The dipeptidyl peptidase-4 inhibitor des-fluoro-sitagliptin regulates brown adipose tissue uncoupling protein levels in mice with diet-induced obesity.
The dipeptidyl peptidase-4 inhibitor des-fluoro-sitagliptin regulates brown adipose tissue uncoupling protein levels in mice with diet-induced obesity.
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DOI：
10.1371/journal.pone.0063626
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yoshimatsu H
中科院分区：
文献类型：
--
作者：
Shimasaki T;Masaki T;Mitsutomi K;Ueno D;Gotoh K;Chiba S;Kakuma T;Yoshimatsu H
二肽基肽酶(DPP)-4负责降解几种在倒数第二位或P1位含有丙氨酸或脯氨酸的肽。DPP-4抑制剂（DPP-4is）对2型糖尿病和几种代谢紊乱具有保护作用。在本研究中，我们研究了去氟西格列汀（DFS），一种DDP-4i，对饮食诱导肥胖小鼠体脂肪和过氧化物酶体增殖物激活受体(PPAR)-α， PPAR-γ共激活因子-1 （PGC-1）和解偶联蛋白（UCPs）水平的影响。与对照组相比，DFS治疗剂量依赖性地降低了白色脂肪组织的重量和血清葡萄糖水平，而不影响食物摄入量（P<0.05）。DFS可显著提高褐色脂肪组织（BAT） PPAR-α、PGC-1、UCPs及骨骼肌PPAR-α、UCP3水平（P<0.05）。此外，胰高血糖素样肽1 （GLP-1）拮抗剂exendin对BAT PGC-1和肌肉PPAR-α水平的影响减弱（9-39）。有趣的是，在黑色素皮质素(MC)-4受体缺乏的小鼠中，DFS治疗下丘脑促黑色素皮质素（POMC）水平升高，DFS对PPAR-α、PGC-1和UCP水平的影响减弱。综上所述，高剂量DFS似乎可以通过GLP-1和/或MC-4途径调节饮食性肥胖小鼠的体脂和UCPs。
Dipeptidyl peptidase (DPP)-4 is responsible for the degradation of several peptides that contain an alanine or proline at the penultimate position or position P1. DPP-4 inhibitors (DPP-4is) have protective effects against type-2 diabetes and several metabolic disorders. In the present study, we examined the effects of des-fluoro-sitagliptin (DFS), a DDP-4i, on body adiposity and levels of peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ coactivator-1 (PGC-1), and uncoupling proteins (UCPs) in mice with diet-induced obesity. Treatment with DFS dose-dependently decreased the weight of white adipose tissue and serum levels of glucose, compared with controls, without influencing food intake (P<0.05). Additionally, DFS treatment increased the levels of PPAR-α, PGC-1, and UCPs in brown adipose tissue (BAT), and of PPAR-α and UCP3 in skeletal muscle (P<0.05). Furthermore, the effects on BAT PGC-1 and muscle PPAR-α levels were attenuated by treatment with the glucagon-like peptide 1 (GLP-1) antagonist exendin (9–39). Interestingly, hypothalamic levels of proopiomelanocortin (POMC) were increased by DFS treatment and the effects of DFS on PPAR-α, PGC-1, and UCP levels were attenuated in melanocortin (MC)-4 receptor-deficient mice. In conclusion, high-dose DFS appeared to regulate body adiposity and UCPs in mice with diet-induced obesity, at least partly through a GLP-1 and/or MC-4 pathway.
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影响因子：
7.7
作者：
Lamont, Benjamin J.;Drucker, Daniel J.
通讯作者：
Drucker, Daniel J.
影响因子：
7.7
作者：
Shirakawa J;Fujii H;Ohnuma K;Sato K;Ito Y;Kaji M;Sakamoto E;Koganei M;Sasaki H;Nagashima Y;Amo K;Aoki K;Morimoto C;Takeda E;Terauchi Y
通讯作者：
Terauchi Y
影响因子：
4.8
作者：
Sangle, Ganesh V.;Lauffer, Lina M.;Brubaker, Patricia L.
通讯作者：
Brubaker, Patricia L.
影响因子：
9.8
作者：
Derosa, Giuseppe;Maffioli, Pamela;Cicero, Arrigo F. G.
通讯作者：
Cicero, Arrigo F. G.
影响因子：
2
作者：
Arakawa, Mie;Masaki, Takayuki;Yoshimatsu, Hironobu
通讯作者：
Yoshimatsu, Hironobu