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

Overview

Journal Diabetes

Specialty Endocrinology

Date 2017 Jan 12

PMID 28073831

Citations 10

Authors

Mauricio D Dorfman

Jordan E Krull

Jarrad M Scarlett

Stephan J Guyenet

Mini P Sajan

Vincent Damian

Hong T Nguyen

Michael Leitges

Gregory J Morton

Robert V Farese

Michael W Schwartz

Joshua P Thaler

Affiliations

Soon will be listed here.

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 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.

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