Document Detail


Simultaneous POMC gene transfer to hypothalamus and brainstem increases physical activity, lipolysis and reduces adult-onset obesity.
MedLine Citation:
PMID:  21366729     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pro-opiomelanocortin (POMC) neurons are identified in two brain sites, the arcuate nucleus of the hypothalamus and nucleus of the solitary tract (NTS) in brainstem. Earlier pharmacological and POMC gene transfer studies demonstrate that melanocortin activation in either site alone improves insulin sensitivity and reduces obesity. The present study, for the first time, investigated the long-term efficacy of POMC gene transfer concurrently into both sites in the regulation of energy metabolism in aged F344xBN rats bearing adult-onset obesity. Pair feeding was included to reveal food-independent POMC impact on energy expenditure. We introduced adeno-associated virus encoding either POMC or green fluorescence protein to the two brain areas in 22-month-old rats, then recorded food intake and body weight, assessed oxygen consumption, serum leptin, insulin and glucose, tested voluntary wheel running, analysed POMC expression, and examined fat metabolism in brown and white adipose tissues. POMC mRNA was significantly increased in both the hypothalamus and NTS region at termination. Relative to pair feeding, POMC caused sustained weight reduction and additional fat loss, lowered fasting insulin and glucose, and augmented white fat hormone-sensitive lipase activity and brown fat uncoupling protein 1 level. By wheel running assessment, the POMC animals ran twice the distance as the Control or pair-fed rats. Thus, the dual-site POMC treatment ameliorated adult-onset obesity effectively, involving a moderate hypophagia lasting ∼60 days, enhanced lipolysis and thermogenesis, and increased physical activity in the form of voluntary wheel running. The latter finding provides a clue for countering age-related decline in physical activity.
Authors:
Yi Zhang; Enda Rodrigues; Gang Li; Yongxin Gao; Michael King; Christy S Carter; Nihal Tumer; Kit-Yan Cheng; Philip J Scarpace
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-03-02
Journal Detail:
Title:  The European journal of neuroscience     Volume:  33     ISSN:  1460-9568     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-18     Completed Date:  2011-09-16     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  France    
Other Details:
Languages:  eng     Pagination:  1541-50     Citation Subset:  IM    
Copyright Information:
European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. No claim to original US government works.
Affiliation:
Malcom Randall Veterans Affairs Medical Center, Gainesville, FL 32608, USA. yizhang@ufl.edu
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MeSH Terms
Descriptor/Qualifier:
Aging / physiology
Animals
Arcuate Nucleus / physiology*
Blood Glucose / metabolism
Body Weight
Dependovirus / genetics,  metabolism
Eating
Energy Metabolism
Gene Transfer Techniques*
Humans
Insulin / blood
Leptin / blood
Lipolysis / physiology*
Male
Motor Activity / physiology*
Obesity / physiopathology*
Pro-Opiomelanocortin / genetics*,  metabolism
Rats
Rats, Inbred F344
Solitary Nucleus / physiology*
Grant Support
ID/Acronym/Agency:
1 P30 AG028740/AG/NIA NIH HHS; AG026159/AG/NIA NIH HHS; AG20985/AG/NIA NIH HHS; R01 AG026159/AG/NIA NIH HHS; R01 AG026159-04/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Insulin; 0/Leptin; 66796-54-1/Pro-Opiomelanocortin
Comments/Corrections

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