Document Detail


Lipin deficiency impairs diurnal metabolic fuel switching.
MedLine Citation:
PMID:  17130489     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fatty liver is a common feature of both obesity and lipodystrophy, reflecting compromised adipose tissue function. The lipin-deficient fatty liver dystrophy (fld) mouse is an exception, as there is lipodystrophy without a fatty liver. Using a combination of indirect calorimetry and stable-isotope flux phenotyping, we determined that fld mice exhibit abnormal fuel utilization throughout the diurnal cycle, with increased glucose oxidation near the end of the fasting period and increased fatty acid oxidation during the feeding period. The mechanisms underlying these alterations include a twofold increase compared with wild-type mice in tissue glycogen storage during the fed state, a 40% reduction in hepatic glucose production in the fasted state, and a 27-fold increase in de novo fatty acid synthesis in liver during the fed state. Thus, the inability to store energy in adipose tissue in the fld mouse leads to a compensatory increase in glycogen storage for use during the fasting period and reliance upon hepatic fatty acid synthesis to provide fuel for peripheral tissues during the fed state. The increase in hepatic fatty acid synthesis and peripheral utilization provides a potential mechanism to ameliorate fatty liver in the fld that would otherwise occur as a consequence of adipose tissue dysfunction.
Authors:
Jun Xu; W N Paul Lee; Jack Phan; Mohammed F Saad; Karen Reue; Irwin J Kurland
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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:  Diabetes     Volume:  55     ISSN:  0012-1797     ISO Abbreviation:  Diabetes     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-28     Completed Date:  2007-01-16     Revised Date:  2012-01-10    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3429-38     Citation Subset:  AIM; IM    
Affiliation:
State University of New York at Stony Brook, HSC T-15 Room 060, Stony Brook, NY 11794-8154, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Calorimetry, Indirect
Circadian Rhythm*
DNA Primers
Energy Metabolism*
Fatty Acid Synthetase Complex / metabolism
Fatty Liver / genetics
Glycogen / metabolism
Liver / enzymology
Mice
Mice, Inbred BALB C
Mice, Knockout
Nuclear Proteins / deficiency*,  genetics
Grant Support
ID/Acronym/Agency:
DK58132/DK/NIDDK NIH HHS; HL28481/HL/NHLBI NIH HHS; R01 DK058132-07/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Nuclear Proteins; 9005-79-2/Glycogen; EC 3.1.3.4/Lpin1 protein, mouse; EC 6.-/Fatty Acid Synthetase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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