Thioesterase Superfamily Member 2 (Them2) and Phosphatidylcholine Transfer Protein (PC-TP) Interact To Promote Fatty Acid Oxidation and Control Glucose Utilization

被引：29

作者：

Kawano, Yuki ^{[1
]}

Ersoy, Baran A. ^{[1
]}

Li, Yingxia ^{[1
]}

Nishiumi, Shin ^{[2
]}

Yoshida, Masaru ^{[2
,3
,4
]}

Cohen, David E. ^{[1
]}

机构：

[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Gastroenterol, Boston, MA 02115 USA

[2] Kobe Univ, Grad Sch Med, Div Gastroenterol, Dept Internal Med, Kobe, Hyogo 657, Japan

[3] Kobe Univ, Grad Sch Med, Div Metabol Res, Dept Internal Med Related, Kobe, Hyogo 657, Japan

[4] Kobe Univ, Grad Sch Med, Integrated Ctr Mass Spectrometry, Kobe, Hyogo 657, Japan

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2014年 / 34卷 / 13期

基金：

美国国家卫生研究院;

关键词：

ACTIVATED RECEPTOR-ALPHA; PPAR-ALPHA; HEPATIC GLUCONEOGENESIS; ADAPTIVE THERMOGENESIS; METABOLIC-RESPONSE; MICE; TRANSCRIPTION; PGC-1-ALPHA; KINASE; LIVER;

D O I：

10.1128/MCB.01601-13

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：

Thioesterase superfamily member 2 (Them2) is a mitochondrion-associated long-chain fatty acyl coenzyme A (CoA) thioesterase that is highly expressed in the liver and oxidative tissues. Them2 activity in vitro is increased when it interacts with phosphatidylcholine transfer protein (PC-TP), a cytosolic lipid binding protein. Them2(-/-) and Pctp(-/-) mice exhibit enhanced hepatic insulin sensitivity and increased adaptive thermogenesis, and Them2(-/-) mice are also resistant to diet-induced hepatic steatosis. Although we showed previously that a Them2-PC-TP complex suppresses insulin signaling, the enzymatic activity of Them2 suggests additional direct involvement in regulating hepatic nutrient homeostasis. Here we used cultured primary hepatocytes to elucidate biochemical and cellular mechanisms by which Them2 and PC-TP regulate lipid and glucose metabolism. Under conditions simulating fasting, Them2(-/-) and Pctp(-/-) hepatocytes each exhibited decreased rates of fatty acid oxidation and gluconeogenesis. In results indicative of Them2-dependent regulation by PC-TP, chemical inhibition of PC-TP failed to reproduce these changes in Them2(-/-) hepatocytes. In contrast, rates of glucose oxidation and lipogenesis in the presence of high glucose concentrations were decreased only in Them2(-/-) hepatocytes. These findings reveal a primary role for Them2 in promoting mitochondrial oxidation of fatty acids and glucose in the liver.

引用

页码：2396 / 2408

页数：13

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