Ablation of PPP1R3G reduces glycogen deposition and mitigates high-fat diet induced obesity.
Glycogen and triglyceride are two major forms of energy storage in the body and provide the fuel during different phases of food deprivation. However, how glycogen metabolism is linked to fat deposition in adipose tissue has not been clearly characterized. We generated a mouse model with whole-body deletion of PPP1R3G, a glycogen-targeting subunit of protein phosphatase-1 required for glycogen synthesis. Upon feeding with high-fat diet, the body weight and fat composition are significantly reduced in the PPP1R3G-/-mice compared to the wild type controls. The metabolic rate of the mice as measured by O2consumption and CO2production is accelerated by PPP1R3G deletion. The high-fat diet-induced liver steatosis is also slightly relieved by PPP1R3G deletion. The glycogen level in adipose tissue is reduced by PPP1R3G deletion. In 3T3L1 cells, overexpression of PPP1R3G leads to increases of both glycogen and triglyceride levels. In conclusion, our study indicates that glycogen is actively involved in fat accumulation in adipose tissue and obesity development upon high-fat diet. Our study also suggests that PPP1R3G is an important player that links glycogen metabolism to lipid metabolism in vivo.
CAS Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Yongxian
Y
Zhang
CAS Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Jin
J
Gu
CAS Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Lin
L
Wang
CAS Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Zilong
Z
Zhao
CAS Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Yi
Y
Pan
CAS Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. Electronic address: ychen3@sibs.ac.cn.
Yan
Y
Chen
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001481:Basal Metabolism; D001786:Blood Glucose / Q000378:metabolism; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D006003:Glycogen / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D019518:Postprandial Period; D054645:Protein Phosphatase 1 / Q000172:deficiency* / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D001786:Blood Glucose; D014280:Triglycerides; D006003:Glycogen; C000591005:PPP1R3G protein, mouse; D054645:Protein Phosphatase 1
Adipocytes; Glycogen; Hepatic steatosis; Insulin resistance; Obesity