HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/E252    most recent 00451.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Li, G. Articles by Scarpace, P. J. Search for Related Content PubMed PubMed Citation Articles by Li, G. Articles by Scarpace, P. J.

Melanocortin activation of nucleus of the solitary tract avoids anorectic tachyphylaxis and induces prolonged weight loss

¹Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida; ²Research Service, Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida

Submitted 25 August 2006 ; accepted in final form 26 March 2007

To examine the role of the brain stem melanocortin system in long-term energy regulation, we assessed the effects of overproduction of proopiomelanocortin (POMC) in the caudal brain stem of F344xBN rats with adult-onset obesity. Recombinant adeno-associated viral vector encoding POMC gene was delivered to the nucleus of solitary tract (NTS) in the hindbrain, and food intake, body weight, glucose and fat metabolism, brown adipose tissue thermogenesis, and mRNA levels of neuropeptides and melanocortin receptors were assessed. POMC delivery resulted in sustained reduction in food intake and body weight over 42 days and improved insulin sensitivity. At death, in recombinant adeno-associated viral vector-POMC-treated rats vs. control rats, -melanocyte-stimulating hormone in NTS increased nearly 21-fold, whereas hypothalamic -melanocyte-stimulating hormone remained unchanged. Visceral adiposity decreased by 37%; tissue triglyeride content diminished by 26% and 47% in liver and muscle, respectively; serum triglyeride and nonesterified fatty acids were reduced by 35% and 34%, respectively; phosphorylation of acetyl-CoA carboxylase was elevated by 63% in soleus muscle; brown adipose tissue uncoupling protein 1 increased by 30%; and melanocortin 3 receptor expression declined by 60%, whereas neuropeptide Y, agouti-related protein, and MC4 receptor mRNA levels were unchanged in the NTS. In conclusion, POMC overexpression in the NTS produces a characteristic unabated hypophagia that is uniquely different from the anorexic tachyphylaxis following POMC overexpression in the hypothalamus. The sustained anorectic response may result from absence of compensatory elements in the NTS, such as increased agouti-related protein expression, suggesting melanocortin activation of the brain stem may be a viable strategy to alleviate obesity.

adult-onset obesity; proopiomelanocortin overexpression; gene delivery; brain stem

This article has been cited by other articles:

				T. Babic, R. L. Townsend, L. M. Patterson, G. M. Sutton, H. Zheng, and H.-R. Berthoud Phenotype of neurons in the nucleus of the solitary tract that express CCK-induced activation of the ERK signaling pathway Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2009; 296(4): R845 - R854. [Abstract] [Full Text] [PDF]