aterosklerozАтеросклерозAteroscleroz2078-256X2949-3633НИИТПМ-филиал ИЦиГ СО РАН10.52727/2078-256X-2023-19-4-350-368ateroskleroz-1007Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESАтерогенные черты профиля жирных кислот мембран эритроцитов пациентов с жировой болезнью печени смешанного генезаAtherogenic features of the fatty acid profile of erythrocyte membranes of patients with fatty liver disease of mixed genesishttps://orcid.org/0000-0003-0077-3823КручининаМ. В.KruchininaM. V.

Маргарита Витальевна Кручинина - доктор медицинских наук, доцент, зав. лабораторией гастроэнтерологии, ведущий научный сотрудник лаборатории гастроэнтерологии НИИ терапии и профилактической медицины – филиала ИЦиГ СО РАН, профессор кафедры пропедевтики внутренних болезней ФГБОУ ВО «НГМУ» Минздрава Россиию.

630089, Новосибирск, ул. Бориса Богаткова, 175/1; 630091, Новосибирск, Красный просп., 52

Margarita V. Kruchinina, doctor of medical sciences, associate professor, head of the gastroenterology laboratory, leading researcher of the gastroenterology laboratory of the Research Institute of Internal and Preventive Medicine – Branch of ICIG SB RAS, professor of the department of propaedeutics of internal diseases of the NSMU.

175/1, Boris Bogatkov str., Novosibirsk, 630089; 52, Krasny Prospekt, Novosibirsk, 630091

kruchmargo@yandex.ruhttps://orcid.org/0000-0002-2610-1323БелковецА. В.BelkovetsA. V.

Анна Владимировна Белковец - доктор медицинских наук, доцент, старший научный сотрудник лаборатории гастроэнтерологии, заведующая клиникой НИИ терапии и профилактической медицины – филиала ИЦиГ СО РАН, профессор кафедры пропедевтики внутренних болезней ФГБОУ ВО «НГМУ» Минздрава России.

630089, Новосибирск, ул. Бориса Богаткова, 175/1; 630091, Новосибирск, Красный просп., 52

Anna V. Belkovets - doctor of medical sciences, associate professor, senior researcher at the laboratory of gastroenterology, head of the clinic of the Research Institute of Internal and Preventive Medicine – Branch of ICIG SB RAS, professor of the department of propaedeutics of internal diseases of the NSMU.

175/1, Boris Bogatkov str., Novosibirsk, 630089; 52, Krasny Prospekt, Novosibirsk, 630091

a_belkovets@bk.ruПаруликоваМ. В.ParulikovaM. V.

Марина Владимировна Паруликова - старший преподаватель Отдела образования, врач-гастроэнтеролог.

630089, Новосибирск, ул. Бориса Богаткова, 175/1

Marina V. Parulikova - senior lecturer of the department of education.

175/1, Boris Bogatkov str., Novosibirsk, 630089

m_parulikova@mail.ruhttps://orcid.org/0000-0001-9254-4192ГромовА. А.GromovA. A.

Андрей Александрович Громов - кандидат медицинских наук, старший научный сотрудник лаборатории клинических биохимических и гормональных исследований терапевтических заболеваний, руководитель Центра профилактики тромбозов.

630089, Новосибирск, ул. Бориса Богаткова, 175/1

Andrey A. Gromov - candidate of medical sciences, senior researcher at the laboratory of clinical biochemical and hormonal studies of therapeutic diseases, head of the thrombosis prevention center.

175/1, Boris Bogatkov str., Novosibirsk, 630089

gromov.center@rambler.ruНаучно-исследовательский институт терапии и профилактической медицины – филиал Федерального государственного бюджетного научного учреждения «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»; Федеральное государственное бюджетное образовательное учреждение высшего образования «Новосибирский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияResearch Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences; Federal State Budgetary Educational Institution of Higher Education «Novosibirsk State Medical University» of the Ministry of Health of the Russian FederationRussian FederationНаучно-исследовательский институт терапии и профилактической медицины – филиал Федерального государственного бюджетного научного учреждения «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»РоссияResearch Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of SciencesRussian Federation202315122023194350368Copyright © Кручинина М.В., Белковец А.В., Паруликова М.В., Громов А.А., 20232023Кручинина М.В., Белковец А.В., Паруликова М.В., Громов А.А.Kruchinina M.V., Belkovets A.V., Parulikova M.V., Gromov A.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://ateroskleroz.elpub.ru/jour/article/view/1007

Цель работы – изучить особенности профиля жирных кислот мембран эритроцитов пациентов с жировой болезнью печени (ЖБП) смешанного генеза (метаболический + алкогольный) с точки зрения атерогенных изменений.

Материал и методы

Материал и методы. Обследован 31 мужчина (возраст 50,6 ± 9,9 года) с ЖБП смешанного генеза, степень фиброза печени составляла 0-1 (FibroScan® 502 Echosens, Франция), и 28 лиц группы сравнения, сопоставимых по возрасту. Исследование состава жирных кислот (ЖК) мембран эритроцитов проведено с помощью газовой хроматографии/масс-спектрометрии – системы на основе трех квадруполей Agilent 7000B (США).

Результаты

Результаты. У пациентов с ЖБП смешанного генеза по сравнению со здоровыми лицами зарегистрирован более высокий уровень пальмитолеиновой (p = 0,03), пентадекановой (p = 0,05) ЖК, отношение содержания омега-6 и омега-3 полиненасыщенных жирных кислот (ПНЖК) (p = 0,03) и, напротив, более низкий – докозагексаеновой (p = 0,0002), суммарно эйкозапентаеновой и докозагексаеновой ЖК (p = 0,0007), всех омега-3 ПНЖК (p = 0,001) в мембранах эритроцитов. Отмечена тенденция к снижению содержания омега-3 эйкозапентаеновой ЖК и к повышению соотношения НЖК/ПНЖК при ЖБП смешанного генеза в отличие от лиц группы сравнения. Уровень отдельных ЖК обеспечил высокую диагностическую точность при дифференцировании пациентов с ЖБП смешанного генеза от здоровых лиц: пальмитолеиновой (9-С16:1) (площадь под ROC-кривой (AUC) 0,702, чувствительность 66,7 %, специфичность 69,6 %), докозагексаеновой (С22:6n-3) (AUC 0,795, чувствительность 77,3 %, специфичность 78,3 %), а также суммарно эйкозапентаеновой и докозегексаеновой (C20:5n-3 + С22:6n-3) (AUC 0,777, чувствительность 70,1 %, специфичность 82,6 %).

Заключение

Заключение. Выявленные особенности профиля ЖК мембран эритроцитов при ЖБП смешанного генеза – повышение содержание насыщенных, мононенасыщенных, омега-6 ПНЖК и снижение концентрации омега-3 ПНЖК – являются атерогенными. Продолжение исследований с точки зрения использования жирных кислот в качестве биомаркеров данной патологии и мишеней для терапевтических воздействий следует считать перспективным.

Aim of the study was to investigate the features of the fatty acid (FA) profile of erythrocyte membranes of patients with fatty liver disease (FLD) of mixed genesis (metabolic + alcoholic) from the point of view of atherogenic changes.

Material and methods

Material and methods. 31 men (50.6 ± 9.9 years old) with FLD of mixed genesis, the degree of liver fibrosis corresponded to 0-1 (FibroScan ® 502 Echosens, France), and 28 persons of the comparison group, comparable in age, were examined. The study of the composition of FAs of erythrocyte membranes was carried out using gas chromatography/mass spectrometry – a system based on three quadrupoles Agilent 7000B (USA).

Results

Results. Patients with FLD of mixed genesis had higher level of palmitoleic (p = 0.03), pentadecanoic (p = 0.05), omega-6 to omega-3 polyunsaturated fatter acids (PUFA) ratio (p = 0.03) and, conversely, lower level of docosahexaenoic (p = 0.0002), total content of eicosapentaenoic and docosahexaenoic FA (p = 0.0007), of all omega-3 PUFA (p = 0.001) in the membranes of erythrocytes compared to healthy persons. There are trends towards a decrease in the content of omega-3 eicosapentaenoic acid and an increase in the ratio of SFA/PUFA in patients with fibroids of mixed genesis in contrast to healthy individuals. The level of individual FA provided high diagnostic accuracy in differentiating patients with FLD of mixed genesis from healthy individuals: palmitoleic (9-C16:1) (area under ROC (AUC) 0.702, sensitivity 66.7 %, specificity 69.6 %), docosahexaenoic (C22:6n-3) (AUC 0.795, sensitivity 77.3 %, specificity 78.3 %), as well as the total content of eicosapentaenoic and docosegexaenoic FA (C20:5n-3 + C22:6n-3) (AUC 0.777, sensitivity 70.1 %, specificity 82.6 %).

Conclusions

Conclusions. The revealed features of the profile of erythrocyte membrane FA in FLD of mixed genesis – increase of saturated, monounsaturated, omega-6 PUFA content and reduce of omega-3 PUFA concentration are atherogenic. The continuation of research in terms of the use of FAs as biomarkers of this pathology and targets for therapeutic effects should be considered promising.

жировая болезнь печениметаболический генезалкогольный генезжирные кислотымембраны эритроцитоватерогенный характерfatty liver diseasemetabolic genesisalcoholic genesisfatty acidserythrocyte membranesatherogenic characterРабота выполнена по Государственному заданию в рамках бюджетных тем FWNR-2022-0024, FWNR-2023-0003The work was carried out according to the State task within the framework of the budget topics ASK-2022-0024, AZTEC-2023-0003ReferencesPimpin L., Cortez-Pinto H., Negro F., Corbould E., Lazarus J.V., Webber L., Sheron N.; EASL HEPAHEALTH Steering Committee. Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies. J. Hepatol., 2018; 69 (3): 718–735. doi: 10.1016/j.jhep.2018.05.011Pimpin L., Cortez-Pinto H., Negro F., Corbould E., Lazarus J.V., Webber L., Sheron N.; EASL HEPAHEALTH Steering Committee. Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies. J. Hepatol., 2018; 69 (3): 718–735. doi: 10.1016/j.jhep.2018.05.011Sarin S.K., Kumar M., Eslam M., George J., Al Mahtab M., Akbar S.M.F., Jia J., Tian Q., Aggarwal R., Muljono D.H., Omata M., Ooka Y., Han K.H., Lee H.W., Jafri W., Butt A.S., Chong C.H., Lim S.G., Pwu R.F., Chen D.S. Liver diseases in the Asia-Pacific region: a Lancet Gastroenterology & Hepatology Commission. The Lancet. Gastroenterology & hepatology, 2020; 5 (2): 167–228. https://doi.org/10.1016/S2468-1253(19)30342-5Sarin S.K., Kumar M., Eslam M., George J., Al Mahtab M., Akbar S.M.F., Jia J., Tian Q., Aggarwal R., Muljono D.H., Omata M., Ooka Y., Han K.H., Lee H.W., Jafri W., Butt A.S., Chong C.H., Lim S.G., Pwu R.F., Chen D.S. Liver diseases in the Asia-Pacific region: a Lancet Gastroenterology & Hepatology Commission. The Lancet. Gastroenterology & hepatology, 2020; 5 (2): 167–228. https://doi.org/10.1016/S2468-1253(19)30342-5Estes C., Razavi H., Loomba R., Younossi Z., Sanyal A.J. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology (Baltimore, Md.), 2018; 67 (1): 123–133. https://doi.org/10.1002/hep.29466Estes C., Razavi H., Loomba R., Younossi Z., Sanyal A.J. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology (Baltimore, Md.), 2018; 67 (1): 123–133. https://doi.org/10.1002/hep.29466Huang D.Q., Mathurin P., Cortez-Pinto H., Loomba R. Global epidemiology of alcohol-associated cirrhosis and HCC: trends, projections and risk factors. Nature Rev. Gastroenterology & Hepatology, 2023; 20 (1): 37–49. https://doi.org/10.1038/s41575-02200688-6Huang D.Q., Mathurin P., Cortez-Pinto H., Loomba R. Global epidemiology of alcohol-associated cirrhosis and HCC: trends, projections and risk factors. Nature Rev. Gastroenterology & Hepatology, 2023; 20 (1): 37–49. https://doi.org/10.1038/s41575-02200688-6Rehm J., Samokhvalov A.V., Shield K.D. Global burden of alcoholic liver diseases. J. Hepatol., 2013; 59 (1): 160–168. doi: 10.1016/j.jhep.2013.03.007Rehm J., Samokhvalov A.V., Shield K.D. Global burden of alcoholic liver diseases. J. Hepatol., 2013; 59 (1): 160–168. doi: 10.1016/j.jhep.2013.03.007Balmer M.L., Dufour J.F. Nicht-alkoholische Steatohepatitis – von NAFLD zu MAFLD [Non-alcoholic steatohepatitis – from NAFLD to MAFLD]. Ther. Umsch., 2011; 68 (4): 183–188. German. doi: 10.1024/0040-5930/a000148Balmer M.L., Dufour J.F. Nicht-alkoholische Steatohepatitis – von NAFLD zu MAFLD [Non-alcoholic steatohepatitis – from NAFLD to MAFLD]. Ther. Umsch., 2011; 68 (4): 183–188. German. doi: 10.1024/0040-5930/a000148Toh J.Z.K., Pan X.H., Tay P.W.L., Ng C.H., Yong J.N., Xiao J., Koh J.H., Tan E.Y., Tan E.X.X., Dan Y.Y., Loh P.H., Foo R., Chew N.W.S., Sanyal A.J., Muthiah M.D., Siddiqui M.S. A MetaAnalysis on the Global Prevalence, Risk factors and Screening of Coronary Heart Disease in Nonalcoholic Fatty Liver Disease. Clin. Gastroenterol. Hepatol., 2022; 20 (11): 2462–2473. e10. doi: 10.1016/j.cgh.2021.09.021.Toh J.Z.K., Pan X.H., Tay P.W.L., Ng C.H., Yong J.N., Xiao J., Koh J.H., Tan E.Y., Tan E.X.X., Dan Y.Y., Loh P.H., Foo R., Chew N.W.S., Sanyal A.J., Muthiah M.D., Siddiqui M.S. A MetaAnalysis on the Global Prevalence, Risk factors and Screening of Coronary Heart Disease in Nonalcoholic Fatty Liver Disease. Clin. Gastroenterol. Hepatol., 2022; 20 (11): 2462–2473. e10. doi: 10.1016/j.cgh.2021.09.021.Sung K.C., Ryu S., Lee J.Y., Lee S.H., Cheong E.S., Wild S.H., Byrne C.D. Fatty Liver, Insulin Resistance, and Obesity: Relationships With Increase in Coronary Artery Calcium Over Time. Clin. Cardiol., 2016; 39 (6): 321–328. https://doi.org/10.1002/clc.22529Sung K.C., Ryu S., Lee J.Y., Lee S.H., Cheong E.S., Wild S.H., Byrne C.D. Fatty Liver, Insulin Resistance, and Obesity: Relationships With Increase in Coronary Artery Calcium Over Time. Clin. Cardiol., 2016; 39 (6): 321–328. https://doi.org/10.1002/clc.22529Jacobs K., Brouha S., Bettencourt R., Barrett-Connor E., Sirlin C., Loomba R. Association of Nonalcoholic Fatty Liver Disease With Visceral Adiposity but Not Coronary Artery Calcification in the Elderly. Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association. 2016; 14 (9): 1337–1344.e3. https://doi.org/10.1016/j.cgh.2016.01.010Jacobs K., Brouha S., Bettencourt R., Barrett-Connor E., Sirlin C., Loomba R. Association of Nonalcoholic Fatty Liver Disease With Visceral Adiposity but Not Coronary Artery Calcification in the Elderly. Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association. 2016; 14 (9): 1337–1344.e3. https://doi.org/10.1016/j.cgh.2016.01.010Fracanzani A.L., Tiraboschi S., Pisano G., Consonni D., Baragetti A., Bertelli C., Norata D., Valenti L., Grigore L., Porzio M., Catapano A., Fargion S. Progression of carotid vascular damage and cardiovascular events in non-alcoholic fatty liver disease patients compared to the general population during 10 years of follow-up. Atherosclerosis, 2016; 246: 208–213. https://doi.org/10.1016/j.atherosclerosis.2016.01.016Fracanzani A.L., Tiraboschi S., Pisano G., Consonni D., Baragetti A., Bertelli C., Norata D., Valenti L., Grigore L., Porzio M., Catapano A., Fargion S. Progression of carotid vascular damage and cardiovascular events in non-alcoholic fatty liver disease patients compared to the general population during 10 years of follow-up. Atherosclerosis, 2016; 246: 208–213. https://doi.org/10.1016/j.atherosclerosis.2016.01.016Xu X., Lu L., Dong Q., Li X., Zhang N., Xin Y., Xuan S. Research advances in the relationship between nonalcoholic fatty liver disease and atherosclerosis. Lipids in Health and Disease, 2015; 14: 158. https://doi.org/10.1186/s12944-015-0141-zXu X., Lu L., Dong Q., Li X., Zhang N., Xin Y., Xuan S. Research advances in the relationship between nonalcoholic fatty liver disease and atherosclerosis. Lipids in Health and Disease, 2015; 14: 158. https://doi.org/10.1186/s12944-015-0141-zVilar C.P., Cotrim H.P., Florentino G.S., Barreto C.P., Florentino A.V., Bragagnoli G., Schwingel P.A. Association between nonalcoholic fatty liver disease and coronary artery disease. Revista da Associacao Medica Brasileira (1992), 2013; 59 (3): 290–297. https://doi.org/10.1016/j.ramb.2012.11.006Vilar C.P., Cotrim H.P., Florentino G.S., Barreto C.P., Florentino A.V., Bragagnoli G., Schwingel P.A. Association between nonalcoholic fatty liver disease and coronary artery disease. Revista da Associacao Medica Brasileira (1992), 2013; 59 (3): 290–297. https://doi.org/10.1016/j.ramb.2012.11.006Yu J., Marsh S., Hu J., Feng W., Wu C. The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background. Gastroenterol. Res. Pract, 2016; 2016: 2862173. doi: 10.1155/2016/2862173Yu J., Marsh S., Hu J., Feng W., Wu C. The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background. Gastroenterol. Res. Pract, 2016; 2016: 2862173. doi: 10.1155/2016/2862173Pafili K., Roden M. Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans. Mol. Metab., 2021; 50: 101122. doi: 10.1016/j.molmet.2020.101122Pafili K., Roden M. Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans. Mol. Metab., 2021; 50: 101122. doi: 10.1016/j.molmet.2020.101122Атеросклероз и дислипидемии. Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза. Российские рекомендации, VII пересмотр. 2020; 1 (38): 7–42. doi: 10.34687/2219-8202.JAD.2020.01.0002Atherosclerosis and dyslipidemia. Diagnosis and correction of lipid metabolism disorders for the prevention and treatment of atherosclerosis. Russian recommendations, VII revision. 2020; 1 (38): 7–42. doi: 10.34687/22198202.JAD.2020.01.0002 (In Russ.)Kotlyarov S., Kotlyarova A. Involvement of Fatty Acids and Their Metabolites in the Development of Inflammation in Atherosclerosis. Int. J. Mol. Sci., 2022; 23 (3): 1308. doi: 10.3390/ijms23031308Kotlyarov S., Kotlyarova A. Involvement of Fatty Acids and Their Metabolites in the Development of Inflammation in Atherosclerosis. Int. J. Mol. Sci., 2022; 23 (3): 1308. doi: 10.3390/ijms23031308Ravnskov U. The questionable role of saturated and polyunsaturated fatty acids in cardiovascular disease. J. Clin. Epidemiol., 1998; 51 (6): 443–460. doi: 10.1016/s0895-4356(98)00018-3Ravnskov U. The questionable role of saturated and polyunsaturated fatty acids in cardiovascular disease. J. Clin. Epidemiol., 1998; 51 (6): 443–460. doi: 10.1016/s0895-4356(98)00018-3Maki K.C., Dicklin M.R., Kirkpatrick C.F. Saturated fats and cardiovascular health: Current evidence and controversies. J. Clin. Lipidol., 2021; 15 (6): 765–772. doi: 10.1016/j.jacl.2021.09.049Maki K.C., Dicklin M.R., Kirkpatrick C.F. Saturated fats and cardiovascular health: Current evidence and controversies. J. Clin. Lipidol., 2021; 15 (6): 765–772. doi: 10.1016/j.jacl.2021.09.049Yagi S., Fukuda D., Aihara K.I., Akaike M., Shimabukuro M., Sata M. n-3 Polyunsaturated Fatty Acids: Promising Nutrients for Preventing Cardiovascular Disease. J. Atheroscler. Thromb., 2017; 24 (10): 999– 1010. doi: 10.5551/jat.RV17013Yagi S., Fukuda D., Aihara K.I., Akaike M., Shimabukuro M., Sata M. n-3 Polyunsaturated Fatty Acids: Promising Nutrients for Preventing Cardiovascular Disease. J. Atheroscler. Thromb., 2017; 24 (10): 999– 1010. doi: 10.5551/jat.RV17013Подымова С.Д. Болезни печени: Руководство для врачей. 5-е изд., перераб. и доп. М.: ООО «Медицинское информационное агентство», 2018. 984 с.Podymova S.D. Liver diseases: A guide for doctors. 5th edition, reprint. and additional. M.: LLC “Medical Information Agency”, 2018. 984 p. (in Russ.).Odriozola A., Santos-Laso A., Del Barrio M., Cabezas J., Iruzubieta P., Arias-Loste M.T., Rivas C., Duque J.C.R., Antón Á., Fábrega E., Crespo J. Fatty Liver Disease, Metabolism and Alcohol Interplay: A Comprehensive Review. Int. J. Mol. Sci., 2023; 24 (9): 7791. doi: 10.3390/ijms24097791Odriozola A., Santos-Laso A., Del Barrio M., Cabezas J., Iruzubieta P., Arias-Loste M.T., Rivas C., Duque J.C.R., Antón Á., Fábrega E., Crespo J. Fatty Liver Disease, Metabolism and Alcohol Interplay: A Comprehensive Review. Int. J. Mol. Sci., 2023; 24 (9): 7791. doi: 10.3390/ijms24097791Рекомендации экспертов ВНОК по диагностике и лечению метаболического синдрома (второй пересмотр). Кардиоваскуляр. терапия и профилактика, 2009: 6 (2).Recommendations of the VNOK experts on the diagnosis and treatment of metabolic syndrome (second revision). Cardiovascular. Therapy and Prevention, 2009: 6 (2) (In Russ.)Khang A.R., Lee H.W., Yi D., Kang Y.H., Son S.M. The fatty liver index, a simple and useful predictor of metabolic syndrome: analysis of the Korea National Health and Nutrition Examination Survey 2010-2011. Diabetes Metab. Syndr. Obes., 2019; 12: 181–190. doi: 10.2147/DMSO.S189544Khang A.R., Lee H.W., Yi D., Kang Y.H., Son S.M. The fatty liver index, a simple and useful predictor of metabolic syndrome: analysis of the Korea National Health and Nutrition Examination Survey 2010-2011. Diabetes Metab. Syndr. Obes., 2019; 12: 181–190. doi: 10.2147/DMSO.S189544Ивашкин В.Т., Маевская М.В., Павлов Ч.С., Тихонов И.Н., Широкова Е.Н., Буеверов А.О., Драпкина О.М., Шульпекова Ю.О., Цуканов В.В., Маммаев С.Н., Маев И.В., Пальгова Л.К. Клинические рекомендации по диагностике и лечению неалкогольной жировой болезни печени Российского общества по изучению печени и Российской гастроэнтерологической ассоциации. Рос. журн. гастроэнтерологии, гепатологии, колопроктологии, 2016; 26 (2): 24–42. https://doi.org/10.22416/1382-43762016-26-2-24-42Ivashkin V.T., Mayevskaya M.V., Pavlov Ch.S., Tikhonov I.N., Shirokova E.N., Bueverov A.O., Drapkina O.M., Shulpekova Yu.O., Tsukanov V.V., Mammaev S.N., Mayev I.V., Palgova L.K. Clinical recommendations for the diagnosis and treatment of non-alcoholic fatty liver diseases of the Russian Society for the Study of the Liver and the Russian Gastroenterological Association. Russian Journal of Gastroenterology, Hepatology, Coloproctology, 2016; 26 (2): 24–42. https://doi.org/10.22416/1382-43762016-26-2-24-42 (in Russ.).Arab L., Akbar J. Biomarkers and the measurement of fatty acids. Public. Health. Nutr., 2002; 5 (6A): 865–871. doi: 10.1079/phn2002391Arab L., Akbar J. Biomarkers and the measurement of fatty acids. Public. Health. Nutr., 2002; 5 (6A): 865–871. doi: 10.1079/phn2002391Кручинина М.В., Кручинин В.Н., Прудникова Я.И., Громов А.А., Шашков М.В., Соколова А.С. Исследование уровня жирных кислот мембран эритроцитов и сыворотки крови у пациентов с колоректальным раком г. Новосибирска. Успехи молекулярной онкологии, 2018; 5 (2): 50–61. doi: 10.17650/2313-805X-2018-5-2-50-61Kruchinina M.V., Kruchinin V.N., Prudnikova Ya.I., Gromov A.A., Shashkov M.V., Sokolova A.S. Investigation of the level of fatty acids of erythrocyte membranes and blood serum in patients with colorectal cancer in Novosibirsk. Advances in Molecular Oncology, 2018; 5 (2): 50–61. doi: 10.17650/2313-805X-2018-5-2-50-61. (In Russ.).Breiman L. Random Forests. Machine Learning., 2001; 45: 5–32. https://doi.org/10.1023/A:1010933404324.Breiman L. Random Forests. Machine Learning., 2001; 45: 5–32. https://doi.org/10.1023/A:1010933404324.Brunt E.M., Wong V.W., Nobili V., Day C.P., Sookoian S., Maher J.J., Bugianesi E., Sirlin C.B., Neuschwander-Tetri B.A., Rinella M.E. Nonalcoholic fatty liver disease. Nature reviews. Disease Primers, 2015; 1: 15080. https://doi.org/10.1038/nrdp.2015.80Brunt E.M., Wong V.W., Nobili V., Day C.P., Sookoian S., Maher J.J., Bugianesi E., Sirlin C.B., Neuschwander-Tetri B.A., Rinella M.E. Nonalcoholic fatty liver disease. Nature reviews. Disease Primers, 2015; 1: 15080. https://doi.org/10.1038/nrdp.2015.80Mitsuyoshi H., Yasui K., Harano Y., Endo M., Tsuji K., Minami M., Itoh Y., Okanoue T., Yoshikawa T. Analysis of hepatic genes involved in the metabolism of fatty acids and iron in nonalcoholic fatty liver disease. Hepatol. Res.: the Official Journal of the Japan Society of Hepatology, 2009; 39 (4): 366–373. https://doi.org/10.1111/j.1872-034X.2008.00464.xMitsuyoshi H., Yasui K., Harano Y., Endo M., Tsuji K., Minami M., Itoh Y., Okanoue T., Yoshikawa T. Analysis of hepatic genes involved in the metabolism of fatty acids and iron in nonalcoholic fatty liver disease. Hepatol. Res.: the Official Journal of the Japan Society of Hepatology, 2009; 39 (4): 366–373. https://doi.org/10.1111/j.1872-034X.2008.00464.xHe J., Lee J.H., Febbraio M., Xie W. The emerging roles of fatty acid translocase/CD36 and the aryl hydrocarbon receptor in fatty liver disease. Experimental Biol. and Med. (Maywood, N.J.), 2011; 236 (10): 1116–1121. https://doi.org/10.1258/ebm.2011.011128He J., Lee J.H., Febbraio M., Xie W. The emerging roles of fatty acid translocase/CD36 and the aryl hydrocarbon receptor in fatty liver disease. Experimental Biol. and Med. (Maywood, N.J.), 2011; 236 (10): 1116–1121. https://doi.org/10.1258/ebm.2011.011128Koliaki C., Szendroedi J., Kaul K., Jelenik T., Nowotny P., Jankowiak F., Herder C., Carstensen M., Krausch M., Knoefel W.T., Schlensak M., Roden M. Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis. Cell Metabolism, 2015; 21 (5): 739–746. https://doi.org/10.1016/j.cmet.2015.04.004Koliaki C., Szendroedi J., Kaul K., Jelenik T., Nowotny P., Jankowiak F., Herder C., Carstensen M., Krausch M., Knoefel W.T., Schlensak M., Roden M. Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis. Cell Metabolism, 2015; 21 (5): 739–746. https://doi.org/10.1016/j.cmet.2015.04.004Johnson E.S., Lindblom K.R., Robeson A., Stevens R.D., Ilkayeva O.R., Newgard C.B., Kornbluth S.,Andersen J.L. Metabolomic profiling reveals a role for caspase-2 in lipoapoptosis. The J. Biol. Chem., 2013; 288 (20): 14463–14475. https://doi.org/10.1074/jbc.M112.437210Johnson E.S., Lindblom K.R., Robeson A., Stevens R.D., Ilkayeva O.R., Newgard C.B., Kornbluth S.,Andersen J.L. Metabolomic profiling reveals a role for caspase-2 in lipoapoptosis. The J. Biol. Chem., 2013; 288 (20): 14463–14475. https://doi.org/10.1074/jbc.M112.437210Stienstra R., Saudale F., Duval C., Keshtkar S., Groener J. E., van Rooijen N., Staels B., Kersten S., Müller M. Kupffer cells promote hepatic steatosis via interleukin-1beta-dependent suppression of peroxisome proliferator-activated receptor alpha activity. Hepatology (Baltimore, Md.), 2010; 51 (2): 511–522. https://doi.org/10.1002/hep.23337Stienstra R., Saudale F., Duval C., Keshtkar S., Groener J. E., van Rooijen N., Staels B., Kersten S., Müller M. Kupffer cells promote hepatic steatosis via interleukin-1beta-dependent suppression of peroxisome proliferator-activated receptor alpha activity. Hepatology (Baltimore, Md.), 2010; 51 (2): 511–522. https://doi.org/10.1002/hep.23337Huby T., Gautier E.L. Immune cell-mediated features of non-alcoholic steatohepatitis. Nature reviews. Immunology, 2022; 22 (7): 429–443. https://doi.org/10.1038/s41577-021-00639-3Huby T., Gautier E.L. Immune cell-mediated features of non-alcoholic steatohepatitis. Nature reviews. Immunology, 2022; 22 (7): 429–443. https://doi.org/10.1038/s41577-021-00639-3Miura K., Yang L., van Rooijen N., Brenner D.A., Ohnishi H., Seki E. Toll-like receptor 2 and palmitic acid cooperatively contribute to the development of nonalcoholic steatohepatitis through inflammasome activation in mice. Hepatology (Baltimore, Md.), 2013; 57 (2): 577–589. https://doi.org/10.1002/hep.26081Miura K., Yang L., van Rooijen N., Brenner D.A., Ohnishi H., Seki E. Toll-like receptor 2 and palmitic acid cooperatively contribute to the development of nonalcoholic steatohepatitis through inflammasome activation in mice. Hepatology (Baltimore, Md.), 2013; 57 (2): 577–589. https://doi.org/10.1002/hep.26081Snodgrass R.G., Huang S., Choi I.W., Rutledge J.C., Hwang D.H. Inflammasome-mediated secretion of IL-1β in human monocytes through TLR2 activation; modulation by dietary fatty acids. J. Immunol (Baltimore, Md.: 1950), 2013; 191 (8): 4337–4347. https://doi.org/10.4049/jimmunol.1300298Snodgrass R.G., Huang S., Choi I.W., Rutledge J.C., Hwang D.H. Inflammasome-mediated secretion of IL-1β in human monocytes through TLR2 activation; modulation by dietary fatty acids. J. Immunol (Baltimore, Md.: 1950), 2013; 191 (8): 4337–4347. https://doi.org/10.4049/jimmunol.1300298Kim S.Y., Jeong J.M., Kim S.J., Seo W., Kim M.H., Choi W.M., Yoo W., Lee J.H., Shim Y.R., Yi H.S., Lee Y.S., Eun H.S., Lee B.S., Chun K., Kang S.J., Kim S.C., Gao B., Kunos G., Kim H.M., Jeong W.I. Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4-MD2 complex. Nat. Communicat., 2017; 8 (1): 2247. https://doi.org/10.1038/s41467-017-02325-2Kim S.Y., Jeong J.M., Kim S.J., Seo W., Kim M.H., Choi W.M., Yoo W., Lee J.H., Shim Y.R., Yi H.S., Lee Y.S., Eun H.S., Lee B.S., Chun K., Kang S.J., Kim S.C., Gao B., Kunos G., Kim H.M., Jeong W.I. Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4-MD2 complex. Nat. Communicat., 2017; 8 (1): 2247. https://doi.org/10.1038/s41467-017-02325-2Puri P., Baillie R.A., Wiest M.M., Mirshahi F., Choudhury J., Cheung O., Sargeant C., Contos M.J., Sanyal A.J. A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology, 2007; 46 (4): 1081–1090. doi: 10.1002/hep.21763Puri P., Baillie R.A., Wiest M.M., Mirshahi F., Choudhury J., Cheung O., Sargeant C., Contos M.J., Sanyal A.J. A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology, 2007; 46 (4): 1081–1090. doi: 10.1002/hep.21763Yamada K., Mizukoshi E., Sunagozaka H., Arai K., Yamashita T., Takeshita Y., Misu H., Takamura T., Kitamura S., Zen Y., Nakanuma Y., Honda M., Kaneko S. Characteristics of hepatic fatty acid compositions in patients with nonalcoholic steatohepatitis. Liver Int., 2015; 35 (2): 582–590. doi: 10.1111/liv.12685Yamada K., Mizukoshi E., Sunagozaka H., Arai K., Yamashita T., Takeshita Y., Misu H., Takamura T., Kitamura S., Zen Y., Nakanuma Y., Honda M., Kaneko S. Characteristics of hepatic fatty acid compositions in patients with nonalcoholic steatohepatitis. Liver Int., 2015; 35 (2): 582–590. doi: 10.1111/liv.12685Puri P., Wiest M.M., Cheung O., Mirshahi F., Sargeant C., Min H.K., Contos M.J., Sterling R.K., Fuchs M., Zhou H., Watkins S.M., Sanyal A.J. The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology, 2009; 50 (6): 1827–1838. doi: 10.1002/hep.23229Puri P., Wiest M.M., Cheung O., Mirshahi F., Sargeant C., Min H.K., Contos M.J., Sterling R.K., Fuchs M., Zhou H., Watkins S.M., Sanyal A.J. The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology, 2009; 50 (6): 1827–1838. doi: 10.1002/hep.23229Guo R., Chen L., Zhu J., Li J., Ding Q., Chang K., Han Q., Li S. Monounsaturated fatty acid-enriched olive oil exacerbates chronic alcohol-induced hepatic steatosis and liver injury in C57BL/6J mice. Food Funct., 2023; 14 (3): 1573–1583. doi: 10.1039/d2fo03323b.Guo R., Chen L., Zhu J., Li J., Ding Q., Chang K., Han Q., Li S. Monounsaturated fatty acid-enriched olive oil exacerbates chronic alcohol-induced hepatic steatosis and liver injury in C57BL/6J mice. Food Funct., 2023; 14 (3): 1573–1583. doi: 10.1039/d2fo03323b.Yoo W., Gjuka D., Stevenson H.L., Song X., Shen H., Yoo S.Y., Wang J., Fallon M., Ioannou G.N., Harrison S.A., Beretta L. Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid. PLoS One, 2017; 12 (12): e0189965. doi: 10.1371/journal.pone.0189965Yoo W., Gjuka D., Stevenson H.L., Song X., Shen H., Yoo S.Y., Wang J., Fallon M., Ioannou G.N., Harrison S.A., Beretta L. Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid. PLoS One, 2017; 12 (12): e0189965. doi: 10.1371/journal.pone.0189965Zhou Y., Orešič M., Leivonen M., Gopalacharyulu P., Hyysalo J., Arola J., Verrijken A., Francque S., van Gaal L., Hyötyläinen T., Yki-Järvinen H. Noninvasive Detection of Nonalcoholic Steatohepatitis Using Clinical Markers and Circulating Levels of Lipids and Metabolites. Clin. Gastroenterol. Hepatol., 2016; 14 (10): 1463–1472. e6. doi: 10.1016/j.cgh.2016.05.046Zhou Y., Orešič M., Leivonen M., Gopalacharyulu P., Hyysalo J., Arola J., Verrijken A., Francque S., van Gaal L., Hyötyläinen T., Yki-Järvinen H. Noninvasive Detection of Nonalcoholic Steatohepatitis Using Clinical Markers and Circulating Levels of Lipids and Metabolites. Clin. Gastroenterol. Hepatol., 2016; 14 (10): 1463–1472. e6. doi: 10.1016/j.cgh.2016.05.046Wang M., Zhang X., Ma L.J., Feng R.B., Yan C., Su H., He C., Kang J.X., Liu B., Wan J.B. Omega-3 polyunsaturated fatty acids ameliorate ethanol-induced adipose hyperlipolysis: A mechanism for hepatoprotective effect against alcoholic liver disease. Biochim. Biophys. Acta Mol. Basis. Dis., 2017; 1863 (12): 3190– 3201. doi: 10.1016/j.bbadis.2017.08.026Wang M., Zhang X., Ma L.J., Feng R.B., Yan C., Su H., He C., Kang J.X., Liu B., Wan J.B. Omega-3 polyunsaturated fatty acids ameliorate ethanol-induced adipose hyperlipolysis: A mechanism for hepatoprotective effect against alcoholic liver disease. Biochim. Biophys. Acta Mol. Basis. Dis., 2017; 1863 (12): 3190– 3201. doi: 10.1016/j.bbadis.2017.08.026Warner D.R., Liu H., Miller M.E., Ramsden C.E., Gao B., Feldstein A.E., Schuster S., McClain C.J., Kirpich I.A. Dietary Linoleic Acid and Its Oxidized Metabolites Exacerbate Liver Injury Caused by Ethanol via Induction of Hepatic Proinflammatory Response in Mice. Am. J. Pathol., 2017; 187 (10): 2232–2245. doi: 10.1016/j.ajpath.2017.06.008Warner D.R., Liu H., Miller M.E., Ramsden C.E., Gao B., Feldstein A.E., Schuster S., McClain C.J., Kirpich I.A. Dietary Linoleic Acid and Its Oxidized Metabolites Exacerbate Liver Injury Caused by Ethanol via Induction of Hepatic Proinflammatory Response in Mice. Am. J. Pathol., 2017; 187 (10): 2232–2245. doi: 10.1016/j.ajpath.2017.06.008Zhang W., Zhong W., Sun Q., Sun X., Zhou Z. Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice. Sci. Rep., 2017; 7 (1): 8976. doi: 10.1038/s41598-017-02759-0Zhang W., Zhong W., Sun Q., Sun X., Zhou Z. Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice. Sci. Rep., 2017; 7 (1): 8976. doi: 10.1038/s41598-017-02759-0Chei C.L., Yamagishi K., Kitamura A., Kiyama M., Sankai T., Okada T., Imano H., Ohira T., Cui R., Umesawa M., Muraki I., Tanigawa T., Sato S., Iso H. CIRCS Investigators. Serum Fatty Acid and Risk of Coronary Artery Disease – Circulatory Risk in Communities Study (CIRCS). Circ. J., 2018; 82 (12): 3013–3020. doi: 10.1253/circj.CJ-18-0240Chei C.L., Yamagishi K., Kitamura A., Kiyama M., Sankai T., Okada T., Imano H., Ohira T., Cui R., Umesawa M., Muraki I., Tanigawa T., Sato S., Iso H. CIRCS Investigators. Serum Fatty Acid and Risk of Coronary Artery Disease – Circulatory Risk in Communities Study (CIRCS). Circ. J., 2018; 82 (12): 3013–3020. doi: 10.1253/circj.CJ-18-0240Ragino Y.I., Shramko V.S., Stakhneva E.M., Chernyak E.I., Morozov S.V., Shakhtshneider E.V., Polonskaya Y.V., Shcherbakova L.V., Chernyavskiy A.M. Changes in the blood fatty-acid profile associated with oxidative-antioxidant disturbances in coronary atherosclerosis. J. Med. Biochem., 2020; 39 (1): 46–53. doi: 10.2478/jomb-2019-0010Ragino Y.I., Shramko V.S., Stakhneva E.M., Chernyak E.I., Morozov S.V., Shakhtshneider E.V., Polonskaya Y.V., Shcherbakova L.V., Chernyavskiy A.M. Changes in the blood fatty-acid profile associated with oxidative-antioxidant disturbances in coronary atherosclerosis. J. Med. Biochem., 2020; 39 (1): 46–53. doi: 10.2478/jomb-2019-0010Kritchevsky D., Tepper S.A., Czarnecki S.K., Sundram K. Red palm oil in experimental atherosclerosis. Asia Pac. J. Clin. Nutr., 2002; 11 Suppl 7: S433-S437. doi: 10.1046/j.1440-6047.11.s.7.5.xKritchevsky D., Tepper S.A., Czarnecki S.K., Sundram K. Red palm oil in experimental atherosclerosis. Asia Pac. J. Clin. Nutr., 2002; 11 Suppl 7: S433-S437. doi: 10.1046/j.1440-6047.11.s.7.5.xShramko V.S., Polonskaya Y.V., Kashtanova E.V., Stakhneva E.M., Ragino Y.I. The Short Overview on the Relevance of Fatty Acids for Human Cardiovascular Disorders. Biomolecules, 2020; 10 (8): 1127. doi: 10.3390/biom10081127Shramko V.S., Polonskaya Y.V., Kashtanova E.V., Stakhneva E.M., Ragino Y.I. The Short Overview on the Relevance of Fatty Acids for Human Cardiovascular Disorders. Biomolecules, 2020; 10 (8): 1127. doi: 10.3390/biom10081127Ebbesson S.O., Voruganti V.S., Higgins P.B., Fabsitz R.R., Ebbesson L.O., Laston S., Harris W.S., Kennish J., Umans B.D., Wang H., Devereux R.B., Okin P.M., Weissman N.J., MacCluer J.W., Umans J.G., Howard B.V. Fatty acids linked to cardiovascular mortality are associated with risk factors. Int. J. Circumpolar. Health, 2015; 74: 28055. doi: 10.3402/ijch.v74.28055Ebbesson S.O., Voruganti V.S., Higgins P.B., Fabsitz R.R., Ebbesson L.O., Laston S., Harris W.S., Kennish J., Umans B.D., Wang H., Devereux R.B., Okin P.M., Weissman N.J., MacCluer J.W., Umans J.G., Howard B.V. Fatty acids linked to cardiovascular mortality are associated with risk factors. Int. J. Circumpolar. Health, 2015; 74: 28055. doi: 10.3402/ijch.v74.28055Ding C., Wang L., Yao Y., Li C. Mechanism of the initial oxidation of monounsaturated fatty acids. Food Chem., 2022; 392: 133298. doi: 10.1016/j.foodchem.2022.133298Ding C., Wang L., Yao Y., Li C. Mechanism of the initial oxidation of monounsaturated fatty acids. Food Chem., 2022; 392: 133298. doi: 10.1016/j.foodchem.2022.133298Schwingshackl L., Hoffmann G. Monounsaturated Fatty Acids and Risk of Cardiovascular Disease: Synopsis of the Evidence Available from Systematic Reviews and Meta-Analyses. Nutrients, 2012; 4 (12): 1989– 2007. https://doi.org/10.3390/nu4121989Schwingshackl L., Hoffmann G. Monounsaturated Fatty Acids and Risk of Cardiovascular Disease: Synopsis of the Evidence Available from Systematic Reviews and Meta-Analyses. Nutrients, 2012; 4 (12): 1989– 2007. https://doi.org/10.3390/nu4121989Kotlyarov S., Kotlyarova A. Clinical significance of polyunsaturated fatty acids in the prevention of cardiovascular diseases. Front Nutr., 2022; 9: 998291. doi: 10.3389/fnut.2022.998291Kotlyarov S., Kotlyarova A. Clinical significance of polyunsaturated fatty acids in the prevention of cardiovascular diseases. Front Nutr., 2022; 9: 998291. doi: 10.3389/fnut.2022.998291Bäck M. Omega-3 fatty acids in atherosclerosis and coronary artery disease. Future Sci. OA., 2017; 3 (4): FSO236. doi: 10.4155/fsoa-2017-0067Bäck M. Omega-3 fatty acids in atherosclerosis and coronary artery disease. Future Sci. OA., 2017; 3 (4): FSO236. doi: 10.4155/fsoa-2017-0067Krupa-Kotara K., Grajek M., Wypych-Ślusarska A., Martynus-Depta S., Oleksiuk K., Głogowska-Ligus J., Szczepańska E., Słowiński J. Properties of Polyunsaturated Fatty Acids in Primary and Secondary Prevention of Cardiovascular Diseases in the View of Patients (Silesia, Poland). Nursing Reports, 2022; 12 (4): 980–992. https://doi.org/10.3390/nursrep12040094Krupa-Kotara K., Grajek M., Wypych-Ślusarska A., Martynus-Depta S., Oleksiuk K., Głogowska-Ligus J., Szczepańska E., Słowiński J. Properties of Polyunsaturated Fatty Acids in Primary and Secondary Prevention of Cardiovascular Diseases in the View of Patients (Silesia, Poland). Nursing Reports, 2022; 12 (4): 980–992. https://doi.org/10.3390/nursrep12040094Simonetto M., Infante M., Sacco R.L., Rundek T., Della-Morte D. A Novel Anti-Inflammatory Role of Omega-3 PUFAs in Prevention and Treatment of Atherosclerosis and Vascular Cognitive Impairment and Dementia. Nutrients, 2019; 11 (10): 2279. doi: 10.3390/nu11102279.Simonetto M., Infante M., Sacco R.L., Rundek T., Della-Morte D. A Novel Anti-Inflammatory Role of Omega-3 PUFAs in Prevention and Treatment of Atherosclerosis and Vascular Cognitive Impairment and Dementia. Nutrients, 2019; 11 (10): 2279. doi: 10.3390/nu11102279.Zehr K.R., Walker M.K. Omega-3 polyunsaturated fatty acids improve endothelial function in humans at risk for atherosclerosis: A review. Prostaglandins Other Lipid Mediat., 2018; 134: 131–140. doi: 10.1016/j.prostaglandins.2017.07.005Zehr K.R., Walker M.K. Omega-3 polyunsaturated fatty acids improve endothelial function in humans at risk for atherosclerosis: A review. Prostaglandins Other Lipid Mediat., 2018; 134: 131–140. doi: 10.1016/j.prostaglandins.2017.07.005Chang C.L., Deckelbaum R.J. Omega-3 fatty acids: mechanisms underlying ‘protective effects’ in atherosclerosis. Curr. Opin. Lipidol., 2013; 24 (4): 345–350. doi: 10.1097/MOL.0b013e3283616364Chang C.L., Deckelbaum R.J. Omega-3 fatty acids: mechanisms underlying ‘protective effects’ in atherosclerosis. Curr. Opin. Lipidol., 2013; 24 (4): 345–350. doi: 10.1097/MOL.0b013e3283616364Lee M.W., Park J.K., Hong J.W., Kim K.J., Shin D.Y., Ahn C.W., Song Y.D., Cho H.K., Park S.W., Lee E.J. Beneficial Effects of Omega-3 Fatty Acids on Low Density Lipoprotein Particle Size in Patients with Type 2 Diabetes Already under Statin Therapy. Diabetes Metab. J., 2013; 37 (3): 207–211. doi: 10.4093/dmj.2013.37.3.207Lee M.W., Park J.K., Hong J.W., Kim K.J., Shin D.Y., Ahn C.W., Song Y.D., Cho H.K., Park S.W., Lee E.J. Beneficial Effects of Omega-3 Fatty Acids on Low Density Lipoprotein Particle Size in Patients with Type 2 Diabetes Already under Statin Therapy. Diabetes Metab. J., 2013; 37 (3): 207–211. doi: 10.4093/dmj.2013.37.3.207John Chapman M., Preston Mason R. Cholesterol crystals and atherosclerotic plaque instability: Therapeutic potential of eicosapentaenoic acid. Pharmacol. Ther., 2022; 240: 108237. doi: 10.1016/j.pharmthera.2022.108237John Chapman M., Preston Mason R. Cholesterol crystals and atherosclerotic plaque instability: Therapeutic potential of eicosapentaenoic acid. Pharmacol. Ther., 2022; 240: 108237. doi: 10.1016/j.pharmthera.2022.108237Gao Z., Zhang D., Yan X., Shi H., Xian X. Effects of Polyunsaturated Fatty Acids on Coronary Atherosclerosis and Inflammation: A Systematic Review and Meta-Analysis. Front. Cardiovasc. Med., 2022; 9: 904250. doi: 10.3389/fcvm.2022.904250Gao Z., Zhang D., Yan X., Shi H., Xian X. Effects of Polyunsaturated Fatty Acids on Coronary Atherosclerosis and Inflammation: A Systematic Review and Meta-Analysis. Front. Cardiovasc. Med., 2022; 9: 904250. doi: 10.3389/fcvm.2022.904250Amano T., Matsubara T., Uetani T., Kato M., Kato B., Yoshida T., Harada K., Kumagai S., Kunimura A., Shinbo Y., Kitagawa K., Ishii H., Murohara T. Impact of omega-3 polyunsaturated fatty acids on coronary plaque instability: an integrated backscatter intravascular ultrasound study. Atherosclerosis, 2011; 218 (1): 110–116. doi: 10.1016/j.atherosclerosis.2011.05.030Amano T., Matsubara T., Uetani T., Kato M., Kato B., Yoshida T., Harada K., Kumagai S., Kunimura A., Shinbo Y., Kitagawa K., Ishii H., Murohara T. Impact of omega-3 polyunsaturated fatty acids on coronary plaque instability: an integrated backscatter intravascular ultrasound study. Atherosclerosis, 2011; 218 (1): 110–116. doi: 10.1016/j.atherosclerosis.2011.05.030Pertiwi K., Küpers L.K., de Goede J., Zock P.L., Kromhout D., Geleijnse J.M. Dietary and Circulating Long-Chain Omega-3 Polyunsaturated Fatty Acids and Mortality Risk After Myocardial Infarction: A Long-Term Follow-Up of the Alpha Omega Cohort. J. Am. Heart Assoc., 2021; 10 (23): e022617. doi: 10.1161/JAHA.121.022617Pertiwi K., Küpers L.K., de Goede J., Zock P.L., Kromhout D., Geleijnse J.M. Dietary and Circulating Long-Chain Omega-3 Polyunsaturated Fatty Acids and Mortality Risk After Myocardial Infarction: A Long-Term Follow-Up of the Alpha Omega Cohort. J. Am. Heart Assoc., 2021; 10 (23): e022617. doi: 10.1161/JAHA.121.022617Mariamenatu A.H., Abdu E.M. Overconsumption of Omega-6 Polyunsaturated Fatty Acids (PUFAs) versus Deficiency of Omega-3 PUFAs in Modern-Day Diets: The Disturbing Factor for Their “Balanced Antagonistic Metabolic Functions” in the Human Body. J. Lipids., 2021; 2021: 8848161. doi: 10.1155/2021/8848161.Mariamenatu A.H., Abdu E.M. Overconsumption of Omega-6 Polyunsaturated Fatty Acids (PUFAs) versus Deficiency of Omega-3 PUFAs in Modern-Day Diets: The Disturbing Factor for Their “Balanced Antagonistic Metabolic Functions” in the Human Body. J. Lipids., 2021; 2021: 8848161. doi: 10.1155/2021/8848161.Poreba M., Rostoff P., Siniarski A., Mostowik M., Golebiowska-Wiatrak R., Nessler J., Undas A., Gajos G. Relationship between polyunsaturated fatty acid composition in serum phospholipids, systemic lowgrade inflammation, and glycemic control in patients with type 2 diabetes and atherosclerotic cardiovascular disease. Cardiovasc. Diabetol., 2018; 17 (1): 29. doi: 10.1186/s12933-018-0672-5Poreba M., Rostoff P., Siniarski A., Mostowik M., Golebiowska-Wiatrak R., Nessler J., Undas A., Gajos G. Relationship between polyunsaturated fatty acid composition in serum phospholipids, systemic lowgrade inflammation, and glycemic control in patients with type 2 diabetes and atherosclerotic cardiovascular disease. Cardiovasc. Diabetol., 2018; 17 (1): 29. doi: 10.1186/s12933-018-0672-5Piper K., Garelnabi M. Eicosanoids: Atherosclerosis and cardiometabolic health. J. Clin. Transl. Endocrinol., 2020; 19: 100216. doi: 10.1016/j.jcte.2020.100216Piper K., Garelnabi M. Eicosanoids: Atherosclerosis and cardiometabolic health. J. Clin. Transl. Endocrinol., 2020; 19: 100216. doi: 10.1016/j.jcte.2020.100216Khandelwal S., Kelly L., Malik R., Prabhakaran D., Reddy S. Impact of omega-6 fatty acids on cardiovascular outcomes: A review. J. Preventive Cardiol., 2013; 2 (3): 325–336. PMID: 24955333; PMCID: PMC4062196.Khandelwal S., Kelly L., Malik R., Prabhakaran D., Reddy S. Impact of omega-6 fatty acids on cardiovascular outcomes: A review. J. Preventive Cardiol., 2013; 2 (3): 325–336. PMID: 24955333; PMCID: PMC4062196.

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