title: Irbesartan ameliorates hyperlipidemia and liver steatosis in type 2 diabetic db/db mice via stimulating PPAR-γ, AMPK/Akt/mTOR signaling and autophagy.
abstract: Irbesartan (Irb), a unique subset of angiotensin II receptor blockers (ARBs) with PPAR-γ activation function, has been reported to play a role in renal dysfunction, glucose metabolism, and abnormal lipid profile in diabetic animal models and humans. However, the underlying mechanisms that improve hyperlipidemia and liver steatosis are unclear. This study investigated the effects of Irb on lipid metabolism and hepatic steatosis using the spontaneous type 2 diabetic db/db mouse model. The results demonstrated body and liver weight, food consumption, lipid content in serum and liver tissue, and liver dysfunction as well as hepatic steatosis were increased in db/db mice compared with db/m mice, whereas the increases were reversed by Irb treatment. Moreover, Irb administration resulted in an increase in LC3BII as well as the LC3BII/I ratio through activating PPAR-γ and p-AMPK and inhibiting p-Akt and p-mTOR, thereby inducing autophagy in the db/db mouse liver. Therefore, our findings suggest that Irb can ameliorate hyperlipidemia and liver steatosis by upregulating the expression of PPAR-γ, activating the AMPK/Akt/mTOR signaling pathway and inducing liver autophagy.
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, PR China; Nephropathy Center of Integrated Traditional Chinese Medicine and Western Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, PR China; Department of Traditional Chinese Medicine, The First People's Hospital of Nanning, Nanning, Guangxi 530022, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Nephropathy Center of Integrated Traditional Chinese Medicine and Western Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, PR China.
authors.forename: Wangqiu
authors.initials: W
authors.lastname: Gong
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, PR China; Nephropathy Center of Integrated Traditional Chinese Medicine and Western Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Laboratory Medicine Center, NanFang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, PR China.
authors.forename: Zibin
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Nephropathy Center of Integrated Traditional Chinese Medicine and Western Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, PR China.
authors.forename: HongYu
authors.initials: H
authors.lastname: Li
authors.affiliation: Nephropathy Center of Integrated Traditional Chinese Medicine and Western Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, PR China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Liu
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, PR China; Nephropathy Center of Integrated Traditional Chinese Medicine and Western Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, PR China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, PR China; Nephropathy Center of Integrated Traditional Chinese Medicine and Western Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, PR China.
authors.forename: Mingqing
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, PR China; Nephropathy Center of Integrated Traditional Chinese Medicine and Western Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, PR China. Electronic address: longhb1966@163.com.
authors.forename: Haibo
authors.initials: H
authors.lastname: Long
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, PR China; Nephropathy Center of Integrated Traditional Chinese Medicine and Western Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, PR China. Electronic address: weilianbo@163.com.
authors.forename: Lianbo
authors.initials: L
authors.lastname: Wei
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001343:Autophagy / Q000187:drug effects; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077405:Irbesartan; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D047495:PPAR gamma / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D047495:PPAR gamma; D013777:Tetrazoles; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000077405:Irbesartan
keywords: AMPK/Akt/mTOR signaling; Autophagy; Hyperlipidemia; Irbesartan; Liver steatosis; PPAR-γ