Document Detail


Deficiency of lipoprotein lipase in neurons modifies the regulation of energy balance and leads to obesity.
MedLine Citation:
PMID:  21195353     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Free fatty acids (FFAs) suppress appetite when injected into the hypothalamus. To examine whether lipoprotein lipase (LPL), a serine hydrolase that releases FFAs from circulating triglyceride (TG)-rich lipoproteins, might contribute to FFA-mediated signaling in the brain, we created neuron-specific LPL-deficient mice. Homozygous mutant (NEXLPL-/-) mice were hyperphagic and became obese by 16 weeks of age. These traits were accompanied by elevations in the hypothalamic orexigenic neuropeptides, AgRP and NPY, and were followed by reductions in metabolic rate. The uptake of TG-rich lipoprotein fatty acids was reduced in the hypothalamus of 3-month-old NEXLPL-/- mice. Moreover, deficiencies in essential fatty acids in the hypothalamus were evident by 3 months, with major deficiencies of long-chain n-3 fatty acids by 12 months. These results indicate that TG-rich lipoproteins are sensed in the brain by an LPL-dependent mechanism and provide lipid signals for the central regulation of body weight and energy balance.
Authors:
Hong Wang; Giuseppe Astarita; Matthew D Taussig; Kalyani G Bharadwaj; Nicholas V DiPatrizio; Klaus-Armin Nave; Daniele Piomelli; Ira J Goldberg; Robert H Eckel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell metabolism     Volume:  13     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-03     Completed Date:  2011-02-10     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  105-13     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / metabolism
Energy Intake
Energy Metabolism
Fatty Acids, Nonesterified / metabolism
Female
Gene Expression
Hypothalamus / metabolism
Lipoprotein Lipase / deficiency*,  genetics,  metabolism
Lipoproteins / metabolism
Male
Mice
Mice, Obese
Mice, Transgenic
Neurons / enzymology*
Obesity / enzymology*,  genetics,  metabolism,  pathology
Grant Support
ID/Acronym/Agency:
DK073955/DK/NIDDK NIH HHS; DK42266/DK/NIDDK NIH HHS; HL45095/HL/NHLBI NIH HHS; P30DK048520/DK/NIDDK NIH HHS; R01 DK042266/DK/NIDDK NIH HHS; R01 DK042266-10/DK/NIDDK NIH HHS; R01 DK073955/DK/NIDDK NIH HHS; R01 DK073955-04/DK/NIDDK NIH HHS; R01 DK089309/DK/NIDDK NIH HHS; R01 HL045095/HL/NHLBI NIH HHS; R01 HL045095-21/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids, Nonesterified; 0/Lipoproteins; EC 3.1.1.34/Lipoprotein Lipase
Comments/Corrections

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