| First Author | Tang T | Year | 2013 |
| Journal | Cell Metab | Volume | 18 |
| Issue | 6 | Pages | 883-95 |
| PubMed ID | 24268737 | Mgi Jnum | J:206149 |
| Mgi Id | MGI:5548012 | Doi | 10.1016/j.cmet.2013.10.012 |
| Citation | Tang T, et al. (2013) Desnutrin/ATGL activates PPARdelta to promote mitochondrial function for insulin secretion in islet beta cells. Cell Metab 18(6):883-95 |
| abstractText | Excessive caloric intake leading to obesity is associated with insulin resistance and dysfunction of islet beta cells. High-fat feeding decreases desnutrin (also called ATGL/PNPLA2) levels in islets. Here we show that desnutrin ablation via RIP-Cre (betaKO) or RIP-CreER results in hyperglycemia with impaired glucose-stimulated insulin secretion (GSIS). Due to decreased lipolysis, islets have higher TAG content but lower free FA levels. betaKO islets exhibit impaired mitochondrial respiration and lower production of ATP required for GSIS, along with decreased expression of PPARdelta target genes involved in mitochondrial oxidation. Furthermore, synthetic PPARdelta, but not PPARalpha, agonist restores GSIS and expression of mitochondrial oxidative genes in betaKO mice, revealing that desnutrin-catalyzed lipolysis generates PPARdelta ligands. Finally, adenoviral expression of desnutrin in betaKO islets restores all defects of betaKO islet phenotype and function, including GSIS and mitochondrial defects, demonstrating the critical role of the desnutrin-PPARdelta-mitochondrial oxidation axis in regulating islet beta cell GSIS. |
