title: Fenofibrate treatment attenuated chronic endoplasmic reticulum stress in the liver of nonalcoholic fatty liver disease mice.
abstract: Fenofibrate is widely used in clinical practice, but its influence on chronic endoplasmic reticulum (ER) stress induced by feeding a high-calorie and high-cholesterol diet (HCD) has still not been studied. We thus investigated its effects on the liver of the nonalcoholic fatty liver disease (NAFLD) mouse model. Male C57BL/6 mice fed an HCD for 3 months were treated with fenofibrate (HCD + FF, 40 mg/kg, once daily) via gavage for 4 weeks. Insulin sensitivity, serum lipid and inflammatory cytokines were measured. Liver tissues were procured for histological examination as well as analysis of hepatic triglyceride levels, distribution of inflammatory cytokines and genes involved in ER stress. Our results showed that chronic feeding of an HCD successfully induced an NAFLD model accompanied by inflammatory activation, apoptosis and severe ER stress in the liver. Fenofibrate administration significantly improved symptoms of NAFLD and decreased apoptosis, expression of inflammatory cytokines and genes involved in ER stress, such as inositol-requiring enzyme 1α (IRE1α), X-box binding protein 1 (XBP1) and JNK phosphorylation. Thus, our study suggests that fenofibrate protected against inflammatory injury and apoptosis, maybe alleviating ER stress through the IRE1α-XBP1-JNK pathway in the liver of NAFLD mice.
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Lu
authors.forename: Xinru
authors.initials: X
authors.lastname: Shen
authors.forename: Yingying
authors.initials: Y
authors.lastname: Bao
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cheng
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Bao
authors.initials: B
authors.lastname: Li
authors.forename: Qiu
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000188:drug therapy; D047493:PPAR alpha / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D001786:Blood Glucose; C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D051742:Transcription Factor CHOP; D002784:Cholesterol; C510185:Ern1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D048670:MAP Kinase Kinase 4; D004722:Endoribonucleases; D011345:Fenofibrate