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- Title
Diet-Induced Adipose Tissue Inflammation and Liver Steatosis Are Prevented by DPP-4 Inhibition in Diabetic Mice.
- Authors
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
- Abstract
OBJECTIVE--Diet composition alters the metabolic states of adipocytes and hepatocytes in diabetes. The effects of dipeptidyl peptidase4 (DPP-4) inhibition on adipose tissue inflammation and fatty liver have been obscure. We investigated the extrapancreatic effects of DPP-4 inhibition on visceral fat and the liver. RESEARCH DESIGN AND METHODS--We investigated diet-induced metabolic changes in β-cell-specific glucokinase haploinsufficient (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 CD8+ 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 CD8+ 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-α in the liver. CONCLUSIONS--Our findings indicated that DPP-4 inhibition has extrapancreatic protective effects against diet-induced adipose tissue inflammation and hepatic steatosis.
- Subjects
DIET; FAT cells; LIVER cells; DIABETES; CD26 antigen; SUCROSE
- Publication
Diabetes, 2011, Vol 60, Issue 4, p1246
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db10-1338