Document Detail


Knockdown of NPY expression in the dorsomedial hypothalamus promotes development of brown adipocytes and prevents diet-induced obesity.
MedLine Citation:
PMID:  21531339     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypothalamic neuropeptide Y (NPY) has been implicated in control of energy balance, but the physiological importance of NPY in the dorsomedial hypothalamus (DMH) remains unclear. Here we report that knockdown of NPY expression in the DMH by adeno-associated virus-mediated RNAi reduced fat depots in rats fed regular chow and ameliorated high-fat diet-induced hyperphagia and obesity. DMH NPY knockdown resulted in development of brown adipocytes in inguinal white adipose tissue through the sympathetic nervous system. This knockdown increased uncoupling protein 1 expression in both inguinal fat and interscapular brown adipose tissue (BAT). Consistent with the activation of BAT, DMH NPY knockdown increased energy expenditure and enhanced the thermogenic response to a cold environment. This knockdown also increased locomotor activity, improved glucose homeostasis, and enhanced insulin sensitivity. Together, these results demonstrate critical roles of DMH NPY in body weight regulation through affecting food intake, body adiposity, thermogenesis, energy expenditure, and physical activity.
Authors:
Pei-Ting Chao; Liang Yang; Susan Aja; Timothy H Moran; Sheng Bi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cell metabolism     Volume:  13     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-02     Completed Date:  2011-09-05     Revised Date:  2012-05-07    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  573-83     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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MeSH Terms
Descriptor/Qualifier:
Adipocytes, Brown / cytology*,  metabolism
Adipose Tissue, White / cytology,  metabolism
Animals
Body Weight*
Cells, Cultured
Dependovirus / genetics
Diet, Atherogenic*
Down-Regulation
Eating
Energy Metabolism
Glucose / metabolism
Glucose Tolerance Test
Homeostasis
Hypothalamus / metabolism*
Immunoblotting
Insulin / pharmacology
Ion Channels / genetics,  metabolism
Male
Mitochondrial Proteins / genetics,  metabolism
Neuropeptide Y / physiology*
Obesity / etiology,  metabolism,  prevention & control*
RNA, Messenger / genetics
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Grant Support
ID/Acronym/Agency:
DK074269/DK/NIDDK NIH HHS; R01 DK074269-01A1/DK/NIDDK NIH HHS; R01 DK074269-02/DK/NIDDK NIH HHS; R01 DK074269-03/DK/NIDDK NIH HHS; R01 DK074269-04/DK/NIDDK NIH HHS; R01 DK074269-04S1/DK/NIDDK NIH HHS; R01 DK074269-05/DK/NIDDK NIH HHS; R01 DK087888-02/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Insulin; 0/Ion Channels; 0/Mitochondrial Proteins; 0/Neuropeptide Y; 0/RNA, Messenger; 0/mitochondrial uncoupling protein; 50-99-7/Glucose
Comments/Corrections
Comment In:
Cell Metab. 2011 May 4;13(5):493-4   [PMID:  21531331 ]

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