{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:18:22Z","timestamp":1791667102063,"version":"4.3.4"},"reference-count":63,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["322711"],"award-info":[{"award-number":["322711"]}]},{"name":"National Natural Science Foundation of China","award":["23AZD092"],"award-info":[{"award-number":["23AZD092"]}]},{"name":"National Natural Science Foundation of China","award":["32571316"],"award-info":[{"award-number":["32571316"]}]},{"name":"Key Program of National Social Science Fund of China","award":["322711"],"award-info":[{"award-number":["322711"]}]},{"name":"Key Program of National Social Science Fund of China","award":["23AZD092"],"award-info":[{"award-number":["23AZD092"]}]},{"name":"Key Program of National Social Science Fund of China","award":["32571316"],"award-info":[{"award-number":["32571316"]}]},{"name":"National Natural Science Foundation of China","award":["322711"],"award-info":[{"award-number":["322711"]}]},{"name":"National Natural Science Foundation of China","award":["23AZD092"],"award-info":[{"award-number":["23AZD092"]}]},{"name":"National Natural Science Foundation of China","award":["32571316"],"award-info":[{"award-number":["32571316"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: This study aimed to investigate the effects of long-term aerobic exercise on high-fat diet (HFD)-induced hepatic steatosis and its underlying enterohepatic communication mechanisms. Methods: C57BL\/6J mice were divided into four groups: normal-diet with sedentary (ND-SED), normal-diet with exercise (ND-EXE), HFD with sedentary (HFD-SED), and HFD with exercise (HFD-EXE). After 16 weeks of HFD feeding, ND-EXE and HFD-EXE groups underwent an 8-week aerobic exercise intervention. Hepatic lipid accumulation was assessed via histology and triglyceride (TG) quantification. Liver function and glucose tolerance were evaluated. Gut microbiota composition (16S rRNA sequencing), hepatic bile acid profiles (LC-MS metabolomics), and gene expression were analyzed. Results: HFD induced hepatic steatosis, glucose intolerance, and liver injury in mice, all of which were ameliorated by exercise. Compared to HFD-SED mice, which exhibited impaired gut microbiota diversity, exercise restored key genera such as Faecalibaculum, and Turicibacter. Functional analysis revealed that exercise modulated microbiota shifts in lipid metabolism and secondary bile acid biosynthesis. HFD-EXE mice displayed altered hepatic bile acid composition, characterized by increased tauroursodeoxycholic acid (TUDCA) and reduced taurohyodeoxycholic acid (THDCA). Notably, TUDCA levels correlated with Turicibacter abundance, while deoxycholic acid (DCA) was associated with Faecalibaculum, independent of precursor availability. Exercise also suppressed hepatic endoplasmic reticulum (ER) stress and downregulated lipogenic genes via the inositol-requiring enzyme 1 alpha (IRE1\u03b1)- spliced X-box binding protein 1 (Xbp1s) pathway, while concurrently activating farnesoid X receptor (FXR) signaling to enhance fatty acid oxidation through the FXR-short heterodimer partner (SHP) related to hepatic secondary bile acid abundance change. Conclusions: The beneficial effect of long-term aerobic exercise on high-fat diet-induced hepatic steatosis in mice is potentially mediated through structural changes in the gut microbiota, which influence the abundance of hepatic secondary bile acids (TUDCA, DCA) and subsequently regulate the expression of genes involved in lipid metabolism.<\/jats:p>","DOI":"10.3390\/nu17182962","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T16:27:33Z","timestamp":1757953653000},"page":"2962","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Exercise-Induced Changes in Enterohepatic Communication Are Linked to Liver Steatosis Resolution"],"prefix":"10.3390","volume":"17","author":[{"given":"Yong","family":"Zou","sequence":"first","affiliation":[{"name":"Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China"},{"name":"College of Physical Education and Health, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Physical Education, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China"},{"name":"College of Physical Education and Health, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Guo","sequence":"additional","affiliation":[{"name":"Arc Institute, Palo Alto, CA 94304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weina","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China"},{"name":"College of Physical Education and Health, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3764-6396","authenticated-orcid":false,"given":"Zhengtang","family":"Qi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China"},{"name":"College of Physical Education and Health, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/S0140-6736(20)32511-3","article-title":"Non-alcoholic fatty liver disease","volume":"397","author":"Powell","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.3350\/cmh.2022.0365","article-title":"Global incidence and prevalence of nonalcoholic fatty liver disease","volume":"29","author":"Teng","year":"2023","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1136\/gutjnl-2020-322786","article-title":"Mortality in biopsy-confirmed nonalcoholic fatty liver disease: Results from a nationwide cohort","volume":"70","author":"Simon","year":"2021","journal-title":"Gut"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1111\/apt.15673","article-title":"Modelling NAFLD disease burden in four Asian regions-2019\u20132030","volume":"51","author":"Estes","year":"2020","journal-title":"Aliment. Pharm. Ther."},{"key":"ref_5","unstructured":"European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), and European Association for the Study of Obesity (EASO) (2024). EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J. Hepatol., 81, 492\u2013542."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/s41575-020-0269-9","article-title":"Gut microbiota and human NAFLD: Disentangling microbial signatures from metabolic disorders","volume":"17","author":"Vigliotti","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41467-020-20422-7","article-title":"Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma","volume":"12","author":"Behary","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Nychas, E., Marfil-S\u00e1nchez, A., Chen, X., Mirhakkak, M., Li, H., Jia, W., Xu, A., Nielsen, H.B., Nieuwdorp, M., and Loomba, R. (2025). Discovery of robust and highly specific microbiome signatures of non-alcoholic fatty liver disease. Microbiome, 13.","DOI":"10.1186\/s40168-024-01990-y"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/s41467-023-35861-1","article-title":"Western diet contributes to the pathogenesis of non-alcoholic steatohepatitis in male mice via remodeling gut microbiota and increasing production of 2-oleoylglycerol","volume":"14","author":"Yang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1016\/j.cmet.2023.08.002","article-title":"Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations","volume":"35","author":"Ni","year":"2023","journal-title":"Cell Metab."},{"key":"ref_11","first-page":"308","article-title":"The human gut microbiota: Metabolism and perspective in obesity","volume":"9","author":"Gomes","year":"2018","journal-title":"Gut Microbes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.tim.2017.11.002","article-title":"Human Gut Microbiome: Function Matters","volume":"26","author":"Wilmes","year":"2018","journal-title":"Trends Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41575-018-0061-2","article-title":"You are what you eat: Diet, health and the gut microbiota","volume":"16","author":"Zmora","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1038\/s42255-024-01108-6","article-title":"Feeding gut microbes to nourish the brain: Unravelling the diet-microbiota-gut-brain axis","volume":"6","author":"Schneider","year":"2024","journal-title":"Nat. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1093\/cvr\/cvad023","article-title":"Heart-gut microbiota communication determines the severity of cardiac injury after myocardial ischaemia\/reperfusion","volume":"119","author":"Zhao","year":"2023","journal-title":"Cardiovasc. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1038\/s41467-022-29968-0","article-title":"A randomized controlled trial for response of microbiome network to exercise and diet intervention in patients with nonalcoholic fatty liver disease","volume":"13","author":"Cheng","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Phelps, C.M., Willis, N.B., Duan, T., Lee, A.H., Zhang, Y., Rodriguez, J.D.M., Pandey, S.P., Laughlin, C.R., Rosen, A.B.I., and McPherson, A.C. (2025). Exercise-induced microbiota metabolite enhances CD8 T cell antitumor immunity promoting immunotherapy efficacy. Cell, Online ahead of print.","DOI":"10.1016\/j.cell.2025.06.018"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1038\/s12276-020-0459-0","article-title":"Exercise training modulates the gut microbiota profile and impairs inflammatory signaling pathways in obese children","volume":"52","author":"Quiroga","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.metabol.2015.01.015","article-title":"AMPK binds to Sestrins and mediates the effect of exercise to increase insulin-sensitivity through autophagy","volume":"64","author":"Liu","year":"2015","journal-title":"Metabolism"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yang, Y., Li, X., Liu, Z., Ruan, X., Wang, H., Zhang, Q., Cao, L., Song, L., Chen, Y., and Sun, Y. (2022). Moderate treadmill exercise alleviates nafld by regulating the biogenesis and autophagy of lipid droplet. Nutrients, 14.","DOI":"10.3390\/nu14224910"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2192155","DOI":"10.1080\/19490976.2023.2192155","article-title":"Glycoursodeoxycholic acid regulates bile acids level and alters gut microbiota and glycolipid metabolism to attenuate diabetes","volume":"15","author":"Chen","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s41574-022-00794-0","article-title":"The gut microbiota in obesity and weight management: Microbes as friends or foe?","volume":"19","author":"Cani","year":"2023","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41579-022-00805-x","article-title":"Bile acids and the gut microbiota: Metabolic interactions and impacts on disease","volume":"21","author":"Collins","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1053\/j.gastro.2025.01.224","article-title":"Exercise, the Gut Microbiome and Gastrointestinal Diseases: Therapeutic Impact and Molecular Mechanisms","volume":"169","author":"Hawley","year":"2025","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jshs.2016.05.001","article-title":"Endurance exercise and gut microbiota: A review","volume":"6","author":"Mach","year":"2017","journal-title":"J. Sport Health Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e969","DOI":"10.1016\/S2666-5247(22)00203-8","article-title":"The gut mycobiome in health, disease, and clinical applications in association with the gut bacterial microbiome assembly","volume":"3","author":"Zhang","year":"2022","journal-title":"Lancet Microbe"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1136\/gutjnl-2013-306541","article-title":"Exercise and associated dietary extremes impact on gut microbial diversity","volume":"63","author":"Clarke","year":"2014","journal-title":"Gut"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1249\/MSS.0000000000001495","article-title":"Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans","volume":"50","author":"Allen","year":"2018","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nature12506","article-title":"Richness of human gut microbiome correlates with metabolic markers","volume":"500","author":"Nielsen","year":"2013","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1080\/19490976.2018.1562268","article-title":"Exercise influence on the microbiome-gut-brain axis","volume":"10","author":"Dalton","year":"2019","journal-title":"Gut Microbes"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Liu, W., Huang, Z., Zhang, Y., Zhang, S., Cui, Z., Liu, W., Li, L., Xia, J., Zou, Y., and Qi, Z. (2023). ASMT determines gut microbiota and increases neurobehavioral adaptability to exercise in female mice. Commun. Biol., 6.","DOI":"10.1038\/s42003-023-05520-8"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"dmm039206","DOI":"10.1242\/dmm.039206","article-title":"Beneficial effects of exercise on gut microbiota functionality and barrier integrity, and gut-liver crosstalk in an in vivo model of early obesity and non-alcoholic fatty liver disease","volume":"12","author":"Porras","year":"2019","journal-title":"Dis. Model Mech."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/nature05414","article-title":"An obesity-associated gut microbiome with increased capacity for energy harvest","volume":"444","author":"Turnbaugh","year":"2006","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1249\/MSS.0000000000002112","article-title":"Exercise Training Modulates Gut Microbiota Profile and Improves Endotoxemia","volume":"52","author":"Motiani","year":"2020","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/1750-1326-9-36","article-title":"Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition","volume":"9","author":"Kang","year":"2014","journal-title":"Mol. Neurodegener."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Min, L., Ablitip, A., Wang, R., Luciana, T., Wei, M., and Ma, X. (2024). Effects of Exercise on Gut Microbiota of Adults: A Systematic Review and Meta-Analysis. Nutrients, 16.","DOI":"10.3390\/nu16071070"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1016\/j.jhep.2023.07.005","article-title":"Bifidobacterium pseudolongum-generated acetate suppresses non-alcoholic fatty liver disease-associated hepatocellular carcinoma","volume":"79","author":"Song","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"109025","DOI":"10.1016\/j.envint.2024.109025","article-title":"Long-term arsenic exposure decreases mice body weight and liver lipid droplets","volume":"192","author":"Lai","year":"2024","journal-title":"Environ. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41538-024-00334-2","article-title":"Ampelopsis grossedentata tea alleviating liver fibrosis in BDL-induced mice via gut microbiota and metabolite modulation","volume":"8","author":"Xi","year":"2024","journal-title":"npj Sci. Food"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7312","DOI":"10.1021\/acs.jafc.2c08637","article-title":"Nobiletin Ameliorates Nonalcoholic Fatty Liver Disease by Regulating Gut Microbiota and Myristoleic Acid Metabolism","volume":"71","author":"Li","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_41","first-page":"155111","article-title":"Xie Zhuo Tiao Zhi formula modulates intestinal microbiota and liver purine metabolism to suppress hepatic steatosis and pyroptosis in NAFLD therapy","volume":"121","author":"Qiu","year":"2023","journal-title":"Phytomedicine Int. J. Phytother. Phytopharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1111\/1751-7915.14293","article-title":"Akkermansia muciniphila alleviates high-fat-diet-related metabolic-associated fatty liver disease by modulating gut microbiota and bile acids","volume":"16","author":"Wu","year":"2023","journal-title":"Microb. Biotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Xu, H., Fang, F., Wu, K., Song, J., Li, Y., Lu, X., Liu, J., Zhou, L., Yu, W., and Yu, F. (2023). Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia. Microbiome, 11.","DOI":"10.1186\/s40168-023-01709-5"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1152\/physrev.00049.2019","article-title":"Molecular Physiology of Bile Acid Signaling in Health, Disease, and Aging","volume":"101","author":"Perino","year":"2021","journal-title":"Physiol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1152\/japplphysiol.00777.2009","article-title":"Voluntary wheel running exercise and dietary lactose concomitantly reduce proportion of secondary bile acids in rat feces","volume":"109","author":"Hagio","year":"2010","journal-title":"J. Appl. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"zqaf019","DOI":"10.1093\/function\/zqaf019","article-title":"Aerobic Capacity and Exercise Mediate Protection Against Hepatic Steatosis via Enhanced Bile Acid Metabolism","volume":"6","author":"Kugler","year":"2025","journal-title":"Function"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.atherosclerosis.2011.06.040","article-title":"Voluntary wheel running increases bile acid as well as cholesterol excretion and decreases atherosclerosis in hypercholesterolemic mice","volume":"218","author":"Meissner","year":"2011","journal-title":"Atherosclerosis"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100387","DOI":"10.1016\/j.jhepr.2021.100387","article-title":"Bile acids contribute to the development of non-alcoholic steatohepatitis in mice","volume":"4","author":"Gillard","year":"2022","journal-title":"JHEP Rep. Innov. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1152\/japplphysiol.01292.2007","article-title":"Endurance exercise training reduces gallstone development in mice","volume":"104","author":"Wilund","year":"2008","journal-title":"J. Appl. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/bph.14095","article-title":"Tauroursodeoxycholic acid inhibits intestinal inflammation and barrier disruption in mice with non-alcoholic fatty liver disease","volume":"175","author":"Wang","year":"2018","journal-title":"Brit. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1249\/MSS.0000000000003384","article-title":"Exercise Training Independent of Intensity Lowers Plasma Bile Acids in Prediabetes","volume":"56","author":"Malin","year":"2024","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1038\/s41564-019-0540-4","article-title":"Intestinal serotonin and fluoxetine exposure modulate bacterial colonization in the gut","volume":"4","author":"Fung","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.1038\/s41467-023-39403-7","article-title":"Gut microbiota Turicibacter strains differentially modify bile acids and host lipids","volume":"14","author":"Lynch","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Kemis, J.H., Linke, V., Barrett, K.L., Boehm, F.J., Traeger, L.L., Keller, M.P., Rabaglia, M.E., Schueler, K.L., Stapleton, D.S., and Gatti, D.M. (2019). Genetic determinants of gut microbiota composition and bile acid profiles in mice. PLoS Genet., 15.","DOI":"10.1101\/571075"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Mu, H., Zhou, Q., Yang, R., Zeng, J., Li, X., Zhang, R., Tang, W., Li, H., Wang, S., and Shen, T. (2020). Naringin Attenuates High Fat Diet Induced Non-alcoholic Fatty Liver Disease and Gut Bacterial Dysbiosis in Mice. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.585066"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.jhep.2018.06.008","article-title":"Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease","volume":"69","author":"Lebeaupin","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7715","DOI":"10.1038\/s41467-022-35310-5","article-title":"Upper gut heat shock proteins HSP70 and GRP78 promote insulin resistance, hyperglycemia, and non-alcoholic steatohepatitis","volume":"13","author":"Angelini","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"111707","DOI":"10.1016\/j.celrep.2022.111707","article-title":"circPRKAA1 activates a Ku80\/Ku70\/SREBP-1 axis driving de novo fatty acid synthesis in cancer cells","volume":"41","author":"Li","year":"2022","journal-title":"Cell Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.4103\/0366-6999.241799","article-title":"Role of X-box binding protein-1 in fructose-induced de novo lipogenesis in HepG2 cells","volume":"131","author":"Yu","year":"2018","journal-title":"Chin. Med. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1016\/j.cmet.2021.06.012","article-title":"FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption","volume":"33","author":"Clifford","year":"2021","journal-title":"Cell Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1016\/j.cmet.2023.07.011","article-title":"Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis","volume":"35","author":"Kuang","year":"2023","journal-title":"Cell Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.molmet.2015.09.005","article-title":"Bioenergetic cues shift FXR splicing towards FXR\u03b12 to modulate hepatic lipolysis and fatty acid metabolism","volume":"4","author":"Correia","year":"2015","journal-title":"Mol. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"155241","DOI":"10.1016\/j.metabol.2022.155241","article-title":"Higd1a facilitates exercise-mediated alleviation of fatty liver in diet-induced obese mice","volume":"134","author":"Zhu","year":"2022","journal-title":"Metab. Clin. Exp."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/18\/2962\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:46:06Z","timestamp":1760035566000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/18\/2962"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,15]]},"references-count":63,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["nu17182962"],"URL":"https:\/\/doi.org\/10.3390\/nu17182962","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,15]]}}}