| First Author | Stump M | Year | 2016 |
| Journal | Endocrinology | Volume | 157 |
| Issue | 11 | Pages | 4266-4275 |
| PubMed ID | 27575030 | Mgi Jnum | J:240435 |
| Mgi Id | MGI:5883392 | Doi | 10.1210/en.2016-1524 |
| Citation | Stump M, et al. (2016) Nervous System Expression of PPARgamma and Mutant PPARgamma Has Profound Effects on Metabolic Regulation and Brain Development. Endocrinology 157(11):4266-4275 |
| abstractText | Peroxisome proliferator activated receptor (PPARgamma) is a nuclear receptor transcription factor that regulates adipogenesis and energy homeostasis. Recent studies suggest PPARgamma may mediate some of its metabolic effects through actions in the brain. We used a Cre-recombinase-dependent (using NestinCre) conditionally activatable transgene expressing either wild-type (WT) or dominant-negative (P467L) PPARgamma to examine mechanisms by which PPARgamma in the nervous system controls energy balance. Inducible expression of PPARgamma was evident throughout the brain. Expression of 2 PPARgamma target genes, aP2 and CD36, was induced by WT but not P467L PPARgamma in the brain. Surprisingly, NesCre/PPARgamma-WT mice exhibited severe microcephaly and brain malformation, suggesting that PPARgamma can modulate brain development. On the contrary, NesCre/PPARgamma-P467L mice exhibited blunted weight gain to high-fat diet, which correlated with a decrease in lean mass and tissue masses, accompanied by elevated plasma GH, and depressed plasma IGF-1, indicative of GH resistance. There was no expression of the transgene in the pancreas but both fasting plasma glucose, and fed and fasted plasma insulin levels were markedly decreased. NesCre/PPARgamma-P467L mice fed either control diet or high-fat diet displayed impaired glucose tolerance yet exhibited increased sensitivity to exogenous insulin and increased insulin receptor signaling in white adipose tissue, liver, and skeletal muscle. These observations support the concept that alterations in PPARgamma-driven mechanisms in the nervous system play a role in the regulation of growth and glucose metabolic homeostasis. |
