Over-expression of PPARα in obese mice adipose tissue improves insulin sensitivity

被引:23
作者
Takahashi, Haruya [1 ]
Sanada, Kohei [1 ]
Nagai, Hiroyuki [2 ]
Li, Yongjia [1 ]
Aoki, Yumeko [1 ]
Ara, Takeshi [1 ]
Seno, Shigeto [3 ]
Matsuda, Hideo [3 ]
Yu, Rina [4 ]
Kawada, Teruo [1 ,5 ]
Goto, Tsuyoshi [1 ,5 ]
机构
[1] Kyoto Univ, Grad Sch Agr, Div Food Sci & Biotechnol, Lab Mol Funct Food, Uji, Kyoto, Japan
[2] Gifu Prefectural Res Inst Hlth & Environm Sci, Gifu, Japan
[3] Osaka Univ, Grad Sch Informat Sci & Technol, Osaka, Japan
[4] Univ Ulsan, Dept Food Sci & Nutr, Ulsan, South Korea
[5] Kyoto Univ, Res Unit Physiol Chem, Kyoto, Japan
基金
日本学术振兴会; 新加坡国家研究基金会;
关键词
PPAR alpha; Adipose tissue; Insulin sensitivity; PROLIFERATOR-ACTIVATED RECEPTORS; AMINO-ACID CATABOLISM; SKELETAL-MUSCLE; LIPID-METABOLISM; GLUCOSE-UPTAKE; INFLAMMATION; ADIPOCYTES; RESISTANCE; GAMMA; SUPPLEMENTATION;
D O I
10.1016/j.bbrc.2017.09.067
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Peroxisome proliferator-activated receptor a (PPAR alpha) is important in the regulation of lipid metabolism and expressed at high levels in the liver. Although PPAR alpha is also expressed in adipose tissue, little is known about the relationship between its activation and the regulation of glucose metabolism. In this study, we developed adipose tissue specific PPARa over-expression (OE) mice. Metabolomics and insulin tolerance tests showed that OE induces branched-chain amino acid (BCAA) profile and improvement of insulin sensitivity. Furthermore, LC-MS and PCR analyses revealed that OE changes free fatty acid (FFA) profile and reduces obesity-induced inflammation. These findings suggested that PPAR alpha activation in adipose tissue contributes to the improvement of glucose metabolism disorders via the enhancement of BCAA and FFA metabolism. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:108 / 114
页数:7
相关论文
共 52 条
[1]   Dexamethasone induction of hypertension and diabetes is PPAR-α dependent in LDL receptor-null mice [J].
Bernal-Mizrachi, C ;
Weng, S ;
Feng, C ;
Finck, BN ;
Knutsen, RH ;
Leone, TC ;
Coleman, TY ;
Mecham, RP ;
Kelly, DP ;
Semenkovich, CF .
NATURE MEDICINE, 2003, 9 (08) :1069-1075
[2]   PPAR gamma and the molecular control of adipogenesis [J].
Brun, RP ;
Spiegelman, BM .
JOURNAL OF ENDOCRINOLOGY, 1997, 155 (02) :217-218
[3]   Supplemental palmitoleic (C16:1 cis-9) acid reduces lipogenesis and desaturation in bovine adipocyte cultures [J].
Burns, T. A. ;
Duckett, S. K. ;
Pratt, S. L. ;
Jenkins, T. C. .
JOURNAL OF ANIMAL SCIENCE, 2012, 90 (10) :3433-3441
[4]   TNF-α and adipocyte biology [J].
Cawthorn, William P. ;
Sethi, Jaswinder K. .
FEBS LETTERS, 2008, 582 (01) :117-131
[5]   Peroxisome proliferator-activated receptors (PPARs): Nuclear receptors at the crossroads between lipid metabolism and inflammation [J].
Chinetti, G ;
Fruchart, JC ;
Staels, B .
INFLAMMATION RESEARCH, 2000, 49 (10) :497-505
[6]   Overview of clinical perspectives and mechanisms of obesity [J].
Collins, S .
BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY, 2005, 73 (07) :470-471
[7]   Peroxisome proliferator-activated receptors: Nuclear control of metabolism [J].
Desvergne, B ;
Wahli, W .
ENDOCRINE REVIEWS, 1999, 20 (05) :649-688
[8]   Isoleucine, a blood glucose-lowering amino acid, increases glucose uptake in rat skeletal muscle in the absence of increases in AMP-activated protein kinase activity [J].
Doi, M ;
Yamaoka, I ;
Nakayama, M ;
Mochizuki, S ;
Sugahara, K ;
Yoshizawa, F .
JOURNAL OF NUTRITION, 2005, 135 (09) :2103-2108
[9]   Hypoglycemic effect of isoleucine involves increased muscle glucose uptake and whole body glucose oxidation and decreased hepatic gluconeogenesis [J].
Doi, Masako ;
Yamaoka, Ippei ;
Nakayama, Mitsuo ;
Sugahara, Kunio ;
Yoshizawa, Fumiaki .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2007, 292 (06) :E1683-E1693
[10]   The role of PPARs in atherosclerosis [J].
Duval, C ;
Chinetti, G ;
Trottein, F ;
Fruchart, JC ;
Staels, B .
TRENDS IN MOLECULAR MEDICINE, 2002, 8 (09) :422-430