Gastric Bypass Regulates Early Inflammatory Responses in High-Fat Diet-Induced Obese Mice.

Abstract

Obesity and diabetes are characterized by chronic inflammatory responses. Roux-en-Y gastric bypass (RYGB) is increasingly regarded as an effective approach for the improvement of glucose homeostasis. In this study, we examined the effects of RYGB on the regulation of early inflammatory responses in the liver and adipose tissue in high-fat diet (HFD)-induced obese (DIO) mice. RYGB was performed in DIO mice followed by analyses of adiposity, insulin sensitivity, plasma and tissue cytokines and adipokines, tissue NF-κB and JNK/c-Jun activation, and tissue macrophage and T-cell subsets. We found that RYGB resulted in sustained improvement of adiposity and insulin sensitivity. Plasma insulin and leptin levels were increased in untreated DIO mice and reduced in RYGB mice. RYGB maintained plasma adiponectin levels and inhibited monocyte chemoattractant protein-1 and interleukin 6 in white adipose tissue (WAT) and liver. RYGB inhibited NF-κB activation in WAT and muscle, but not in the liver. However, RYGB attenuated the JNK/c-Jun signaling pathway in the liver and WAT at 1wk after surgery, suggesting that RYGB regulates the tissue-specific inflammatory pathway. RYGB reduced M1-like (F4/80+/CD11c+) differentiation and enhanced M2-like population (F4/80+/CD206c+). RYGB also regulated CD4+ and CD8+ T-cell infiltration and increased Treg cells in the liver and WAT at the same time point. Our findings demonstrate that RYGB improves obesity and insulin resistance, which are associated with the regulation of early inflammatory reactions in the liver and WAT.