer F. J., Zhang J. et al. PPAR-gamma and its ligands: therapeutic implications in cardiovascular disease // Clin. Sci. (Lond). 2009. Vol. 116. P. 205–218.Villacorta L., Schopfer F. J., Zhang J. et al. PPAR-gamma and its ligands: therapeutic implications in cardiovascular disease // Clin. Sci. (Lond). 2009. Vol. 116. P. 205–218.Barak Y., Liao D., He W. et al. Effects of peroxisome proliferator activated receptor delta on placentation, adiposity, and colorectal cancer // Proc. Natl. Acad. Sci. USA. 2002. Vol. 99. P. 879–887.Barak Y., Liao D., He W. et al. Effects of peroxisome proliferator activated receptor delta on placentation, adiposity, and colorectal cancer // Proc. Natl. Acad. Sci. USA. 2002. Vol. 99. P. 879–887.Wang Y. X., Lee C. H., Tiep S. Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity // Cell. 2003. Vol. 113. P. 159–170.Wang Y. X., Lee C. H., Tiep S. Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity // Cell. 2003. Vol. 113. P. 159–170.Tanaka T., Yamamoto J., Iwasaki S. et al. Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome // Proc. Natl. Acad. Sci. USA. 2003. Vol. 100. P. 15924–15929.Tanaka T., Yamamoto J., Iwasaki S. et al. Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome // Proc. Natl. Acad. Sci. USA. 2003. Vol. 100. P. 15924–15929.Luquet S., Lopez-Soriano J., Holst D. Roles of peroxisome proliferator-activated receptor delta (PPARdelta) in the control of fatty acid catabolism. A new target for the treatment of metabolic syndrome // Biochimie. 2004. Vol. 86. P. 833–837.Luquet S., Lopez-Soriano J., Holst D. Roles of peroxisome proliferator-activated receptor delta (PPARdelta) in the control of fatty acid catabolism. A new target for the treatment of metabolic syndrome // Biochimie. 2004. Vol. 86. P. 833–837.Sprecher D. L., Massien C., Pearce G. et al. Triglyceride: high-density lipoprotein cholesterol effects in healthy subjects administered a peroxisome proliferator activated receptor-delta agonist // Arterioscler. Thromb. Vasc. Biol. 2007. Vol. 27. P. 359–365.Sprecher D. L., Massien C., Pearce G. et al. Triglyceride: high-density lipoprotein cholesterol effects in healthy subjects administered a peroxisome proliferator activated receptor-delta agonist // Arterioscler. Thromb. Vasc. Biol. 2007. Vol. 27. P. 359–365.Pette D., Staron R. S. Miosin isoforms, muscle fiber types and transformation // Microsc. Res. Tech. 2000. Vol. 50. P. 500–509.Pette D., Staron R. S. Miosin isoforms, muscle fiber types and transformation // Microsc. Res. Tech. 2000. Vol. 50. P. 500–509.Braissant O., Foufelle F., Scotto C. et al. Differencial expression PPARs: tissues of PPAR-alpha, -beta and -gamma in adult rat // Endocrinology. 1996. Vol. 137. P. 354–366.Braissant O., Foufelle F., Scotto C. et al. Differencial expression PPARs: tissues of PPAR-alpha, -beta and -gamma in adult rat // Endocrinology. 1996. Vol. 137. P. 354–366.Wang Y. X., Zhang C. L., Yu R. T. et al. Regulation of muscle fiber and running endurance by PPARdelta // PloS Biol. 2004. Vol. 2. P. e294.Wang Y. X., Zhang C. L., Yu R. T. et al. Regulation of muscle fiber and running endurance by PPARdelta // PloS Biol. 2004. Vol. 2. P. e294.Cheng L., Ding G., Qin Q. et al. Cardiomiocyte-restricted PPAR delta deletion perturbs myocardial fatty acid oxidation and leads to cardiomyopathy // Nat. Med. 2004. Vol. 10. P. 1245–1250.Cheng L., Ding G., Qin Q. et al. Cardiomiocyte-restricted PPAR delta deletion perturbs myocardial fatty acid oxidation and leads to cardiomyopathy // Nat. Med. 2004. Vol. 10. P. 1245–1250.Luquet S., Lopez-Soriano J., Holst D. et al. Peroxisome proliferator-activated receptor delta con-trols muscle development and oxidative capability // FASEB J. 2003. Vol. 17. P. 2299–2301.Luquet S., Lopez-Soriano J., Holst D. et al. Peroxisome proliferator-activated receptor delta con-trols muscle development and oxidative capability // FASEB J. 2003. Vol. 17. P. 2299–2301.Mohoney D. J., Parise G., Melov S. et al. Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise // FASEB J. 2005. Vol. 19. P. 1498–1500.Mohoney D. J., Parise G., Melov S. et al. Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise // FASEB J. 2005. Vol. 19. P. 1498–1500.Watt M. J., Southgate R. J., Holmes A. G. et al. Suppression of plasma free fatty acids upregulates peroxisome proliferator-activated receptor (PPAR) alpha and delta and PPAR coactivator 1 alpha in human skeletal muscle, but not lipid regulatory genes // J. Mol. Endocrinol. 2004. Vol. 33. P. 533–544.Watt M. J., Southgate R. J., Holmes A. G. et al. Suppression of plasma free fatty acids upregulates peroxisome proliferator-activated receptor (PPAR) alpha and delta and PPAR coactivator 1 alpha in human skeletal muscle, but not lipid regulatory genes // J. Mol. Endocrinol. 2004. Vol. 33. P. 533–544.Planavila A., Rodriguez-Calvo R., Jove M. et al. Peroxisome proliferator-activated receptor beta/delta activation inhibits hypertrophy in neonatal rat cardiomyocytes // Cardivasc. Res. 2005. Vol. 65. P. 832–841.Planavila A., Rodriguez-Calvo R., Jove M. et al. Peroxisome proliferator-activated receptor beta/delta activation inhibits hypertrophy in neonatal rat cardiomyocytes // Cardivasc. Res. 2005. Vol. 65. P. 832–841.Xu H. E., Lambert M. H., Montana V. G. et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors // Mol. Cell. 1999. Vol. 3. P. 397–403.Xu H. E., Lambert M. H., Montana V. G. et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors // Mol. Cell. 1999. Vol. 3. P. 397–403.Chawla A., Lee C. H., Barak Y. et al. PPARdelta is a very low-density lipoprotein sensor in macrophages // Proc. Natl. Acad. Sci. USA. 2003. Vol. 100. P. 1268–1273.Chawla A., Lee C. H., Barak Y. et al. PPARdelta is a very low-density lipoprotein sensor in macrophages // Proc. Natl. Acad. Sci. USA. 2003. Vol. 100. P. 1268–1273.Black P. H. The inflammatory response is an integral part of the stress response: implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X // Brain Behav. Immunol. 2003. Vol. 17. P. 350–364.Black P. H. The inflammatory response is an integral part of the stress response: implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X // Brain Behav. Immunol. 2003. Vol. 17. P. 350–364.Ellins E., Halcox J., Donald A. et al. Arterial stiffness and inflammatory response to psychophysiological stress // Brain Behav. Immun. 2008. Vol. 22. P. 941–948.Ellins E., Halcox J., Donald A. et al. Arterial stiffness and inflammatory response to psychophysiological stress // Brain Behav. Immun. 2008. Vol. 22. P. 941–948.Seematter G., Binnert C., Martin J. L. et al. Relationship between stress, inflammation and metabolism // Curr. Opin. Clin. Nutr. Metab. Care. 2004. Vol. 7. P. 169–173.Seematter G., Binnert C., Martin J. L. et al. Relationship between stress, inflammation and metabolism // Curr. Opin. Clin. Nutr. Metab. Care. 2004. Vol. 7. P. 169–173.Tracey K. J. The inflammatory reflex // Nature. 2002. Vol. 420. P. 853–859.Tracey K. J. The inflammatory reflex // Nature. 2002. Vol. 420. P. 853–859.Bierhaus A., Wolf J., Andrassy M. et al. A mechanism converting psychosocial stress into mononuclear cell activation // Proc. Natl. Acad. Sci. USA. 2003. Vol. 100. P. 1920–1925.Bierhaus A., Wolf J., Andrassy M. et al. A mechanism converting psychosocial stress into mononuclear cell activation // Proc. Natl. Acad. Sci. USA. 2003. Vol. 100. P. 1920–1925.Blair A. S., Hajduch E., Litherland G. J. et al. Regulation of glucose transport and glicogen synthesis in L6 muscle cells during oxidative stress. Evidence for cross-talk between the insulin and SAPK2/p38 mitogen-activated protein kinasessignaling pathways // J. Biol. Chem. 1999. Vol. 274. P. 36293–36299.Blair A. S., Hajduch E., Litherland G. J. et al. Regulation of glucose transport and glicogen synthesis in L6 muscle cells during oxidative stress. Evidence for cross-talk between the insulin and SAPK2/p38 mitogen-activated protein kinasessignaling pathways // J. Biol. Chem. 1999. Vol. 274. P. 36293–36299.Clerk A., Cullingford T. E., Fuller S. J. et al. Signaling pathways mediating cardiac myocyte gene expression in physiological and stress responses // J. Cell Physiol. 2007. Vol. 212. P. 311–322.Clerk A., Cullingford T. E., Fuller S. J. et al. Signaling pathways mediating cardiac myocyte gene expression in physiological and stress responses // J. Cell Physiol. 2007. Vol. 212. P. 311–322.Shoelson S. E., Lee J., Yuan M. Inflammation and IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance // Int. J. Obes. Relat. Metab. Disord. 2003. Vol. 27. Suppl. 3. P. S49–S52.Shoelson S. E., Lee J., Yuan M. Inflammation and IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance // Int. J. Obes. Relat. Metab. Disord. 2003. Vol. 27. Suppl. 3. P. S49–S52.Kopp E., Ghosh S. Inhibition of NF-kappa B by sodium salicylate and aspirin // Science. 1994. Vol. 265. P. 956–959.Kopp E., Ghosh S. Inhibition of NF-kappa B by sodium salicylate and aspirin // Science. 1994. Vol. 265. P. 956–959.Yuan M., Konstantopoulos N., Lee J. et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta // Science. 2001. Vol. 293. P. 1673–1677.Yuan M., Konstantopoulos N., Lee J. et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta // Science. 2001. Vol. 293. P. 1673–1677.Uysal K. T., Wiesbrock S. M., Marino M. W. et al. Protection from obesity-induced insulin resistence in mice laking TNF-alpha function // Nature. 1997. Vol. 389. P. 610–614.Uysal K. T., Wiesbrock S. M., Marino M. W. et al. Protection from obesity-induced insulin resistence in mice laking TNF-alpha function // Nature. 1997. Vol. 389. P. 610–614.Grant N., Hamer M., Steptoe A. Social isolation and stress-related cardiovascular, lipid, and cortisol responses // Ann. Behav. Med. 2009. Vol. 37. P. 29–37.Grant N., Hamer M., Steptoe A. Social isolation and stress-related cardiovascular, lipid, and cortisol responses // Ann. Behav. Med. 2009. Vol. 37. P. 29–37.Rosmond R., Dallman M. F., Bjorntorp P. Stress-related cortisol secretion in man: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities // J. Clin. Endocrinol. Metab. 1998. Vol. 83. P. 1853–1859.Rosmond R., Dallman M. F., Bjorntorp P. Stress-related cortisol secretion in man: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities // J. Clin. Endocrinol. Metab. 1998. Vol. 83. P. 1853–1859.Shively C. A., Register T. C., Clarkson T. B. Social stress, visceral obesity, and coronary artery atherosclerosis: product of a primate adaptation // Am. J. Primatol. 2009. Vol. 71. P. 742–751.Shively C. A., Register T. C., Clarkson T. B. Social stress, visceral obesity, and coronary artery atherosclerosis: product of a primate adaptation // Am. J. Primatol. 2009. Vol. 71. P. 742–751.Raikkonen K., Hautanen A., Kelitikangas-Jarvinen L. Association of stress and depression with regional fat distribution in healthy middle-aged men // J. Behav. Med. 1994. Vol. 17. P. 605–616.Raikkonen K., Hautanen A., Kelitikangas-Jarvinen L. Association of stress and depression with regional fat distribution in healthy middle-aged men // J. Behav. Med. 1994. Vol. 17. P. 605–616.Lissau I., Sorensen T. I. Parental neglect during child-hood and increased risk of obesity in young adulthood // Lancet. 1994. Vol. 343. P. 324–327.Lissau I., Sorensen T. I. Parental neglect during child-hood and increased risk of obesity in young adulthood // Lancet. 1994. Vol. 343. P. 324–327.Kanaka-Gantenbein C., Mastorakos G., Chrousos G. P. Endocrine-related causes and consequences of intrautering growth retardation // Ann. N. Y. Acad. Sci. 2003. Vol. 997. P. 150–157.Kanaka-Gantenbein C., Mastorakos G., Chrousos G. P. Endocrine-related causes and consequences of intrautering growth retardation // Ann. N. Y. Acad. Sci. 2003. Vol. 997. P. 150–157.Wu G., Brouckaert P., Olivecrova T. Rapid downregulation of adipose tissue lipoprotein lipase activity on food deprivation: evidence that TNF-alpha is involved // Am. J. Physiol. Endocrinol. Metab. 2004. Vol. 286. P. E711–E717.Wu G., Brouckaert P., Olivecrova T. Rapid downregulation of adipose tissue lipoprotein lipase activity on food deprivation: evidence that TNF-alpha is involved // Am. J. Physiol. Endocrinol. Metab. 2004. Vol. 286. P. E711–E717.Bashan N., Dorfman K., Tarnovscki T. et al. Mitogen-activated protein kinases, inhibitory-kappaB kinase, and insulin signaling in human omental versus subcutaneous adipose tissue in obesity // Endocrinology. 2007. Vol. 148. P. 2955–2962.Bashan N., Dorfman K., Tarnovscki T. et al. Mitogen-activated protein kinases, inhibitory-kappaB kinase, and insulin signaling in human omental versus subcutaneous adipose tissue in obesity // Endocrinology. 2007. Vol. 148. P. 2955–2962.Gao Z., Zhang X., Zuberi A. et al. Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3T3-L1 adipocites // Mol. Endocrinol. 2004. Vol. 18. P. 2024–2034.Gao Z., Zhang X., Zuberi A. et al. Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3T3-L1 adipocites // Mol. Endocrinol. 2004. Vol. 18. P. 2024–2034.Tripathy D., Mohanty P., Dhindsa S. et al. Elevaton of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects // Diabetes. 2003. Vol. 52. P. 2882–2887.Tripathy D., Mohanty P., Dhindsa S. et al. Elevaton of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects // Diabetes. 2003. Vol. 52. P. 2882–2887.Ajuwon K. M., Spurlock M. E. Palmitate activates the NF-kappaB transcription factors and induced IL-6 and TNF-alpha expression in 3T3-L1 adipocites // J. Nutr. 2005. Vol. 135. P. 1841–1846.Ajuwon K. M., Spurlock M. E. Palmitate activates the NF-kappaB transcription factors and induced IL-6 and TNF-alpha expression in 3T3-L1 adipocites // J. Nutr. 2005. Vol. 135. P. 1841–1846.Kim J. K., Kim Y. J., Fillmore J. J. et al. Prevention of fat-induced insulin resistance by salicylate // J. Clin. Invest. 2001. Vol. 108. P. 437–446.Kim J. K., Kim Y. J., Fillmore J. J. et al. Prevention of fat-induced insulin resistance by salicylate // J. Clin. Invest. 2001. Vol. 108. P. 437–446.Weisberg S. P., McCann D., Desai M. et al. Obesi ty is associated with macrophage accumulation in adi pose tissue // J. Clin. Invest. 2003. Vol. 112. P. 1796–1808.Weisberg S. P., McCann D., Desai M. et al. Obesi ty is associated with macrophage accumulation in adi pose tissue // J. Clin. Invest. 2003. Vol. 112. P. 1796–1808.Makowski L., Hotamisligil G. S. Fatty acid binding proteins – the evolucinary crossroads of inflammatory and metabolic responses // J. Nutr. 2004. Vol. 134. P. 2464S–2468S.Makowski L., Hotamisligil G. S. Fatty acid binding proteins – the evolucinary crossroads of inflammatory and metabolic responses // J. Nutr. 2004. Vol. 134. P. 2464S–2468S.Szelenyi J., Selmeczy Z., Brozik A. et al. Dual beta-adrenergic modulation in the immune system: stimulus-dependent effect of isoproterenol on MAPK activation and inflammatory mediator production in macrophages // Neurochem. Int. 2006. Vol. 49. P. 94–103.Szelenyi J., Selmeczy Z., Brozik A. et al. Dual beta-adrenergic modulation in the immune system: stimulus-dependent effect of isoproterenol on MAPK activation and inflammatory mediator production in macrophages // Neurochem. Int. 2006. Vol. 49. P. 94–103.Wellen K. E., Hotamisligil G. S. Inflammation, stress and diabetes // J. Clin. Invest. 2005. Vol. 115. P. 1111–1119.Wellen K. E., Hotamisligil G. S. Inflammation, stress and diabetes // J. Clin. Invest. 2005. Vol. 115. P. 1111–1119.Kloting N., Bluher M. Extended longevity and insulin signaling in adipose tissue // Exp. Gerontol. 2005. Vol. 40. P. 878–883.Kloting N., Bluher M. Extended longevity and insulin signaling in adipose tissue // Exp. Gerontol. 2005. Vol. 40. P. 878–883.Myers M. G., White M. F. The new elements of insulin signaling. Insulin receptor substrate-1 and proteins with SH2 domains // Diabetes. 1993. Vol. 42. P. 643–650.Myers M. G., White M. F. The new elements of insulin signaling. Insulin receptor substrate-1 and proteins with SH2 domains // Diabetes. 1993. Vol. 42. P. 643–650.Gual P., Le Marchand-Brustel Y., Tanti J. F. Positive and negative regulation of insulin signaling through IRS-1 phosphorylation // Biochimie. 2005. Vol. 87. P. 99–109.Gual P., Le Marchand-Brustel Y., Tanti J. F. Positive and negative regulation of insulin signaling through IRS-1 phosphorylation // Biochimie. 2005. Vol. 87. P. 99–109.Hotamisligil G. S., Peraldi P., Budavari A. et al. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNFalpha and obesity-induced insulin receptor substrate-1 // Science. 1996. Vol. 271. P. 665–668.Hotamisligil G. S., Peraldi P., Budavari A. et al. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNFalpha and obesity-induced insulin receptor substrate-1 // Science. 1996. Vol. 271. P. 665–668.Hotamisligil G. S. The role of TNFalpha and TNF receptors in obesity and insulin resistance // J. Intern. Med. 1999. Vol. 245. P. 621–625.Hotamisligil G. S. The role of TNFalpha and TNF receptors in obesity and insulin resistance // J. Intern. Med. 1999. Vol. 245. P. 621–625.Kyriakis J. M., Avruch J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation // Physiol. Rev. 2001. Vol. 81. P. 807–869.Kyriakis J. M., Avruch J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation // Physiol. Rev. 2001. Vol. 81. P. 807–869.Hirosumi J., Tuncman G., Chang L. et al. A central role for JNK in obesity and insulin resistance // Nature. 2002. Vol. 420. P. 333–336.Hirosumi J., Tuncman G., Chang L. et al. A central role for JNK in obesity and insulin resistance // Nature. 2002. Vol. 420. P. 333–336.Quinkler M., Troeger H., Eigendorff E. et al. Enhanced 11beta-hydroxysteroid dehydrogenase type 1 activity in stress adaptation in the guinea pig // J. Endocrinol. 2003. Vol. 176. P. 185–192.Quinkler M., Troeger H., Eigendorff E. et al. Enhanced 11beta-hydroxysteroid dehydrogenase type 1 activity in stress adaptation in the guinea pig // J. Endocrinol. 2003. Vol. 176. P. 185–192.Lemberger T., Saladin R., Vazquez M. et al. Expression of the peroxisome proliferator-activated receptor alpha gene is stimulated by stress and follows a diurnal rhythm // J. Biol. Chem. 1996. Vol. 271. P. 1764–1769.Lemberger T., Saladin R., Vazquez M. et al. Expression of the peroxisome proliferator-activated receptor alpha gene is stimulated by stress and follows a diurnal rhythm // J. Biol. Chem. 1996. Vol. 271. P. 1764–1769.Purnell J. Q., Kahn S. E., Samuels M. H. et al. Enhanced cortisol production rates, free cortisol, and 11beta-HSD-1 expression correlate with visceral fat and insulin resistance in men: effect of weight loss // Am. J. Physiol. Endocrinol. Metab. 2009. Vol. 296. P. E351–E357.Purnell J. Q., Kahn S. E., Samuels M. H. et al. Enhanced cortisol production rates, free cortisol, and 11beta-HSD-1 expression correlate with visceral fat and insulin resistance in men: effect of weight loss // Am. J. Physiol. Endocrinol. Metab. 2009. Vol. 296. P. E351–E357.Stimson R. H., Walker B. R. Glucocorticoids and 11beta-hydroxysteroid dehydrogenase type 1 in obesity and the metabolic syndrome // Minerva Endocrinol. 2007. Vol. 32. P. 141–159.Stimson R. H., Walker B. R. Glucocorticoids and 11beta-hydroxysteroid dehydrogenase type 1 in obesity and the metabolic syndrome // Minerva Endocrinol. 2007. Vol. 32. P. 141–159.Morton N. M., Paterson J. M., Masuzaki H. et al. Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11 beta-hydroxysteroid dehydrogenase type 1-deficient mice // Diabetes. 2004. Vol. 53. P. 931–938.Morton N. M., Paterson J. M., Masuzaki H. et al. Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11 beta-hydroxysteroid dehydrogenase type 1-deficient mice // Diabetes. 2004. Vol. 53. P. 931–938.Paterson J. M., Morton N. M., Fievet C. et al. Metabolic syndrome without obesity: Hepatic overexpression of 11β-hydroxysteroid dehydrogenase type 1 in transgenic mice // Proc. Natl. Acad. Sci. USA. 2004. Vol. 101. P. 7088–7093.Paterson J. M., Morton N. M., Fievet C. et al. Metabolic syndrome without obesity: Hepatic overexpression of 11β-hydroxysteroid dehydrogenase type 1 in transgenic mice // Proc. Natl. Acad. Sci. USA. 2004. Vol. 101. P. 7088–7093.Steineger H. H., Sorensen H. N., Tugwood J. D. et al. Dexamethasone and insulin demonstrate marked and opposite regulation of the steady-state mRNA level of the peroxisomal proliferator-activated receptor (PPAR) in hepatic cells. Hormonal modulation of fatty-acid-induced transcription // Eur. J. Biochem. 1994. Vol. 225. P. 967–974.Steineger H. H., Sorensen H. N., Tugwood J. D. et al. Dexamethasone and insulin demonstrate marked and opposite regulation of the steady-state mRNA level of the peroxisomal proliferator-activated receptor (PPAR) in hepatic cells. Hormonal modulation of fatty-acid-induced transcription // Eur. J. Biochem. 1994. Vol. 225. P. 967–974.Chakravarthy M. V., Pan Z., Zhu Y. et al. «New» hepatic fat activates PPARalpha to maintain glucose, lipid, and cholesterol homeostasis // Cell Metab. 2005. Vol. 1. P. 309–322.Chakravarthy M. V., Pan Z., Zhu Y. et al. «New» hepatic fat activates PPARalpha to maintain glucose, lipid, and cholesterol homeostasis // Cell Metab. 2005. Vol. 1. P. 309–322.Cha D. R., Han J. Y., Su D. M. et al. Peroxisome proliferator-activated receptor-alpha deficiency protects aged mice from insulin resistance induced by high-fat diet // Am. J. Nephrol. 2007. Vol. 27. P. 479–482.Cha D. R., Han J. Y., Su D. M. et al. Peroxisome proliferator-activated receptor-alpha deficiency protects aged mice from insulin resistance induced by high-fat diet // Am. J. Nephrol. 2007. Vol. 27. P. 479–482.Bernal-Mizrachi C., Weng S., Feng C. et al. Dexamethasone induction of hypertension and diabetes is PPAR-alpha dependent in LDL receptor-null mice // Nat. Med. 2003. Vol. 9. P. 1069–1075.Bernal-Mizrachi C., Weng S., Feng C. et al. Dexamethasone induction of hypertension and diabetes is PPAR-alpha dependent in LDL receptor-null mice // Nat. Med. 2003. Vol. 9. P. 1069–1075.Markel A. L., Redina O. E., Gilinsky M. A. Neuroendocrine profiling in inherited stress-induced arterial hypertension rat strain with stress-sensitive arterial hypertension // J. Endocrinol. 2007. Vol. 195. P. 439–450.Markel A. L., Redina O. E., Gilinsky M. A. Neuroendocrine profiling in inherited stress-induced arterial hypertension rat strain with stress-sensitive arterial hypertension // J. Endocrinol. 2007. Vol. 195. P. 439–450.Bernal-Mizrachi C., Xiaozhong L., Yin L. et al. An afferent vagal nerve pathway links hepatic PPARalpha activation to glucocorticoid-induced insulin resistance and hypertension // Cell Metab. 2007. Vol. 5. P. 91–102.Bernal-Mizrachi C., Xiaozhong L., Yin L. et al. An afferent vagal nerve pathway links hepatic PPARalpha activation to glucocorticoid-induced insulin resistance and hypertension // Cell Metab. 2007. Vol. 5. P. 91–102.Gonzalez-Yanes C., Serrano A., Bermudez-Silva F. J. et al. Oleylethanolamide impairs glucose tolerance and inhibits insulin-stimulated glucose uptake in rat adipocytes through p38 and JNK MAPK pathways // Am. J. Physiol. Endocrinol. Metab. 2005. Vol. 289. P. 923–929.Gonzalez-Yanes C., Serrano A., Bermudez-Silva F. J. et al. Oleylethanolamide impairs glucose tolerance and inhibits insulin-stimulated glucose uptake in rat adipocytes through p38 and JNK MAPK pathways // Am. J. Physiol. Endocrinol. Metab. 2005. Vol. 289. P. 923–929.Subramanian S., DeRosa M. A., Bernal-Mizrachi C. et al. PPARalpha activation elevates blood pressure and does not correct glucocorticoid-induced insulin resistance in humans // Am. J. Physiol. Endocrinol. Metab. 2006. Vol. 291. P. E1365–E1371.Subramanian S., DeRosa M. A., Bernal-Mizrachi C. et al. PPARalpha activation elevates blood pressure and does not correct glucocorticoid-induced insulin resistance in humans // Am. J. Physiol. Endocrinol. Metab. 2006. Vol. 291. P. E1365–E1371.Chakravarthy M. V., Zhu Y., Lopez M. et al. Brain fatty acid synthase activates PPARalpha to maintain energy homeostasis // J. Clin. Invest. 2007. Vol. 117. P. 2539–2552.Chakravarthy M. V., Zhu Y., Lopez M. et al. Brain fatty acid synthase activates PPARalpha to maintain energy homeostasis // J. Clin. Invest. 2007. Vol. 117. P. 2539–2552.Lane M. D., Wolfgang M., Cha S. H., Dai Y. Regulation of food intake and energy expenditure by hypothalamic malonyl-CoA // Int. J. Obes. (Lond). 2008. Vol. 32. (Suppl. 4). P. S49–S54.Lane M. D., Wolfgang M., Cha S. H., Dai Y. Regulation of food intake and energy expenditure by hypothalamic malonyl-CoA // Int. J. Obes. (Lond). 2008. Vol. 32. (Suppl. 4). P. S49–S54.Chakravarthy M. V., Lodhi I. J., Yin L. et al. Identification of a physiologically relevant endogenous ligand for PPARalpha in liver // Cell. 2009. Vol. 138. P. 476–488.Chakravarthy M. V., Lodhi I. J., Yin L. et al. Identification of a physiologically relevant endogenous ligand for PPARalpha in liver // Cell. 2009. Vol. 138. P. 476–488.Loftus T. M., Jaworsky D. E., Frehywot G. L. et al. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors // Science. 2000. Vol. 288. P. 2379–2381.Loftus T. M., Jaworsky D. E., Frehywot G. L. et al. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors // Science. 2000. Vol. 288. P. 2379–2381.Cha S. H., Hu Z., Chohnan S. et al. Inhibition of hypothalamic fatty acid synthase triggers rapid activation of fatty acid oxidation in skeletal muscle // Proc. Natl. Acad. Sci. USA. 2005. Vol. 102. P. 14557–14562.Cha S. H., Hu Z., Chohnan S. et al. Inhibition of hypothalamic fatty acid synthase triggers rapid activation of fatty acid oxidation in skeletal muscle // Proc. Natl. Acad. Sci. USA. 2005. Vol. 102. P. 14557–14562.Cha S. H., Rodgers J. T., Puigserver P. et al. Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle: role of PGC1alpha // Proc. Natl. Acad. Sci. USA. 2006. Vol. 103. P. 15410–15415.Cha S. H., Rodgers J. T., Puigserver P. et al. Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle: role of PGC1alpha // Proc. Natl. Acad. Sci. USA. 2006. Vol. 103. P. 15410–15415.Gonzales L. W., Ballard P. L., Gonzales J. Glucocorticoid and cAMP increase fatty acid synthetase mRNA in human fetal lung explants // Biochim. Biophys. Acta. 1994. Vol. 1215. P. 49–58.Gonzales L. W., Ballard P. L., Gonzales J. Glucocorticoid and cAMP increase fatty acid synthetase mRNA in human fetal lung explants // Biochim. Biophys. Acta. 1994. Vol. 1215. P. 49–58.Dudek S. M., Semenkovich C. F. Essential amino acids regulate fatty acid synthase expression through an uncharged transfer RNA-dependent mechanism // J. Biol. Chem. 1995. Vol. 270. P. 29323–29329.Dudek S. M., Semenkovich C. F. Essential amino acids regulate fatty acid synthase expression through an uncharged transfer RNA-dependent mechanism // J. Biol. Chem. 1995. Vol. 270. P. 29323–29329.Fukuda H., Iritani N., Sugimoto T. et al. Transcriptional regulation of fatty acid synthase gene by insulin / glucose, polyunsaturated fatty acid and leptin in hepatocytes and adipocytes in normal and genetically obese rats // Eur. J. Biochem. 1999. Vol. 260. P. 505–511.Fukuda H., Iritani N., Sugimoto T. et al. Transcriptional regulation of fatty acid synthase gene by insulin / glucose, polyunsaturated fatty acid and leptin in hepatocytes and adipocytes in normal and genetically obese rats // Eur. J. Biochem. 1999. Vol. 260. P. 505–511.Semenkovich C. F., Coleman T., Goforth R. Physiologic concentrations of glucose regulate fatty acid synthase activity in HepG2 cells by mediating fatty acid synthase mRNA stability // J. Biol. Chem. 1993. Vol. 268. P. 6961–6970.Semenkovich C. F., Coleman T., Goforth R. Physiologic concentrations of glucose regulate fatty acid synthase activity in HepG2 cells by mediating fatty acid synthase mRNA stability // J. Biol. Chem. 1993. Vol. 268. P. 6961–6970.Chakravarthy M. V., Zhu Y., Yin L. et al. Inactivation of hypothalamic FAS protects mice from diet-induced obesity and inflammation // J. Lipid Res. 2009. Vol. 50. P. 630–640.Chakravarthy M. V., Zhu Y., Yin L. et al. Inactivation of hypothalamic FAS protects mice from diet-induced obesity and inflammation // J. Lipid Res. 2009. Vol. 50. P. 630–640.Garcia-Bueno B., Madrigal J. L., Lizasoain I. et al. Peroxisome proliferator-activated receptor gamma activation decreases neuroinflammation in brain after stress in rats // Biol. Psychiatry. 2005. Vol. 57. P. 885–894.Garcia-Bueno B., Madrigal J. L., Lizasoain I. et al. Peroxisome proliferator-activated receptor gamma activation decreases neuroinflammation in brain after stress in rats // Biol. Psychiatry. 2005. Vol. 57. P. 885–894.Garcia-Bueno B., Madrigal J. L., Lizasoain I. et al. The anti-inflammatory prostaglandin 15d-PGJ2 decreases oxidative/nitrosative mediators in brain after acute stress in rats // Psychopharmacology (Berl.). 2005. Vol. 180. P. 513–522.Garcia-Bueno B., Madrigal J. L., Lizasoain I. et al. The anti-inflammatory prostaglandin 15d-PGJ2 decreases oxidative/nitrosative mediators in brain after acute stress in rats // Psychopharmacology (Berl.). 2005. Vol. 180. P. 513–522.Garcia-Bueno B., Madrigal J. L., Perez-Nievas B. G. et al. Stress mediators regulate brain prostaglandin synthesis and peroxisome proliferator-activated receptor-gamma activation after stress in rats // Endocrinology. 2008. Vol. 149. P. 1969–1978.Garcia-Bueno B., Madrigal J. L., Perez-Nievas B. G. et al. Stress mediators regulate brain prostaglandin synthesis and peroxisome proliferator-activated receptor-gamma activation after stress in rats // Endocrinology. 2008. Vol. 149. P. 1969–1978.She Q. M., Zhao J., Wang X. L. et al. Effect of dexamethasone on peroxisome proliferator activated receptor-gamma mRNA expression in 3T3-L1 adipocytes with the human recombinant adiponectin // Chin. Med. J. (Engl). 2007. Vol. 120. P. 155–158.She Q. M., Zhao J., Wang X. L. et al. Effect of dexamethasone on peroxisome proliferator activated receptor-gamma mRNA expression in 3T3-L1 adipocytes with the human recombinant adiponectin // Chin. Med. J. (Engl). 2007. Vol. 120. P. 155–158.Yang Y. K., Chen M., Clements R. H. et al. Human mesenteric adipose tissue plays unique role versus subcutaneous and omental fat in obesity related diabetes // Cell Physiol. Biochem. 2008. Vol. 22. P. 531–538.Yang Y. K., Chen M., Clements R. H. et al. Human mesenteric adipose tissue plays unique role versus subcutaneous and omental fat in obesity related diabetes // Cell Physiol. Biochem. 2008. Vol. 22. P. 531–538.Barish G. D., Narkar V. A., Evans R. M. PPARδ: a dagger in the heart of the metabolic syndrome // J. Clin. Invest. 2006. Vol. 116. P. 590–597.Barish G. D., Narkar V. A., Evans R. M. PPARδ: a dagger in the heart of the metabolic syndrome // J. Clin. Invest. 2006. Vol. 116. P. 590–597.Madrigal J. L., Kalinin S., Richardson J. C. et al. Neuroprotective actions of noradrenaline: effects on glutathione synthesis and activation of peroxisome proliferator activated receptor delta // J. Neurochem. 2007. Vol. 103. P. 2092–2101.Madrigal J. L., Kalinin S., Richardson J. C. et al. Neuroprotective actions of noradrenaline: effects on glutathione synthesis and activation of peroxisome proliferator activated receptor delta // J. Neurochem. 2007. Vol. 103. P. 2092–2101.Bechtold D. A. Energy-responsive timekeeping // J. Genet. 2008. Vol. 87. P. 447–458.Bechtold D. A. Energy-responsive timekeeping // J. Genet. 2008. Vol. 87. P. 447–458.Inoue I., Shinoda Y., Ikeda M. et al. CLOCK / BMAL1 is involved in lipid metabolism via transactivation of the peroxisome proliferator-activated receptor (PPAR) response element // J. Atheroscler. Thromb. 2005. Vol. 12. P. 169–174.Inoue I., Shinoda Y., Ikeda M. et al. CLOCK / BMAL1 is involved in lipid metabolism via transactivation of the peroxisome proliferator-activated receptor (PPAR) response element // J. Atheroscler. Thromb. 2005. Vol. 12. P. 169–174.Wang N., Yang G., Jia Z. et al. Vascular PPARgamma controls circadian variation in blood pressure and heart rate through Bmal1 // Cell Metab. 2008. Vol. 8. P. 482–491.Wang N., Yang G., Jia Z. et al. Vascular PPARgamma controls circadian variation in blood pressure and heart rate through Bmal1 // Cell Metab. 2008. Vol. 8. P. 482–491.Wang N., Symons J. D., Zhang H. et al. Distinct functions of vascular endothelial and smooth muscle PPARgamma in regulation of blood pressure and vascular tone // Toxicol. Pathol. 2009. Vol. 37. P. 21–27.Wang N., Symons J. D., Zhang H. et al. Distinct functions of vascular endothelial and smooth muscle PPARgamma in regulation of blood pressure and vascular tone // Toxicol. Pathol. 2009. Vol. 37. P. 21–27.Teboul M., Guillaumond F., Grechez-Cassiau A. et al. The nuclear hormone receptor family round the clock // Mol. Endocrinol. 2008. Vol. 22. P. 2573–2582.Teboul M., Guillaumond F., Grechez-Cassiau A. et al. The nuclear hormone receptor family round the clock // Mol. Endocrinol. 2008. Vol. 22. P. 2573–2582.Nakano S., Inada Y., Masuzaki H. et al. Bezafibrate regulates the expression and enzyme activity of 11beta-hydroxysteroid dehydrogenase type 1 in murine adipose tissue and 3T3-L1 adipocytes // Am. J. Physiol. Endocrinol. Metab. 2007. Vol. 292. P. E1213–E1222.Nakano S., Inada Y., Masuzaki H. et al. Bezafibrate regulates the expression and enzyme activity of 11beta-hydroxysteroid dehydrogenase type 1 in murine adipose tissue and 3T3-L1 adipocytes // Am. J. Physiol. Endocrinol. Metab. 2007. Vol. 292. P. E1213–E1222.Chen X., Li M., Sun W. et al. Peroxisome proliferator-activated receptor alpha agonist-induced down-regulation of hepatic glucocorticoid recep tor expression in SD rats // Biochem. Biophys. Res. Commun. 2008. Vol. 368. P. 865–870.Chen X., Li M., Sun W. et al. Peroxisome proliferator-activated receptor alpha agonist-induced down-regulation of hepatic glucocorticoid recep tor expression in SD rats // Biochem. Biophys. Res. Commun. 2008. Vol. 368. P. 865–870.Garcia-Bueno B., Caso J. R., Perez-Nievas B. G. et al. Effects of peroxisome proliferator-activated receptor gamma agonists on brain glucose and glutamate transporters after stress in rats // Neuropsychopharmacology. 2007. Vol. 32. P. 1251–1260.Garcia-Bueno B., Caso J. R., Perez-Nievas B. G. et al. Effects of peroxisome proliferator-activated receptor gamma agonists on brain glucose and glutamate transporters after stress in rats // Neuropsychopharmacology. 2007. Vol. 32. P. 1251–1260.Ponferrada A., Caso J. R., Alou L. et al. The role of PPARgamma on restoration of colonic homeostasis after experimental stress-induced inflammation and dysfunction // Gastroenterology. 2007. Vol. 132. P. 1791–1803.Ponferrada A., Caso J. R., Alou L. et al. The role of PPARgamma on restoration of colonic homeostasis after experimental stress-induced inflammation and dysfunction // Gastroenterology. 2007. Vol. 132. P. 1791–1803.Festuccia W. T., Oztezcan S., Laplante M. et al. Peroxisome proliferator-activated receptor-gamma-mediated positive energy balance in the rat is associated with reduced sympathetic drive to adipose tissues and thyroid status // Endocrinology. 2008. Vol. 149. P. 2121–2130.Festuccia W. T., Oztezcan S., Laplante M. et al. Peroxisome proliferator-activated receptor-gamma-mediated positive energy balance in the rat is associated with reduced sympathetic drive to adipose tissues and thyroid status // Endocrinology. 2008. Vol. 149. P. 2121–2130.Berthiaume M., Laplante M., Festuccia W. T. et al. Additive action of 11beta-HSD1 inhibition and PPAR-gamma agonism on hepatic steatosis and triglyceridemia in diet-induced obese rats // Int. J. Obes. (Lond). 2009. Vol. 33. P. 601–604.Berthiaume M., Laplante M., Festuccia W. T. et al. Additive action of 11beta-HSD1 inhibition and PPAR-gamma agonism on hepatic steatosis and triglyceridemia in diet-induced obese rats // Int. J. Obes. (Lond). 2009. Vol. 33. P. 601–604.Chen W., Wang L. L., Liu H. Y. et al. Peroxisome proliferator-activated receptor delta-agonist, GW501516, ameliorates insulin resistance, improves dyslipidaemia in monosodium L-glutamate metabolic syndrome mice // Basic Clin. Pharmacol. Toxicol. 2008. Vol. 103. P. 240–246.Chen W., Wang L. L., Liu H. Y. et al. Peroxisome proliferator-activated receptor delta-agonist, GW501516, ameliorates insulin resistance, improves dyslipidaemia in monosodium L-glutamate metabolic syndrome mice // Basic Clin. Pharmacol. Toxicol. 2008. Vol. 103. P. 240–246.Rubenstrunk A., Hanf R., Hum D. et al. Safety issues and prospects for future generations of PPAR modulators // Biochim. Biophys. Acta. 2007. Vol. 1771. P. 1065–1081.Rubenstrunk A., Hanf R., Hum D. et al. Safety issues and prospects for future generations of PPAR modulators // Biochim. Biophys. Acta. 2007. Vol. 1771. P. 1065–1081.Derosa G., Fogari E., D’Angelo A. et al. Metabolic effects of telmisartan and irbesartan in type 2 diabetic patients with metabolic syndrome treated with rosiglitazone // J. Clin. Pharmacol. Ther. 2007. Vol. 32. P. 261–268.Derosa G., Fogari E., D’Angelo A. et al. Metabolic effects of telmisartan and irbesartan in type 2 diabetic patients with metabolic syndrome treated with rosiglitazone // J. Clin. Pharmacol. Ther. 2007. Vol. 32. P. 261–268.Bichu P., Nistala R., Khan A. et al. Angiotensin receptor blockers for the reduction of proteinuria in diabetic patients with overt nephropathy: results from the AMADEO study // Vasc. Health Risk Manag. 2009. Vol. 5. P. 129–140.Bichu P., Nistala R., Khan A. et al. Angiotensin receptor blockers for the reduction of proteinuria in diabetic patients with overt nephropathy: results from the AMADEO study // Vasc. Health Risk Manag. 2009. Vol. 5. P. 129–140.Derosa G., Cicero A. F., D’Angelo A. et al. Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor-alpha // Hypertens. Res. 2006. Vol. 29. P. 849–856.Derosa G., Cicero A. F., D’Angelo A. et al. Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor-alpha // Hypertens. Res. 2006. Vol. 29. P. 849–856.Nakano R., Kurosaki E., Yoshida S. et al. Antagonism of peroxisome proliferator-activated receptor γ prevents high-fat diet-induced obesity in vivo // Biochem. Pharmacol. 2006. Vol. 72. P. 42–52.Nakano R., Kurosaki E., Yoshida S. et al. Antagonism of peroxisome proliferator-activated receptor γ prevents high-fat diet-induced obesity in vivo // Biochem. Pharmacol. 2006. Vol. 72. P. 42–52.Rieusset J., Touri F., Michalik L. et al. A new selective peroxisome proliferator-activated receptor γ antagonist with antiobesity and antidiabetic activity // Mol. Endocrinol. 2002. Vol. 16. P. 2628–2644.Rieusset J., Touri F., Michalik L. et al. A new selective peroxisome proliferator-activated receptor γ antagonist with antiobesity and antidiabetic activity // Mol. Endocrinol. 2002. Vol. 16. P. 2628–2644.Seber S., Ucak S., Basat O. et al. The effect of dual PPAR α/γ stimulation with combination of rosiglitazone and fenofibrate on metabolic parameters in type 2 diabetic patients // Diabetes Res. Clin. Pract. 2006. Vol. 71. P. 52–58.Seber S., Ucak S., Basat O. et al. The effect of dual PPAR α/γ stimulation with combination of rosiglitazone and fenofibrate on metabolic parameters in type 2 diabetic patients // Diabetes Res. Clin. Pract. 2006. Vol. 71. P. 52–58.Fievet C., Fruchart J.-C., Staels B. PPARα and PPARγ dual agonists for the treatment of type 2 diabetes and the metabolic syndrome // Curr. Opin. Pharmacol. 2006. Vol. 6. P. 606–614.Fievet C., Fruchart J.-C., Staels B. PPARα and PPARγ dual agonists for the treatment of type 2 diabetes and the metabolic syndrome // Curr. Opin. Pharmacol. 2006. Vol. 6. P. 606–614.Balakumar P., Rose M., Ganti S. S. et al. PPAR dual agonists: are they opening Pandora’s Box? // Pharmacol. Res. 2007. Vol. 56. P. 91–98.Balakumar P., Rose M., Ganti S. S. et al. PPAR dual agonists: are they opening Pandora’s Box? // Pharmacol. Res. 2007. Vol. 56. P. 91–98.Gonzalez I. C., Lamar J., Iradier F. et al. Design and synthesis of a novel class of dual PPARγ/δ agonists // Bioorg. Med. Chem. Lett. 2007. Vol. 17. P. 1052–1055.Gonzalez I. C., Lamar J., Iradier F. et al. Design and synthesis of a novel class of dual PPARγ/δ agonists // Bioorg. Med. Chem. Lett. 2007. Vol. 17. P. 1052–1055.Xu Y., Etgen G. J., Broderick C. L. et al. Design and synthesis of dual peroxisome proliferator-activated receptors gamma and delta agonists as novel euglycemic agents with a reduced weight gain profile // J. Med. Chem. 2006. Vol. 49. P. 5649–5652.Xu Y., Etgen G. J., Broderick C. L. et al. Design and synthesis of dual peroxisome proliferator-activated receptors gamma and delta agonists as novel euglycemic agents with a reduced weight gain profile // J. Med. Chem. 2006. Vol. 49. P. 5649–5652.Wallace J. M., Schwarz M., Coward P. et al. Effects of peroxisome proliferator-activated receptor alpha / delta agonists on HDL-cholesterol in vervet monkeys // J. Lipid Res. 2005. Vol. 46. P. 1009–1016.Wallace J. M., Schwarz M., Coward P. et al. Effects of peroxisome proliferator-activated receptor alpha / delta agonists on HDL-cholesterol in vervet monkeys // J. Lipid Res. 2005. Vol. 46. P. 1009–1016.Shen L., Zhang Y., Wang A. et al. Synthesis and identification of [1,2,4]thiadiazole derivatives as a new series of potent and orally active dual agonists of peroxisome proliferator-activated receptors α and δ // J. Med. Chem. 2007. Vol. 50. P. 3954–3963.Shen L., Zhang Y., Wang A. et al. Synthesis and identification of [1,2,4]thiadiazole derivatives as a new series of potent and orally active dual agonists of peroxisome proliferator-activated receptors α and δ // J. Med. Chem. 2007. Vol. 50. P. 3954–3963.Allen T., Zhang F., Moodie S. A. et al. Halofenate is a selective peroxisome proliferator-activated recep-tor γ modulator with antidiabetic activity // Diabetes. 2006. Vol. 55. P. 2523–2533.Allen T., Zhang F., Moodie S. A. et al. Halofenate is a selective peroxisome proliferator-activated recep-tor γ modulator with antidiabetic activity // Diabetes. 2006. Vol. 55. P. 2523–2533.Feldman P. L., Lambert M. H., Henke B. R. PPAR modulators and PPAR pan agonists for metabolic diseases: the next generation of drugs targeting peroxisome proliferator-activated receptors? // Curr. Top. Med. Chem. 2008. Vol. 8. P. 728–749.Feldman P. L., Lambert M. H., Henke B. R. PPAR modulators and PPAR pan agonists for metabolic diseases: the next generation of drugs targeting peroxisome proliferator-activated receptors? // Curr. Top. Med. Chem. 2008. Vol. 8. P. 728–749.Ramachandran U., Kumar R., Mittal A. Fine tuning of PPAR ligands for type 2 diabetes and metabolic syndrome // Mini Rev. Med. Chem. 2006. Vol. 6. P. 563–573.Ramachandran U., Kumar R., Mittal A. Fine tuning of PPAR ligands for type 2 diabetes and metabolic syndrome // Mini Rev. Med. Chem. 2006. Vol. 6. P. 563–573.Das U. N. Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules // Lipids Health Dis. 2008. Vol. 7. P. 37–43.Das U. N. Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules // Lipids Health Dis. 2008. Vol. 7. P. 37–43.Marion-Letellier R., Dechelotte P., Iacucci M. et al. Dietary modulation of peroxisome proliferator-activated receptor gamma // Gut. 2009. Vol. 58. P. 586–593.Marion-Letellier R., Dechelotte P., Iacucci M. et al. Dietary modulation of peroxisome proliferator-activated receptor gamma // Gut. 2009. Vol. 58. P. 586–593.Huang T. H., Teoh A. W., Lin B. L. et al. The role of herbal PPAR modulators in the treatment of cardiometabolic syndrome // Pharmacol. Res. 2009. Vol. 60. P. 195–206.Huang T. H., Teoh A. W., Lin B. L. et al. The role of herbal PPAR modulators in the treatment of cardiometabolic syndrome // Pharmacol. Res. 2009. Vol. 60. P. 195–206.Li Y., Qi Y., Huang T. et al. Pomegranate flower: a unique traditional antidiabetic medicine with dual PPAR-alpha/-gamma activator properties // Diabetes Obes. Metab. 2008. Vol. 10. P. 10–17.Li Y., Qi Y., Huang T. et al. Pomegranate flower: a unique traditional antidiabetic medicine with dual PPAR-alpha/-gamma activator properties // Diabetes Obes. Metab. 2008. Vol. 10. P. 10–17.Huang T. H., He L., Qin Q. et al. Salacia oblonga root decreases cardiac hypertrophy in Zucker diabetic fatty rats: inhibition of cardiac expression of angiotensin II type 1 receptor // Diabetes Obes. Metab. 2008. Vol. 10. P. 574–585.Huang T. H., He L., Qin Q. et al. Salacia oblonga root decreases cardiac hypertrophy in Zucker diabetic fatty rats: inhibition of cardiac expression of angiotensin II type 1 receptor // Diabetes Obes. Metab. 2008. Vol. 10. P. 574–585.Basu A., Penugonda K. Pomegranate juice: a heart-healthy fruit juice // Nutr. Rev. 2009 Vol. 67. P. 49–56.Basu A., Penugonda K. Pomegranate juice: a heart-healthy fruit juice // Nutr. Rev. 2009 Vol. 67. P. 49–56.

The authors declare that there are no conflicts of interest present.