| First Author | Zhang Y | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 33 | Pages | 20149-20158 |
| PubMed ID | 32747560 | Mgi Jnum | J:293753 |
| Mgi Id | MGI:6451828 | Doi | 10.1073/pnas.2004392117 |
| Citation | Zhang Y, et al. (2020) Hypothalamic extended synaptotagmin-3 contributes to the development of dietary obesity and related metabolic disorders. Proc Natl Acad Sci U S A 117(33):20149-20158 |
| abstractText | The C2 domain containing protein extended synaptotagmin (E-Syt) plays important roles in both lipid homeostasis and the intracellular signaling; however, its role in physiology remains largely unknown. Here, we show that hypothalamic E-Syt3 plays a critical role in diet-induced obesity (DIO). E-Syt3 is characteristically expressed in the hypothalamic nuclei. Whole-body or proopiomelanocortin (POMC) neuron-specific ablation of E-Syt3 ameliorated DIO and related comorbidities, including glucose intolerance and dyslipidemia. Conversely, overexpression of E-Syt3 in the arcuate nucleus moderately promoted food intake and impaired energy expenditure, leading to increased weight gain. Mechanistically, E-Syt3 ablation led to increased processing of POMC to alpha-melanocyte-stimulating hormone (alpha-MSH), increased activities of protein kinase C and activator protein-1, and enhanced expression of prohormone convertases. These findings reveal a previously unappreciated role for hypothalamic E-Syt3 in DIO and related metabolic disorders. |
