title: A Novel Function of Hepatic FOG2 in Insulin Sensitivity and Lipid Metabolism Through PPARα.
abstract: Friend of GATA 2 (FOG2) is a transcriptional cofactor involved mostly in cardiac function. The aim of this study was to investigate the role of hepatic FOG2 in insulin sensitivity and lipid accumulation. FOG2 overexpression by adenovirus-expressing FOG2 (Ad-FOG2) significantly attenuates insulin signaling in hepatocytes in vitro. Opposite effects were observed when FOG2 was knocked down through adenovirus-expressing small hairpin RNA for FOG2 (Ad-shFOG2). Furthermore, FOG2 knockdown by Ad-shFOG2 ameliorated insulin resistance in leptin receptor-mutated (db/db) mice, and FOG2 overexpression by Ad-FOG2 attenuated insulin sensitivity in C57BL/6J wild-type (WT) mice. In addition, Ad-FOG2 reduced, whereas Ad-shFOG2 promoted, hepatic triglyceride (TG) accumulation in WT mice under fed or fasted conditions, which was associated with increased or decreased hepatic peroxisome proliferator-activated receptor α (PPARα) expression, respectively. Moreover, the improved insulin sensitivity and increased hepatic TG accumulation by Ad-shFOG2 were largely reversed by adenovirus-expressing PPARα (Ad-PPARα) in WT mice. Finally, we generated FOG2 liver-specific knockout mice and found that they exhibit enhanced insulin sensitivity and elevated hepatic TG accumulation, which were also reversed by Ad-PPARα. Taken together, the results demonstrate a novel function of hepatic FOG2 in insulin sensitivity and lipid metabolism through PPARα.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Yu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Deng
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Feixiang
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Shanghai
authors.initials: S
authors.lastname: Chen
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China ffguo@sibs.ac.cn.
authors.forename: Feifan
authors.initials: F
authors.lastname: Guo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004268:DNA-Binding Proteins; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D047493:PPAR alpha; D054411:Receptors, Leptin; D014157:Transcription Factors; D014280:Triglycerides; C492170:Zfpm2 protein, mouse; D006003:Glycogen; D002784:Cholesterol