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- Title
Deletion of Protein Kinase C λ in POMC Neurons Predisposes to Diet-Induced Obesity.
- Authors
Dorfman, Mauricio D.; Krull, Jordan E.; Scarlett, Jarrad M.; Guyenet, Stephan J.; Sajan, Mini P.; Damian, Vincent; Nguyen, Hong T.; Leitges, Michael; Morton, Gregory J.; Farese, Robert V.; Schwartz, Michael W.; Thaler, Joshua P.
- 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.
- Subjects
PHOSPHOINOSITIDES; NEURONS; PROTEIN kinases; CENTRAL nervous system; PROTEIN kinase C; OBESITY; GLUCOSE intolerance; INSULIN resistance; GLUCOSE metabolism; ANIMAL experimentation; CELLULAR signal transduction; DIET; ENERGY metabolism; HYPOTHALAMUS; INGESTION; ISOENZYMES; MICE; PHOSPHOTRANSFERASES; PROTEIN precursors; RATS; RESEARCH funding; TRANSFERASES; WEIGHT gain; LEPTIN
- Publication
Diabetes, 2017, Vol 66, Issue 4, p920
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db16-0482