PI3Kα inactivation in leptin receptor cells increases leptin sensitivity but disrupts growth and reproduction.

ABSTRACT: The role of PI3K in leptin physiology has been difficult to determine due to its actions downstream of several metabolic cues, including insulin. Here, we used a series of mouse models to dissociate the roles of specific PI3K catalytic subunits and of insulin receptor (InsR) downstream of leptin signaling. We show that disruption of p110α and p110β subunits in leptin receptor cells (LRΔα+β) produces a lean phenotype associated with increased energy expenditure, locomotor activity, and thermogenesis. LRΔα+β mice have deficient growth and delayed puberty. Single subunit deletion (i.e., p110α in LRΔα) resulted in similarly increased energy expenditure, deficient growth, and pubertal development, but LRΔα mice have normal locomotor activity and thermogenesis. Blunted PI3K in leptin receptor (L

SUBMITTER: Garcia-Galiano D 

PROVIDER: S-EPMC5752267 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature