| First Author | Felsted JA | Year | 2017 |
| Journal | Cell Rep | Volume | 21 |
| Issue | 10 | Pages | 2737-2747 |
| PubMed ID | 29212022 | Mgi Jnum | J:254839 |
| Mgi Id | MGI:6104012 | Doi | 10.1016/j.celrep.2017.11.048 |
| Citation | Felsted JA, et al. (2017) Alpha2delta-1 in SF1(+) Neurons of the Ventromedial Hypothalamus Is an Essential Regulator of Glucose and Lipid Homeostasis. Cell Rep 21(10):2737-2747 |
| abstractText | The central mechanisms controlling glucose and lipid homeostasis are inadequately understood. We show that alpha2delta-1 is an essential regulator of glucose and lipid balance, acting in steroidogenic factor-1 (SF1) neurons of the ventromedial hypothalamus (VMH). These effects are body weight independent and involve regulation of SF1(+) neuronal activity and sympathetic output to metabolic tissues. Accordingly, mice with alpha2delta-1 deletion in SF1 neurons exhibit glucose intolerance, altered lipolysis, and decreased cholesterol content in adipose tissue despite normal energy balance regulation. Profound reductions in the firing rate of SF1 neurons, decreased sympathetic output, and elevated circulating levels of serotonin are associated with these alterations. Normal calcium currents but reduced excitatory postsynaptic currents in mutant SF1 neurons implicate alpha2delta-1 in the promotion of excitatory synaptogenesis separate from its canonical role as a calcium channel subunit. Collectively, these findings identify an essential mechanism that regulates VMH neuronal activity and glycemic and lipid control and may be a target for tackling metabolic disease. |
