期刊
DIABETES
卷 60, 期 4, 页码 1246-1257出版社
AMER DIABETES ASSOC
DOI: 10.2337/db10-1338
关键词
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资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [19390251, 21390282]
- Japan Medical Association
- Japan Diabetes Foundation
- Suzuken Memorial Foundation
- Naito Foundation
- Uehara Memorial Foundation
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [22650223, 09J03269, 21390282, 23591315, 21300277, 19390251, 22590437, 22390200] Funding Source: KAKEN
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
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