Dataset Information

PI3K? 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 p110? and p110? subunits in leptin receptor cells (LR??+?) produces a lean phenotype associated with increased energy expenditure, locomotor activity, and thermogenesis. LR??+? mice have deficient growth and delayed puberty. Single subunit deletion (i.e., p110? in LR??) resulted in similarly increased energy expenditure, deficient growth, and pubertal development, but LR?? mice have normal locomotor activity and thermogenesis. Blunted PI3K in leptin receptor (LR) cells enhanced leptin sensitivity in metabolic regulation due to increased basal hypothalamic pAKT, leptin-induced pSTAT3, and decreased PTEN levels. However, these mice are unresponsive to leptin's effects on growth and puberty. We further assessed if these phenotypes were associated with disruption of insulin signaling. LR?InsR mice have no metabolic or growth deficit and show only mild delay in pubertal completion. Our findings demonstrate that PI3K in LR cells plays an essential role in energy expenditure, growth, and reproduction. These actions are independent from insulin signaling.

SUBMITTER: Garcia-Galiano D

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

REPOSITORIES: biostudies-other

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

Garcia-Galiano David D Borges Beatriz C BC Donato Jose J Allen Susan J SJ Bellefontaine Nicole N Wang Mengjie M Zhao Jean J JJ Kozloff Kenneth M KM Hill Jennifer W JW Elias Carol F CF

JCI insight 20171207 23

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 thermogene ...[more]

PMID: 29212950

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PI3K? inactivation in leptin receptor cells increases leptin sensitivity but disrupts growth and reproduction.

Publications

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

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