Dataset Information

Genetic defect in phospholipase C?1 protects mice from obesity by regulating thermogenesis and adipogenesis.

ABSTRACT:

Objective

Regulation of obesity development is an important issue to prevent metabolic syndromes. Gene-disrupted mice of phospholipase C?1 (PLC?1), a key enzyme of phosphoinositide turnover, seemed to show leanness. Here we examined whether and how PLC?1 is involved in obesity.

Research design and methods

Weight gain, insulin sensitivity, and metabolic rate in PLC?1(-/-) mice were compared with PLC?1(+/-) littermate mice on a high-fat diet. Thermogenic and adipogenetic potentials of PLC?1(-/-) immortalized brown adipocytes and adipogenesis of PLC?1-knockdown (KD) 3T3L1 cells, or PLC?1(-/-) white adipose tissue (WAT) stromal-vascular fraction (SVF) cells, were also investigated.

Results

PLC?1(-/-) mice showed marked decreases in weight gain and mass of epididymal WAT and preserved insulin sensitivity compared with PLC?1(+/-) mice on a high-fat diet. In addition, PLC?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?1 was decreased and thermogenic gene uncoupling protein 1 (UCP1) was upregulated to a greater extent in PLC?1(-/-) immortalized brown adipocytes. In contrast, ectopic expression of PLC?1 in PLC?1(-/-) brown adipocytes induced a decrease in UCP expression, indicating that PLC?1 negatively regulates thermogenesis. Importantly, accumulation of lipid droplets was severely decreased when PLC?1-KD 3T3L1 cells, or PLC?1(-/-) WAT SVF cells, were differentiated, whereas differentiation of PLC?1(-/-) brown preadipocytes was promoted.

Conclusions

PLC?1 has essential roles in thermogenesis and adipogenesis and thereby contributes to the development of obesity.

SUBMITTER: Hirata M

PROVIDER: S-EPMC3121440 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Publications

Genetic defect in phospholipase Cδ1 protects mice from obesity by regulating thermogenesis and adipogenesis.

Hirata Masayuki M Suzuki Mutsumi M Ishii Rika R Satow Reiko R Uchida Takafumi T Kitazumi Tomoya T Sasaki Tsutomu T Kitamura Tadahiro T Yamaguchi Hideki H Nakamura Yoshikazu Y Fukami Kiyoko K

Diabetes 20110526 7

<h4>Objective</h4>Regulation of obesity development is an important issue to prevent metabolic syndromes. Gene-disrupted mice of phospholipase Cδ1 (PLCδ1), a key enzyme of phosphoinositide turnover, seemed to show leanness. Here we examined whether and how PLCδ1 is involved in obesity.<h4>Research design and methods</h4>Weight gain, insulin sensitivity, and metabolic rate in PLCδ1(-/-) mice were compared with PLCδ1(+/-) littermate mice on a high-fat diet. Thermogenic and adipogenetic potentials ...[more]

PMID: 21617180

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