title: Regulation of glucose homeostasis and lipid metabolism by PPP1R3G-mediated hepatic glycogenesis.
abstract: Liver glycogen metabolism plays an important role in glucose homeostasis. Glycogen synthesis is mainly regulated by glycogen synthase that is dephosphorylated and activated by protein phosphatase 1 (PP1) in combination with glycogen-targeting subunits or G subunits. There are seven G subunits (PPP1R3A to G) that control glycogenesis in different organs. PPP1R3G is a recently discovered G subunit whose expression is changed along the fasting-feeding cycle and is proposed to play a role in postprandial glucose homeostasis. In this study, we analyzed the physiological function of PPP1R3G using a mouse model with liver-specific overexpression of PPP1R3G. PPP1R3G overexpression increases hepatic glycogen accumulation, stimulates glycogen synthase activity, elevates fasting blood glucose level, and accelerates postprandial blood glucose clearance. In addition, the transgenic mice have a reduced fat composition, together with decreased hepatic triglyceride level. Fasting-induced hepatic steatosis is relieved by PPP1R3G overexpression. In addition, PPP1R3G overexpression is able to elevate glycogenesis in primary hepatocytes. The glycogen-binding domain is indispensable for the physiological activities of PPP1R3G on glucose metabolism and triglyceride accumulation in the liver. Cumulatively, these data indicate that PPP1R3G plays a critical role in postprandial glucose homeostasis and liver triglyceride metabolism via its regulation on hepatic glycogenesis.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yongxian
authors.initials: Y
authors.lastname: Zhang
authors.forename: Daqian
authors.initials: D
authors.lastname: Xu
authors.forename: Heng
authors.initials: H
authors.lastname: Huang
authors.forename: Susie
authors.initials: S
authors.lastname: Chen
authors.forename: Lingdi
authors.initials: L
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Zhu
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Jiang
authors.forename: Xiangbo
authors.initials: X
authors.lastname: Ruan
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Luo
authors.forename: Peijuan
authors.initials: P
authors.lastname: Cao
authors.forename: Weizhong
authors.initials: W
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D001665:Binding Sites; D001786:Blood Glucose; D002478:Cells, Cultured; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006706:Homeostasis; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000096:biosynthesis*; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D061251:Primary Cell Culture; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D008112:Liver Glycogen; D014280:Triglycerides; C000591005:PPP1R3G protein, mouse; D054645:Protein Phosphatase 1; D005947:Glucose