Ablation of PI3Kγ in neurons protects mice from diet-induced obesity MASLD and insulin resistance.

ABSTRACT: Mice with genetic ablation of PI3Kγ are protected from diet-induced obesity. However, the cell type responsible for PI3Kγ action in obesity remains unknown. We generated mice with conditional deletion of PI3Kγ in neurons using the nestin promoter to drive the expression of the Cre recombinase (PI3Kγ^Nest mice) and investigated their metabolic phenotype in a model of diet-induced obesity. On a chow diet, lean PI3Kγ^Nest mice display reduced linear growth and a normal metabolic phenotype. PI3Kγ^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

SUBMITTER: Molinaro A 

PROVIDER: S-EPMC11732162 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature