Postnatal Ablation of POMC Neurons Induces an Obese Phenotype Characterized by Decreased Food Intake and Enhanced Anxiety-Like Behavior

• DOI: 10.1210/me.2012-1344
• Publication Date: 2013-05-15T23:32:02Z
• Authors: Yona Greenman; Yael Kuperman; Yonat Drori; Sylvia L. Asa; Inbal Navon; Oren Forkosh; Shosh Gil; Naftali Stern; Alon Chen
• Keywords: Proopiomelanocortin; Energy homeostasis; Corticosterone

Proopiomelanocortin (POMC) neurons in the arcuate nucleus of hypothalamus are central components systems regulating appetite and energy homeostasis. Here we report on establishment a mouse model which ribonuclease III Dicer-1 has been specifically deleted from POMC-expressing (POMC(ΔDCR)), leading to postnatal cell death. Mice born phenotypically normal, at expected genetic ratio with normal hypothalamic POMC-mRNA levels. At 6 weeks age, no POMC neurons/cells could be detected either or pituitary POMC(ΔDCR) mice. develop progressive obesity secondary decreased expenditure but unrelated food intake, was surprisingly lower than control Reduced expression AgRP ghrelin receptor reduced uncoupling protein 1 brown adipose tissue can potentially explain intake heat production, respectively, these Fasting glucose levels were dramatically elevated mice tolerance test revealed marked intolerance Secondary corticotrope ablation, basal stress-induced corticosterone undetectable Despite this lack activation neuroendocrine stress response, exhibited an anxiogenic phenotype, accompanied corticotropin-releasing factor arginine-vasopressin transcripts. In conclusion, ablation leads enhanced anxiety development despite glucocorticoid deficiency.