RGC32 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice.
Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases and many other chronic diseases. Adipose tissue inflammation is a critical link between obesity and insulin resistance and type 2 diabetes and a contributor to disease susceptibility and progression. The objective of this study was to determine the role of response gene to complement 32 (RGC32) in the development of obesity and insulin resistance. WT and RGC32 knockout (Rgc32(-/-) (Rgcc)) mice were fed normal chow or high-fat diet (HFD) for 12 weeks. Metabolic, biochemical, and histologic analyses were performed. 3T3-L1 preadipocytes were used to study the role of RGC32 in adipocytes in vitro. Rgc32(-/-) mice fed with HFD exhibited a lean phenotype with reduced epididymal fat weight compared with WT controls. Blood biochemical analysis and insulin tolerance test showed that RGC32 deficiency improved HFD-induced dyslipidemia and insulin resistance. Although it had no effect on adipocyte differentiation, RGC32 deficiency ameliorated adipose tissue and systemic inflammation. Moreover, Rgc32(-/-) induced browning of adipose tissues and increased energy expenditure. Our data indicated that RGC32 plays an important role in diet-induced obesity and insulin resistance, and thus it may serve as a potential novel drug target for developing therapeutics to treat obesity and metabolic disorders.
Department of Physiology and PharmacologyUniversity of Georgia, 501 D.W. Brooks Drive, Athens, Georgia 30602, USARenmin HospitalHubei University of Medicine, Shiyan, Hubei 442000, ChinaAntioxidant and Gene Regulation LaboratoryPennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
Xiao-Bing
XB
Cui
Department of Physiology and PharmacologyUniversity of Georgia, 501 D.W. Brooks Drive, Athens, Georgia 30602, USARenmin HospitalHubei University of Medicine, Shiyan, Hubei 442000, ChinaAntioxidant and Gene Regulation LaboratoryPennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
Jun-Na
JN
Luan
Department of Physiology and PharmacologyUniversity of Georgia, 501 D.W. Brooks Drive, Athens, Georgia 30602, USARenmin HospitalHubei University of Medicine, Shiyan, Hubei 442000, ChinaAntioxidant and Gene Regulation LaboratoryPennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
Jianping
J
Ye
Department of Physiology and PharmacologyUniversity of Georgia, 501 D.W. Brooks Drive, Athens, Georgia 30602, USARenmin HospitalHubei University of Medicine, Shiyan, Hubei 442000, ChinaAntioxidant and Gene Regulation LaboratoryPennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA Department of Physiology and PharmacologyUniversity of Georgia, 501 D.W. Brooks Drive, Athens, Georgia 30602, USARenmin HospitalHubei University of Medicine, Shiyan, Hubei 442000, ChinaAntioxidant and Gene Regulation LaboratoryPennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA sc229@uga.edu.
Shi-You
SY
Chen
D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D006706:Homeostasis / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics* / Q000378:metabolism
D009687:Nuclear Proteins; C520017:Rgc-32 protein, mouse
adipose tissue; insulin resistance; obesity; response gene to complement 32