title: HNF-4α regulated miR-122 contributes to development of gluconeogenesis and lipid metabolism disorders in Type 2 diabetic mice and in palmitate-treated HepG2 cells.
abstract: Hepatocyte Nuclear Factor-4α (HNF-4α) is a key nuclear receptor protein required for liver development. miR-122 is a predominant microRNA expressed in liver and is involved in the regulation of cholesterol and fatty acid metabolism. HNF-4α is know to regulate expression of miR-122 in liver. We examined how HNF-4α regulated gluconeogenesis and lipid metabolism through miR-122 in vivo and in vitro. Expression of miR-122, HNF-4α, phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), sterol response elementary binding protein-1 (SREBP-1), fatty acid synthase-1 (FAS-1), carnitine palmitoyltransferase-1 (CPT-1) and acetyl Coenzyme A carboxylase alpha (ACCα) were determined in livers of Type 2 diabetic mice and in insulin resistant palmitate-treated HepG2 cells. CPT-1 and phosphorylated ACCα expression were significantly decreased in livers of Type 2 diabetic mice and in palmitate-treated HepG2 cells compared to controls. In contrast, expression of miR-122, HNF-4α, PEPCK, G6Pase, SREBP-1, FAS-1 and ACCα were significantly elevated in liver of Type 2 diabetic mice and in palmitate-treated HepG2 cells compared to controls. Expression of HNF-4α increased whereas siRNA knockdown of HNF-4α decreased miR-122 levels in HepG2 cells compared to controls. In addition, expression of HNF-4α in HepG2 cells increased PEPCK, G6Pase, SREBP-1, FAS-1, ACCα mRNA and protein expression and decreased CPT-1 and p-ACCα mRNA and protein expression compared to controls. Addition of miR-122 inhibitors attenuated the HNF-4α mediated effect on expression of these gluconeogenic and lipid metabolism proteins. The results indicate that HNF-4α regulated miR-122 contributes to development of the gluconeogenic and lipid metabolism alterations observed in Type 2 diabetic mice and in palmitate-treated HepG2 cells.
authors: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, Jilin, China.
authors: Shengnan
authors: S
authors: Wei
authors: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, Jilin, China.
authors: Ming
authors: M
authors: Zhang
authors: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, Jilin, China.
authors: Yang
authors: Y
authors: Yu
authors: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, Jilin, China.
authors: Huan
authors: H
authors: Xue
authors: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, Jilin, China.
authors: Xiaoxin
authors: X
authors: Lan
authors: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, Jilin, China.
authors: Shuping
authors: S
authors: Liu
authors: Department of Pharmacology & Therapeutics, University of Manitoba, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada. Electronic address: ghatch@chrim.ca.
authors: Grant
authors: G
authors: Hatch
authors: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, Jilin, China. Electronic address: chen_lab@163.com.
authors: Li
authors: L
authors: Chen
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005943:Gluconeogenesis / Q000187:drug effects / Q000235:genetics; D056945:Hep G2 Cells; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010168:Palmitates / Q000494:pharmacology*
chemical_list: D051557:Hepatocyte Nuclear Factor 4; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; C544354:Mirn122 microRNA, mouse; D010168:Palmitates
keywords: Gluconeogenesis; HNF-4α; Lipid metabolism; MiR122; Type 2 diabetes