| First Author | Fisette A | Year | 2016 |
| Journal | Cell Rep | Volume | 17 |
| Issue | 5 | Pages | 1217-1226 |
| PubMed ID | 27783937 | Mgi Jnum | J:240809 |
| Mgi Id | MGI:5896464 | Doi | 10.1016/j.celrep.2016.10.004 |
| Citation | Fisette A, et al. (2016) alpha/beta-Hydrolase Domain 6 in the Ventromedial Hypothalamus Controls Energy Metabolism Flexibility. Cell Rep 17(5):1217-1226 |
| abstractText | alpha/beta-Hydrolase domain 6 (ABHD6) is a monoacylglycerol hydrolase that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG). Although complete or peripheral ABHD6 loss of function is protective against diet-induced obesity and insulin resistance, the role of ABHD6 in the central control of energy balance is unknown. Using a viral-mediated knockout approach, targeted endocannabinoid measures, and pharmacology, we discovered that mice lacking ABHD6 from neurons of the ventromedial hypothalamus (VMHKO) have higher VMH 2-AG levels in conditions of endocannabinoid recruitment and fail to physiologically adapt to key metabolic challenges. VMHKO mice exhibited blunted fasting-induced feeding and reduced food intake, energy expenditure, and adaptive thermogenesis in response to cold exposure, high-fat feeding, and dieting (transition to a low-fat diet). Our findings identify ABHD6 as a regulator of the counter-regulatory responses to major metabolic shifts, including fasting, nutrient excess, cold, and dieting, thereby highlighting the importance of ABHD6 in the VMH in mediating energy metabolism flexibility. |
