Diet-Induced Adipose Tissue Inflammation and Liver Steatosis Are Prevented by DPP-4 Inhibition in Diabetic Mice

作者：Shirakawa Jun; Fujii Hideki; Ohnuma Kei; Sato Koichiro; Ito Yuzuru; Kaji Mitsuyo; Sakamoto Eri; Koganei Megumi; Sasaki Hajime; Nagashima Yoji; Amo Kikuko; Aoki Kazutaka; Morimoto Chikao; Takeda Eiji; Terauchi Yasuo^*

来源：Diabetes, 2011, 60(4): 1246-1257.

DOI：10.2337/db10-1338

OBJECTIVE-Diet composition alters the metabolic states of adipocytes and hepatocytes in diabetes. The effects of dipeptidyl peptidase-4 (DPP-4) inhibition on adipose tissue inflammation and fatty liver have been obscure. We investigated the extra-pancreatic effects of DPP-4 inhibition on visceral fat and the liver.
RESEARCH DESIGN AND METHODS-We investigated diet-induced metabolic changes in beta-cell-specific glucokinase haplo-insufficient (Gck(+/-)) diabetic mice. We challenged animals with a diet containing a combination of sucrose and oleic acid (SO) or sucrose and linoleic acid (SL). Next, we assessed the effects of a DPP-4 inhibitor, des-fluoro-sitagliptin, on adipose tissue inflammation and hepatic steatosis.
RESULTS-The epididymal fat weight and serum leptin level were significantly higher in Gck(+/-) mice fed SL than in mice fed SO, although no significant differences in body weight or adipocyte size were noted. Compared with SO, SL increased the numbers of CD11c(+) M1 macrophages and CDS(+) T-cells in visceral adipose tissue and the expression of E-selectin, P-selectin, and plasminogen activator inhibitor-1 (PAI-1). DPP-4 inhibition significantly prevented adipose tissue infiltration by CDS+ T-cells and M1 macrophages and decreased the expression of PAI-1. The production of cytokines by activated T-cells was not affected by DPP-4 inhibition. Furthermore, DPP-4 inhibition prevented fatty liver in both wild-type and Gck(+/-) mice. DPP-4 inhibition also decreased the expressions of sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase-1, and fatty acid synthase, and increased the expression of peroxisome proliferator-activated receptor-a in the liver.
CONCLUSIONS-Our findings indicated that DPP-4 inhibition has extrapancreatic protective effects against diet-induced adipose tissue inflammation and hepatic steatosis. Diabetes 60:1246-1257, 2011

• 出版日期2011-4
• 单位河北医科大学