Document Detail

The regulation of hepatic carbon flux by pyruvate dehydrogenase and pyruvate dehydrogenase kinase during long-term food restriction.
MedLine Citation:
PMID:  8250846     Owner:  NLM     Status:  MEDLINE    
The present study investigated the effects of chronic food restriction (achieved by limiting access to food to 2 h daily for up to 8 weeks) on the activity of the active form of pyruvate dehydrogenase (PDHa) in liver. Accelerated and exaggerated activation of hepatic PDH in response to a meal, previously demonstrated to occur within 10 days of food restriction, was demonstrated to persist for 4 and 8 weeks of food restriction, despite a food intake of only 50-60% of controls. Activation of hepatic PDH during feeding in rats subjected to food restriction for 4 weeks was dependent on continued food intake. As a consequence, hepatic PDHa activities in food-restricted rats were suppressed relative to controls for 19 h of the 24 h daily cycle. Curve-fitting by second-order polynomial regression analysis demonstrated a significant positive correlation between hepatic PDHa activity and lipogenic rate over the range of PDHa activities observed during the 2 h feeding period. Increased lipogenesis during feeding in food-restricted rats was not at the expense of hepatic glycogen synthesis or deposition; measurement of concurrent rates of glycogenesis and lipogenesis revealed simultaneous flux through both pathways, but specific activation of lipogenesis. The accelerated re-activation of hepatic PDH observed within 1 h of feeding in rats subjected to 4 weeks of food restriction was facilitated by a failure of the 22 h interprandial fasting period to induce a stable increase in hepatic PDH kinase activity. The present study indicates differential regulation of hepatic PDH kinase activity during periods of food withdrawal between food-restricted rats and starved/re-fed control rats. Such regulation occupies a critical role in determining the rate of activation of hepatic PDH during feeding. In turn, increased activity of hepatic PDHa during feeding in food-restricted rats bears a close positive relationship with hepatic lipogenic rate.
M C Sugden; R M Grimshaw; M J Holness
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  296 ( Pt 1)     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1993 Nov 
Date Detail:
Created Date:  1993-12-29     Completed Date:  1993-12-29     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  217-23     Citation Subset:  IM    
Department of Biochemistry, Faculty of Basic Medical Sciences, Queen Mary & Westfield College, University of London, U.K.
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MeSH Terms
Diet, Reducing
Lipids / biosynthesis
Liver / enzymology,  metabolism*
Liver Glycogen / metabolism*
Protein Kinases / metabolism*
Protein-Serine-Threonine Kinases
Pyruvate Dehydrogenase Complex / metabolism*
Rats, Wistar
Regression Analysis
Time Factors
Reg. No./Substance:
0/Lipids; 0/Liver Glycogen; 0/Pyruvate Dehydrogenase Complex; EC 2.7.-/Protein Kinases; EC Kinases; EC dehydrogenase (acetyl-transferring) kinase

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