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Diabetes. 2017 Apr;66(4):920-934. doi: 10.2337/db16-0482. Epub 2017 Jan 10.

Deletion of Protein Kinase C λ in POMC Neurons Predisposes to Diet-Induced Obesity.

Author information

1
UW Diabetes Institute and Department of Medicine, University of Washington, Seattle, WA.
2
Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL.
3
Research & Internal Medicine Services, James A. Haley VA Medical Center, Tampa, FL.
4
The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway.
5
UW Diabetes Institute and Department of Medicine, University of Washington, Seattle, WA jpthaler@uw.edu.

Abstract

Effectors of the phosphoinositide 3-kinase (PI3K) signal transduction pathway contribute to the hypothalamic regulation of energy and glucose homeostasis in divergent ways. Here we show that central nervous system (CNS) action of the PI3K signaling intermediate atypical protein kinase C (aPKC) constrains food intake, weight gain, and glucose intolerance in both rats and mice. Pharmacological inhibition of CNS aPKC activity acutely increases food intake and worsens glucose tolerance in chow-fed rodents and causes excess weight gain during high-fat diet (HFD) feeding. Similarly, selective deletion of the aPKC isoform Pkc-λ in proopiomelanocortin (POMC) neurons disrupts leptin action, reduces melanocortin content in the paraventricular nucleus, and markedly increases susceptibility to obesity, glucose intolerance, and insulin resistance specifically in HFD-fed male mice. These data implicate aPKC as a novel regulator of energy and glucose homeostasis downstream of the leptin-PI3K pathway in POMC neurons.

PMID:
28073831
PMCID:
PMC5360303
DOI:
10.2337/db16-0482
[Indexed for MEDLINE]
Free PMC Article

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