| First Author | Molinaro A | Year | 2025 |
| Journal | iScience | Volume | 28 |
| Issue | 1 | Pages | 111562 |
| PubMed ID | 39811649 | Mgi Jnum | J:363354 |
| Mgi Id | MGI:7854734 | Doi | 10.1016/j.isci.2024.111562 |
| Citation | Molinaro A, et al. (2025) Ablation of PI3Kgamma in neurons protects mice from diet-induced obesity MASLD and insulin resistance. iScience 28(1):111562 |
| abstractText | Mice with genetic ablation of PI3Kgamma are protected from diet-induced obesity. However, the cell type responsible for PI3Kgamma action in obesity remains unknown. We generated mice with conditional deletion of PI3Kgamma in neurons using the nestin promoter to drive the expression of the Cre recombinase (PI3Kgamma(Nest) mice) and investigated their metabolic phenotype in a model of diet-induced obesity. On a chow diet, lean PI3Kgamma(Nest) mice display reduced linear growth and a normal metabolic phenotype. PI3Kgamma(Nest) mice were largely protected from diet-induced obesity and liver steatosis and showed improved glucose tolerance and insulin sensitivity. This phenotype was associated with increased phosphorylation of hormone-sensitive lipase (HSL) at protein kinase A (PKA) sites in white fat. It is concluded that PI3Kgamma action in diet-induced obesity depends on its activity in neurons controlling adipose tissue lipolysis. Future clinical studies on PI3Kgamma inhibitors capable of crossing the brain-blood barrier will reveal the relevance of these findings to humans. |
