Genetic Defect in Phospholipase Cδ1 Protects Mice From Obesity by Regulating Thermogenesis and Adipogenesis

被引：34

作者：

Hirata, Masayuki ^{[1
]}

Suzuki, Mutsumi ^{[1
]}

Ishii, Rika ^{[1
]}

Satow, Reiko ^{[1
]}

Uchida, Takafumi ^{[1
]}

Kitazumi, Tomoya ^{[2
]}

Sasaki, Tsutomu ^{[2
]}

Kitamura, Tadahiro ^{[2
]}

Yamaguchi, Hideki ^{[3
,4
]}

Nakamura, Yoshikazu ^{[1
]}

Fukami, Kiyoko ^{[1
]}

机构：

[1] Tokyo Univ Pharm & Life Sci, Lab Genome & Biosignal, Tokyo, Japan

[2] Metabol Signal Res Ctr, Inst Mol & Cellular Regulat, Maebashi, Gunma, Japan

[3] Natl Canc Ctr, Res Inst, Growth Factor Div, Chuo Ku, Tokyo 104, Japan

[4] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama, Japan

来源：

DIABETES | 2011年 / 60卷 / 07期

关键词：

INSULIN-SECRETION; ENERGY-BALANCE; GLUCOSE; ROLES; ADIPOCYTES; RECEPTORS; UCP1;

D O I：

10.2337/db10-1500

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

OBJECTIVE-Regulation of obesity development is an important issue to prevent metabolic syndromes. Gene-disrupted mice of phospholipase C delta 1 (PLC delta 1), a key enzyme of phosphoinositide turnover, seemed to show leanness. Here we examined whether and how PLC delta 1 is involved in obesity. RESEARCH DESIGN AND METHODS-Weight gain, insulin sensitivity, and metabolic rate in PLC delta 1(-/-) mice were compared with PLC delta 1(+/-) littermate mice on a high-fat diet. Therrnogenic and adipogenetic potentials of PLC delta 1(-/-) immortalized brown adipocytes and adipogenesis of PLC delta 1-knockdown (KD) 3T3L1 cells, or PLC delta 1(-/-) white adipose tissue (WAT) stromal-vascular fraction (SVF) cells, were also investigated. RESULTS-PLC delta 1(-/-) mice showed marked decreases in weight gain and mass of epididymal WAT and preserved insulin sensitivity compared with PLC delta 1(+/-) mice on a high-fat diet. In addition, PLC delta 1(-/-) mice have a higher metabolic rate such as higher oxygen consumption and heat production. When control immortalized brown adipocytes were treated with thermogenic inducers, expression of PLC delta 1 was decreased and therrnogenic gene uncoupling protein 1 (UCP1) was upregulated to a greater extent in PLC delta 1(-/-) immortalized brown adipocytes. In contrast, ectopic expression of PLC delta 1 in PLC delta 1(-/-) brown adipocytes induced a decrease in UCP expression, indicating that PLC delta 1 negatively regulates thermogenesis. Importantly, accumulation of lipid droplets was severely decreased when PLC delta 1-KD 3T3L1 cells, or PLC delta 1(-/-) WAT SVF cells, were differentiated, whereas differentiation of PLC delta 1(-/-) brown preadipocytes was promoted. CONCLUSIONS-PLC delta 1 has essential roles in thermogenesis and adipogenesis and thereby contributes to the development of obesity. Diabetes 60:1926-1937, 2011

引用

页码：1926 / 1937

页数：12

共 42 条

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