Bariatric surgery regulates tissue specific inflammation in high fat diet-induced obese mice (50.14)

Abstract Visceral fat deposition induces chronic low grade inflammatory reactions and insulin resistance. However, surgical removal of visceral fat fails to reverse metabolic disease, suggesting that intrahepatic fat, not visceral fat, may be linked with metabolic complications of obesity. Using gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) mouse models, we examined whether the effects of bariatric surgery in the treatment of obesity and insulin resistance were associated with the regulation of inflammation in visceral adipose tissue (VAT) and liver in DIO mice. SG produced weight loss and improved glucose tolerance in the short term, and RYGB, but not SG, resulted in sustained prevention of weight gain and impaired glucose tolerance and decrease in phosphorylation of IRS-1/Ser307 in liver and muscle. RYGB, SG and caloric restriction inhibited NF-kappaB activation in VAT and muscle. RYGB and SG decreased circulating insulin, inhibited proinflammatory cytokine transcription in VAT and reduced CD11b macrophages in liver and in VAT. However, RYGB, but not SG, inhibited CD11c+ cells (-53%) and promoted CD206+ cells (+79%) in liver but not in VAT. RYGB and SG inhibited CD4+/IFNgamma+ subset (-50% and -44%) in DIO VAT, and only RYGB enhanced CD4+/IL-10+ subset (+100%) in DIO liver. We conclude that the improvements in insulin resistance associated with RYGB and SG appear to be modulated by the inhibition of inflammation in a tissue specific manner.