| First Author | Stump M | Year | 2016 |
| Journal | Physiol Genomics | Volume | 48 |
| Issue | 7 | Pages | 491-501 |
| PubMed ID | 27199455 | Mgi Jnum | J:242422 |
| Mgi Id | MGI:5905220 | Doi | 10.1152/physiolgenomics.00032.2016 |
| Citation | Stump M, et al. (2016) Effect of selective expression of dominant-negative PPARgamma in pro-opiomelanocortin neurons on the control of energy balance. Physiol Genomics 48(7):491-501 |
| abstractText | Peroxisome proliferator-activated receptor-gamma (PPARgamma), a master regulator of adipogenesis, was recently shown to affect energy homeostasis through its actions in the brain. Deletion of PPARgamma in mouse brain, and specifically in the pro-opiomelanocortin (POMC) neurons, results in resistance to diet-induced obesity. To study the mechanisms by which PPARgamma in POMC neurons controls energy balance, we constructed a Cre-recombinase-dependent conditionally activatable transgene expressing either wild-type (WT) or dominant-negative (P467L) PPARgamma and the tdTomato reporter. Inducible expression of both forms of PPARgamma was validated in cells in culture, in liver of mice infected with an adenovirus expressing Cre-recombinase (AdCre), and in the brain of mice expressing Cre-recombinase either in all neurons (NES(Cre)/PPARgamma-P467L) or selectively in POMC neurons (POMC(Cre)/PPARgamma-P467L). Whereas POMC(Cre)/PPARgamma-P467L mice exhibited a normal pattern of weight gain when fed 60% high-fat diet, they exhibited increased weight gain and fat mass accumulation in response to a 10% fat isocaloric-matched control diet. POMC(Cre)/PPARgamma-P467L mice were leptin sensitive on control diet but became leptin resistant when fed 60% high-fat diet. There was no difference in body weight between POMC(Cre)/PPARgamma-WT mice and controls in response to 60% high-fat diet. However, POMC(Cre)/PPARgamma-WT, but not POMC(Cre)/PPARgamma-P467L, mice increased body weight in response to rosiglitazone, a PPARgamma agonist. These observations support the concept that alterations in PPARgamma-driven mechanisms in POMC neurons can play a role in the regulation of metabolic homeostasis under certain dietary conditions. |
