| First Author | Hirata M | Year | 2011 |
| Journal | Diabetes | Volume | 60 |
| Issue | 7 | Pages | 1926-37 |
| PubMed ID | 21617180 | Mgi Jnum | J:186749 |
| Mgi Id | MGI:5433003 | Doi | 10.2337/db10-1500 |
| Citation | Hirata M, et al. (2011) Genetic defect in phospholipase Cdelta1 protects mice from obesity by regulating thermogenesis and adipogenesis. Diabetes 60(7):1926-37 |
| abstractText | OBJECTIVE: Regulation of obesity development is an important issue to prevent metabolic syndromes. Gene-disrupted mice of phospholipase Cdelta1 (PLCdelta1), a key enzyme of phosphoinositide turnover, seemed to show leanness. Here we examined whether and how PLCdelta1 is involved in obesity. RESEARCH DESIGN AND METHODS: Weight gain, insulin sensitivity, and metabolic rate in PLCdelta1(-/-) mice were compared with PLCdelta1(+/-) littermate mice on a high-fat diet. Thermogenic and adipogenetic potentials of PLCdelta1(-/-) immortalized brown adipocytes and adipogenesis of PLCdelta1-knockdown (KD) 3T3L1 cells, or PLCdelta1(-/-) white adipose tissue (WAT) stromal-vascular fraction (SVF) cells, were also investigated. RESULTS: PLCdelta1(-/-) mice showed marked decreases in weight gain and mass of epididymal WAT and preserved insulin sensitivity compared with PLCdelta1(+/-) mice on a high-fat diet. In addition, PLCdelta1(-/-) 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 PLCdelta1 was decreased and thermogenic gene uncoupling protein 1 (UCP1) was upregulated to a greater extent in PLCdelta1(-/-) immortalized brown adipocytes. In contrast, ectopic expression of PLCdelta1 in PLCdelta1(-/-) brown adipocytes induced a decrease in UCP expression, indicating that PLCdelta1 negatively regulates thermogenesis. Importantly, accumulation of lipid droplets was severely decreased when PLCdelta1-KD 3T3L1 cells, or PLCdelta1(-/-) WAT SVF cells, were differentiated, whereas differentiation of PLCdelta1(-/-) brown preadipocytes was promoted. CONCLUSIONS: PLCdelta1 has essential roles in thermogenesis and adipogenesis and thereby contributes to the development of obesity. |
