vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-26-88vavilov-5294Research ArticleФИЗИОЛОГИЧЕСКАЯ ГЕНЕТИКАPHYSIOLOGICAL GENETICSСпособность FGF21 снижать выраженность признаков неалкогольной жировой болезни печени у мышей зависит от пола и диетыThe ability of FGF21 to ameliorate signs of non-alcoholic fatty liver disease in mice depends on sex and dietБалыбинаН. Ю.BalybinaN. Yu.

Новосибирск

Novosibirsk

n.yu.balybina@gmail.comМакароваЕ. Н.MakarovaE. N.

Новосибирск

Novosibirsk

ЯковлеваТ. В.JakovlevaT. V.

Новосибирск

Novosibirsk

КазанцеваА. Ю.KazantsevaA. Yu.

Новосибирск

Novosibirsk

БажанН. М.BazhanN. M.

Новосибирск

Novosibirsk

Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian Federation202613102026306863874Copyright © Балыбина Н.Ю., Макарова Е.Н., Яковлева Т.В., Казанцева А.Ю., Бажан Н.М., 20262026Балыбина Н.Ю., Макарова Е.Н., Яковлева Т.В., Казанцева А.Ю., Бажан Н.М.Balybina N.Y., Makarova E.N., Jakovleva T.V., Kazantseva A.Y., Bazhan N.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/5294

Потребление высококалорийной пищи вызывает развитие ожирения и неалкогольной жировой болезни печени (НАЖБП). Патогенез НАЖБП зависит от состава диеты. Введение фактора роста фибробластов 21 (FGF21) ожиревшим мышам улучшает метаболизм и состояние печени, однако зависимость этого эффекта от пола и состава диеты еще не изучена. Цель нашего исследования – изучить влияние пола на состояние печени у мышей с алиментарным ожирением, вызванным диетами разного состава, и на способность FGF21 благотворно влиять на метаболическую функцию печени. Ожирение индуцировали у самцов и самок мышей C57BL/6J высокожирной диетой (ВЖД) или диетой кафетерия (ДК). После развития ожирения мышам вводили FGF21 (1 мг/кг, 7 дней) и оценивали морфофункциональное состояние печени и экспрессию генов, участвующих в процессах метаболизма жиров и углеводов, воспаления, фиброза и апоптоза в ткани печени. При содержании на ВЖД стеатоз печени у самок был менее выражен, чем у самцов. FGF21 не влиял на площадь липидных капель у особей обоих полов, но оказывал зависящее от пола влияние на экспрессию генов: у самок снижал экспрессию генов гликолиза и липогенеза, препятствуя отложению липидов, а у самцов – генов воспаления, апоптоза и фиброза, предотвращая переход стеатоза в стеатогепатит (воспаление печени). При содержании на ДК у мышей обоих полов развивался выраженный стеатоз. FGF21 снижал содержание липидов в печени независимо от пола. Однако только у самок FGF21 снижал экспрессию гена Cidec, участвующего в образовании липидных капель, и повышал количество апоптозных телец. У самцов эффект FGF21 на накопление липидов в печени, по-видимому, опосредован действием на другие ткани: жировую, мышечную и т. д. Таким образом, у мышей с ожирением половые различия в степени выраженности стеатоза печени зависели от типа диеты и проявлялись только на фоне ВЖД. Введение FGF21 приводило к уменьшению общей площади липидных капель в печени у мышей обоих полов только на фоне выраженного стеатоза, вызванного содержанием на ДК. Влияние FGF21 на экспрессию генов в печени зависело от пола как на фоне высокожирной диеты, так и на фоне диеты кафетерия.

Consumption of high-calorie food leads to the development of obesity and non-alcoholic fatty liver disease (NAFLD). The pathogenesis of NAFLD depends on the composition of the diet. Administration of fibroblast growth factor 21 (FGF21) to obese mice improves metabolism and liver condition; however, the dependence of this effect on sex and diet composition has not been studied. Objective: To investigate the influence of sex on liver condition in mice with diet-induced obesity caused by different diets and on the ability of FGF21 to beneficially affect liver function. Obesity was induced in male and female C57BL/6J mice using a high-fat diet (HFD) or a cafeteria diet (DCaf). After obesity development, mice were administered FGF21 (1 mg/kg for 7 days), and the morphofunctional state and gene expression in the liver were assessed. When maintained on an HFD, hepatic steatosis was less severe in females than in males. FGF21 did not affect the lipid droplet area in individuals of either sex but exerted a sex-dependent influence on gene expression: in females, it reduced the expression of glycolysis and lipogenesis genes, preventing lipid accumulation, while in males, it reduced the expression of inflammation, apoptosis, and fibrosis genes, preventing the transition from steatosis to steatohepatitis. When maintained on a DCaf, pronounced steatosis developed in mice of both sexes. FGF21 reduced liver lipid content regardless of sex. However, only in females did FGF21 reduce the expression of the Cidec gene involved in lipid droplet formation and increase the number of apoptotic bodies. In males, the effect of FGF21 on lipid accumulation in the liver appeared to be mediated by its action on other tissues. Thus, in obese mice, sex differences in the severity of hepatic steatosis depended on the diet type and were observed only against the background of HFD. Administration of FGF21 led to a reduction in the total area of lipid droplets in the liver in mice of both sexes only against the background of pronounced steatosis induced by the DCaf. The influence of FGF21 on gene expression in the liver was sex-dependent, both against the background of HFD and DCaf.

неалкогольная жировая болезнь печени (НАЖБП)стеатозFGF21диетаожирениеполовые различияпеченьnon-alcoholic fatty liver disease (NAFLD)steatosisFGF21dietobesitysex differencesliverThe work was carried out with the support of the Russian Science Foundation, project No. 23-15-00093ReferencesAlkhouri N., Carter-Kent C., Feldstein A.E. Apoptosis in nonalcoholic fatty liver disease: diagnostic and therapeutic implications. Expert Rev Gastroenterol Hepatol. 2011;5(2):201-212. doi 10.1586/egh.11.6Alkhouri N., Carter-Kent C., Feldstein A.E. Apoptosis in nonalcoholic fatty liver disease: diagnostic and therapeutic implications. Expert Rev Gastroenterol Hepatol. 2011;5(2):201-212. doi 10.1586/egh.11.6Asrih M., Jornayvaz F.R. Inflammation as a potential link between nonalcoholic fatty liver disease and insulin resistance. J Endocrinol. 2013;218(3):R25-R36. doi 10.1530/JOE-13-0201Asrih M., Jornayvaz F.R. Inflammation as a potential link between nonalcoholic fatty liver disease and insulin resistance. J Endocrinol. 2013;218(3):R25-R36. doi 10.1530/JOE-13-0201Bazhan N.M., Iakovleva T.V., Dubinina A.D., Makarova E.N. Impact of sex on the adaptation of adult mice to long consumption of sweetfat diet. Vavilov J Genet Breed. 2020;24(8):844-852. doi 10.18699/VJ20.682Bazhan N.M., Iakovleva T.V., Dubinina A.D., Makarova E.N. Impact of sex on the adaptation of adult mice to long consumption of sweetfat diet. Vavilov J Genet Breed. 2020;24(8):844-852. doi 10.18699/VJ20.682Bazhan N.М., Jakovleva T.V., Kazantseva A.Yu., Kostina N.E., Orlov P.E., Balybina N.Yu., Baranov K.О., Makarova E.N. Studying sex differences in responses to fibroblast growth factor 21 administration in obese mice consuming a sweet-fat diet. Vavilov J Genet Breed. 2023;27(4):333-341. doi 10.18699/VJGB-23-40Bazhan N.М., Jakovleva T.V., Kazantseva A.Yu., Kostina N.E., Orlov P.E., Balybina N.Yu., Baranov K.О., Makarova E.N. Studying sex differences in responses to fibroblast growth factor 21 administration in obese mice consuming a sweet-fat diet. Vavilov J Genet Breed. 2023;27(4):333-341. doi 10.18699/VJGB-23-40Boparai R.K., Arum O., Miquet J.G., Masternak M.M., Bartke A., Khardori R.K. Resistance to the beneficial metabolic effects and hepatic antioxidant defense actions of fibroblast growth factor 21 treatment in growth hormone-overexpressing transgenic mice. Int J Endocrinol. 2015;2015:282375. doi 10.1155/2015/282375Boparai R.K., Arum O., Miquet J.G., Masternak M.M., Bartke A., Khardori R.K. Resistance to the beneficial metabolic effects and hepatic antioxidant defense actions of fibroblast growth factor 21 treatment in growth hormone-overexpressing transgenic mice. Int J Endocrinol. 2015;2015:282375. doi 10.1155/2015/282375Buyukdere Y., Gulec A., Akyol A. Cafeteria diet increased adiposity in comparison to high fat diet in young male rats. PeerJ. 2019;7:e6656. doi 10.7717/peerj.6656Buyukdere Y., Gulec A., Akyol A. Cafeteria diet increased adiposity in comparison to high fat diet in young male rats. PeerJ. 2019;7:e6656. doi 10.7717/peerj.6656Chen X.L., Han Y.D., Wang H. Relations of hepatic steatosis with liver functions, inflammations, glucolipid metabolism in chronic hepatitis B patients. Eur Rev Med Pharmacol Sci. 2018;22(17):5640-5646. doi 10.26355/eurrev_201809_15830Chen X.L., Han Y.D., Wang H. Relations of hepatic steatosis with liver functions, inflammations, glucolipid metabolism in chronic hepatitis B patients. Eur Rev Med Pharmacol Sci. 2018;22(17):5640-5646. doi 10.26355/eurrev_201809_15830Fisher F.M., Maratos-Flier E. Understanding the physiology of FGF21. Annu Rev Physiol. 2016;78:223-241. doi 10.1146/annurev-physiol021115-105339Fisher F.M., Maratos-Flier E. Understanding the physiology of FGF21. Annu Rev Physiol. 2016;78:223-241. doi 10.1146/annurev-physiol021115-105339Friedman S.L., Neuschwander-Tetri B.A., Rinella M., Sanyal A.J. Mechanisms of NAFLD development and therapeutic strategies. Nat Med. 2018;24(7):908-922. doi 10.1038/s41591-018-0104-9Friedman S.L., Neuschwander-Tetri B.A., Rinella M., Sanyal A.J. Mechanisms of NAFLD development and therapeutic strategies. Nat Med. 2018;24(7):908-922. doi 10.1038/s41591-018-0104-9Gasparin F.R.S., Carreño F.O., Mewes J.M., Gilglioni E.H., Pagadigorria C.L.S., Natali M.R.M., Utsunomiya K.S., Constantin R.P., Ouchida A.T., Curti C., Gaemers I.C., Elferink R.P.J.O., Constantin J., Ishii-Iwamoto E.L. Sex differences in the development of hepatic steatosis in cafeteria diet-induced obesity in young mice. Biochim Biophys Acta Mol Basis Dis. 2018;1864(7):2495-2509. doi 10.1016/j.bbadis.2018.04.004Gasparin F.R.S., Carreño F.O., Mewes J.M., Gilglioni E.H., Pagadigorria C.L.S., Natali M.R.M., Utsunomiya K.S., Constantin R.P., Ouchida A.T., Curti C., Gaemers I.C., Elferink R.P.J.O., Constantin J., Ishii-Iwamoto E.L. Sex differences in the development of hepatic steatosis in cafeteria diet-induced obesity in young mice. Biochim Biophys Acta Mol Basis Dis. 2018;1864(7):2495-2509. doi 10.1016/j.bbadis.2018.04.004Haas J.T., Vonghia L., Mogilenko D.A., Verrijken A., Molendi-Coste O., Fleury S., Deprince A., … Driessen A., Lefebvre P., Staels B., Francque S., Dombrowicz D. Transcriptional network analysis implicates altered hepatic immune function in NASH development and resolution. Nat Metab. 2019;1(6):604-614. doi 10.1038/s42255-019-0076-1Haas J.T., Vonghia L., Mogilenko D.A., Verrijken A., Molendi-Coste O., Fleury S., Deprince A., … Driessen A., Lefebvre P., Staels B., Francque S., Dombrowicz D. Transcriptional network analysis implicates altered hepatic immune function in NASH development and resolution. Nat Metab. 2019;1(6):604-614. doi 10.1038/s42255-019-0076-1Hu S., Wang L., Yang D., Li L., Togo J., Wu Y., Liu Q., … Mazidi M., Luo L., Wang S., Douglas A., Speakman J.R. Dietary fat, but not protein or carbohydrate, regulates energy intake and causes adiposity in mice. Cell Metab. 2018;28(3):415-431.e4. doi 10.1016/j.cmet.2018.06.010Hu S., Wang L., Yang D., Li L., Togo J., Wu Y., Liu Q., … Mazidi M., Luo L., Wang S., Douglas A., Speakman J.R. Dietary fat, but not protein or carbohydrate, regulates energy intake and causes adiposity in mice. Cell Metab. 2018;28(3):415-431.e4. doi 10.1016/j.cmet.2018.06.010Hwang L.L., Wang C.H., Li T.L., Chang S.D., Lin L.C., Chen C.P., Chen C.T., Liang K.C., Ho I.K., Yang W.S., Chiou L.C. Sex differences in high‐fat diet‐induced obesity, metabolic alterations and learning, and synaptic plasticity deficits in mice. Obesity. 2010; 18(3):463-469. doi 10.1038/oby.2009.273Hwang L.L., Wang C.H., Li T.L., Chang S.D., Lin L.C., Chen C.P., Chen C.T., Liang K.C., Ho I.K., Yang W.S., Chiou L.C. Sex differences in high‐fat diet‐induced obesity, metabolic alterations and learning, and synaptic plasticity deficits in mice. Obesity. 2010; 18(3):463-469. doi 10.1038/oby.2009.273Keinicke H., Sun G., Mentzel C.M.J., Fredholm M., John L.M., Andersen B., Raun K., Kjaergaard M. FGF21 regulates hepatic metabolic pathways to improve steatosis and inflammation. Endocr Connect. 2020;9(8):755-768. doi 10.1530/EC-20-0152Keinicke H., Sun G., Mentzel C.M.J., Fredholm M., John L.M., Andersen B., Raun K., Kjaergaard M. FGF21 regulates hepatic metabolic pathways to improve steatosis and inflammation. Endocr Connect. 2020;9(8):755-768. doi 10.1530/EC-20-0152Kim H.W., Lee J.E., Cha J.J., Hyun Y.Y., Kim J.E., Lee M.H., Song H.K., Nam D.H., Han J.Y., Han S.Y., Han K.H., Kang Y.S., Cha D.R. Fibroblast growth factor 21 improves insulin resistance and ameliorates renal injury in db/db mice. Endocrinology. 2013; 154(9):3366-3376. doi 10.1210/en.2012-2276Kim H.W., Lee J.E., Cha J.J., Hyun Y.Y., Kim J.E., Lee M.H., Song H.K., Nam D.H., Han J.Y., Han S.Y., Han K.H., Kang Y.S., Cha D.R. Fibroblast growth factor 21 improves insulin resistance and ameliorates renal injury in db/db mice. Endocrinology. 2013; 154(9):3366-3376. doi 10.1210/en.2012-2276Kleiner S., Mepani R.J., Laznik D., Ye L., Jurczak M.J., Jornayvaz F.R., Estall J.L., Chatterjee B.D., Shulman G.I., Spiegelman B.M. Development of insulin resistance in mice lacking PGC-1α in adipose tissues. Proc Natl Acad Sci USA. 2012;109(24):9635-9640. doi 10.1073/pnas.1207287109Kleiner S., Mepani R.J., Laznik D., Ye L., Jurczak M.J., Jornayvaz F.R., Estall J.L., Chatterjee B.D., Shulman G.I., Spiegelman B.M. Development of insulin resistance in mice lacking PGC-1α in adipose tissues. Proc Natl Acad Sci USA. 2012;109(24):9635-9640. doi 10.1073/pnas.1207287109Lau J.K., Zhang X., Yu J. Animal models of non‐alcoholic fatty liver disease: current perspectives and recent advances. J Pathol. 2017; 241(1):36-44. doi 10.1002/path.4829Lau J.K., Zhang X., Yu J. Animal models of non‐alcoholic fatty liver disease: current perspectives and recent advances. J Pathol. 2017; 241(1):36-44. doi 10.1002/path.4829Leow W.Q., Chan A.W.H., Mendoza P.G.L., Lo R., Yap K., Kim H. Nonalcoholic fatty liver disease: the pathologist’s perspective. Clin Mol Hepatol. 2023;29(Suppl):S302-S318. doi 10.3350/cmh.2022.0329Leow W.Q., Chan A.W.H., Mendoza P.G.L., Lo R., Yap K., Kim H. Nonalcoholic fatty liver disease: the pathologist’s perspective. Clin Mol Hepatol. 2023;29(Suppl):S302-S318. doi 10.3350/cmh.2022.0329Li H., Zhang J., Jia W. Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology. Front Med. 2013;7(1): 25-30. doi 10.1007/s11684-013-0244-8Li H., Zhang J., Jia W. Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology. Front Med. 2013;7(1): 25-30. doi 10.1007/s11684-013-0244-8Li J., Wu H., Liu Y., Yang L. High fat diet induced obesity model using four strains of mice: Kunming, C57BL/6, BALB/c and ICR. Exp Anim. 2020;69(3):326-335. doi 10.1538/expanim.19-0148Li J., Wu H., Liu Y., Yang L. High fat diet induced obesity model using four strains of mice: Kunming, C57BL/6, BALB/c and ICR. Exp Anim. 2020;69(3):326-335. doi 10.1538/expanim.19-0148Ma I.L., Stanley T.L. Growth hormone and nonalcoholic fatty liver disease. Immunometabolism 2023;5(3):e00030. doi 10.1097/IN9.0000000000000030Ma I.L., Stanley T.L. Growth hormone and nonalcoholic fatty liver disease. Immunometabolism 2023;5(3):e00030. doi 10.1097/IN9.0000000000000030Makarova E.N., Yakovleva T.V., Balyibina N.Yu., Baranov K.O., Denisova E.I., Dubinina A.D., Feofanova N.A., Bazhan N.M. Pharmacological effects of fibroblast growth factor 21 are sex-specific in mice with the lethal yellow (Ay ) mutation. Vavilov J Genet Breed. 2020;24(2):200-208. doi 10.18699/VJ20.40-oMakarova E.N., Yakovleva T.V., Balyibina N.Yu., Baranov K.O., Denisova E.I., Dubinina A.D., Feofanova N.A., Bazhan N.M. Pharmacological effects of fibroblast growth factor 21 are sex-specific in mice with the lethal yellow (Ay ) mutation. Vavilov J Genet Breed. 2020;24(2):200-208. doi 10.18699/VJ20.40-oMakarova E., Kazantseva A., Dubinina A., Denisova E., Jakovleva T., Balybina N., Bgatova N., Baranov K., Bazhan N. Fibroblast growth factor 21 (FGF21) administration sex-specifically affects blood insulin levels and liver steatosis in obese Ay mice. Cells. 2021a;10(12): 3440. doi 10.3390/cells10123440Makarova E., Kazantseva A., Dubinina A., Denisova E., Jakovleva T., Balybina N., Bgatova N., Baranov K., Bazhan N. Fibroblast growth factor 21 (FGF21) administration sex-specifically affects blood insulin levels and liver steatosis in obese Ay mice. Cells. 2021a;10(12): 3440. doi 10.3390/cells10123440Makarova E., Kazantseva A., Dubinina A., Jakovleva T., Balybina N., Baranov K., Bazhan N. The same metabolic response to FGF21 administration in male and female obese mice is accompanied by sexspecific changes in adipose tissue gene expression. Int J Mol Sci. 2021b;22(19):10561. doi 10.3390/ijms221910561Makarova E., Kazantseva A., Dubinina A., Jakovleva T., Balybina N., Baranov K., Bazhan N. The same metabolic response to FGF21 administration in male and female obese mice is accompanied by sexspecific changes in adipose tissue gene expression. Int J Mol Sci. 2021b;22(19):10561. doi 10.3390/ijms221910561Sanders F.W., Griffin J.L. De novo lipogenesis in the liver in health and disease: more than just a shunting yard for glucose. Biol Rev Camb Philos Soc. 2016;91(2):452-468. doi 10.1111/brv.12178Sanders F.W., Griffin J.L. De novo lipogenesis in the liver in health and disease: more than just a shunting yard for glucose. Biol Rev Camb Philos Soc. 2016;91(2):452-468. doi 10.1111/brv.12178Senthil K.S.P., Shen M., Spicer E.G., Goudjo-Ako A.J., Stumph J.D., Zhang J., Shi H. Distinct metabolic effects following short-term exposure of different high-fat diets in male and female mice. Endocr J. 2014;61(5):457-470. doi 10.1507/endocrj.EJ13-0455Senthil K.S.P., Shen M., Spicer E.G., Goudjo-Ako A.J., Stumph J.D., Zhang J., Shi H. Distinct metabolic effects following short-term exposure of different high-fat diets in male and female mice. Endocr J. 2014;61(5):457-470. doi 10.1507/endocrj.EJ13-0455Speakman J.R. Use of high-fat diets to study rodent obesity as a model of human obesity. Int J Obes. 2019;43(8):1491-1492. doi 10.1038/s41366-019-0363-7Speakman J.R. Use of high-fat diets to study rodent obesity as a model of human obesity. Int J Obes. 2019;43(8):1491-1492. doi 10.1038/s41366-019-0363-7Spruss A., Henkel J., Kanuri G., Blank D., Püschel G.P., Bischoff S.C., Bergheim I. Female mice are more susceptible to nonalcoholic fatty liver disease: Sex-specific regulation of the hepatic AMP-activated protein kinase-plasminogen activator inhibitor 1 cascade, but not the hepatic endotoxin response. Mol Med. 2012;18(1):1346-1355. doi 10.2119/molmed.2012.00223Spruss A., Henkel J., Kanuri G., Blank D., Püschel G.P., Bischoff S.C., Bergheim I. Female mice are more susceptible to nonalcoholic fatty liver disease: Sex-specific regulation of the hepatic AMP-activated protein kinase-plasminogen activator inhibitor 1 cascade, but not the hepatic endotoxin response. Mol Med. 2012;18(1):1346-1355. doi 10.2119/molmed.2012.00223Takaki A., Kawai D., Yamamoto K. Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH). Int J Mol Sci. 2013;14(10):20704-20728. doi 10.3390/ijms141020704Takaki A., Kawai D., Yamamoto K. Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH). Int J Mol Sci. 2013;14(10):20704-20728. doi 10.3390/ijms141020704Xu J., Stanislaus S., Chinookoswong N., Lau Y.Y., Hager T., Patel J., Ge H., … Hecht R., Li Y.-S., Li Y., Lindberg R., Véniant M.M. Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulinresistant mouse models – association with liver and adipose tissue effects. Am J Physiol Endocrinol Metab. 2009;297(5):E1105-E1114. doi 10.1152/ajpendo.00348.2009Xu J., Stanislaus S., Chinookoswong N., Lau Y.Y., Hager T., Patel J., Ge H., … Hecht R., Li Y.-S., Li Y., Lindberg R., Véniant M.M. Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulinresistant mouse models – association with liver and adipose tissue effects. Am J Physiol Endocrinol Metab. 2009;297(5):E1105-E1114. doi 10.1152/ajpendo.00348.2009Yanko R.V., Chaka E.G., Zinchenko A.S., Safonov S.L., Levashov M.L. Features of modeling fatty liver disease in rats of different ages based on a high-calorie diet. Obes Metab. 2021;18(4):387-397. doi 10.14341/omet12789 (in Russia)Yanko R.V., Chaka E.G., Zinchenko A.S., Safonov S.L., Levashov M.L. Features of modeling fatty liver disease in rats of different ages based on a high-calorie diet. Obes Metab. 2021;18(4):387-397. doi 10.14341/omet12789 (in Russia)Ye Q., Jiang Y., Wu D., Cai J., Jiang Z., Zhou Z., Liu L., Ling Q., Wang Q., Zhao G. Atractylodin alleviates nonalcoholic fatty liver disease by regulating Nrf2-mediated ferroptosis. Heliyon. 2023; 9(7):e18321. doi 10.1016/j.heliyon.2023.e18321Ye Q., Jiang Y., Wu D., Cai J., Jiang Z., Zhou Z., Liu L., Ling Q., Wang Q., Zhao G. Atractylodin alleviates nonalcoholic fatty liver disease by regulating Nrf2-mediated ferroptosis. Heliyon. 2023; 9(7):e18321. doi 10.1016/j.heliyon.2023.e18321

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