title: Loss of regulator of G protein signaling 5 exacerbates obesity, hepatic steatosis, inflammation and insulin resistance.
abstract: BACKGROUND
  The effect of regulator of G protein signaling 5 (RGS5) on cardiac hypertrophy, atherosclerosis and angiogenesis has been well demonstrated, but the role in the development of obesity and insulin resistance remains completely unknown. We determined the effect of RGS5 deficiency on obesity, hepatic steatosis, inflammation and insulin resistance in mice fed either a normal-chow diet (NC) or a high-fat diet (HF).
  
  
  RESULTS
  Male, 8-week-old RGS5 knockout (KO) and littermate control mice were fed an NC or an HF for 24 weeks and were phenotyped accordingly. RGS5 KO mice exhibited increased obesity, fat mass and ectopic lipid deposition in the liver compared with littermate control mice, regardless of diet. When fed an HF, RGS5 KO mice had a markedly exacerbated metabolic dysfunction and inflammatory state in the blood serum. Meanwhile, macrophage recruitment and inflammation were increased and these increases were associated with the significant activation of JNK, IκBα and NF-κBp65 in the adipose tissue, liver and skeletal muscle of RGS5 KO mice fed an HF relative to control mice. These exacerbated metabolic dysfunction and inflammation are accompanied with decreased systemic insulin sensitivity in the adipose tissue, liver and skeletal muscle of RGS5 KO mice, reflected by weakened Akt/GSK3β phosphorylation.
  
  
  CONCLUSIONS
  Our data suggest that loss of RGS5 exacerbates HF-induced obesity, hepatic steatosis, inflammation and insulin resistance.
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute, Wuhan University, Renmin Hospital, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Xinan
authors.initials: X
authors.lastname: Wang
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Xiao
authors.forename: Kuoju
authors.initials: K
authors.lastname: Chen
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.forename: Difei
authors.initials: D
authors.lastname: Shen
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.forename: Qizhu
authors.initials: Q
authors.lastname: Tang
mesh_terms: D017667:Adipocytes / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D048429:Cell Size; D059305:Diet, High-Fat; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D006946:Hyperinsulinism / Q000235:genetics / Q000503:physiopathology; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology*; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D010084:Oxidation-Reduction / Q000187:drug effects; D020710:RGS Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D020710:RGS Proteins; C498144:Rela protein, mouse; C105346:Rgs5 protein, mouse; D051996:Transcription Factor RelA; D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases