Document Detail


Acute elevation of plasma lipids does not affect ATP synthesis in human skeletal muscle.
MedLine Citation:
PMID:  20442322     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prolonged elevation of plasma triglycerides and free fatty acids (FFA) reduces insulin-stimulated glucose disposal and myocellular flux through ATP synthase (fATPase). However, the early effects of lipids per se on fATPase are as yet unclear. Thus, this study examined glucose disposal and fATPase during 3 h of FFA elevation in the presence of low plasma insulinemia. Euglycemic pancreatic clamps with low-dose insulin supplementation (6 mU.m body surface area(-2).min(-1)) were performed in eight healthy men with (LIP) or without (CON) lipid infusion to measure whole body glucose disposal. (31)P/(1)H magnetic resonance spectroscopy of calf muscle was applied to quantify fATPase and concentrations of glucose 6-phosphate (G6P), inorganic phosphate (P(i)), phosphocreatine (PCr), ADP, pH, and IMCL before and during the clamps. Lipid infusion increased plasma FFA approximately twofold and decreased glucose disposal by approximately 50% (110-180 min: LIP 0.87 +/- 0.45 vs. CON 1.75 +/- 0.42 mg.kg(-1).min(-1), P = 0.002; means +/- SD). Intramyocellular G6P tended to rise only under control conditions, whereas PCr, ADP, pH, and IMCL remained unchanged from fasting in LIP and CON. Although P(i) concentrations increased by approximately 18%, fATPase remained unchanged from fasting during the clamps (LIP 10.2 +/- 2.2 vs. CON 10.5 +/- 2.6 micromol.g muscle(-1).min(-1), P = not significant). We conclude that 3 h of lipid elevation fail to affect ATP synthesis despite marked reduction of whole body glucose uptake. This suggests that lipid-induced insulin resistance results primarily from mechanisms decreasing glucose uptake rather than from direct interference of fatty acid metabolites with mitochondrial function.
Authors:
A Brehm; M Krssák; A I Schmid; P Nowotny; W Waldhäusl; M Roden
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-04
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  299     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-14     Completed Date:  2010-07-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E33-8     Citation Subset:  IM    
Affiliation:
First Medical Department, Hanusch Hospital, Vienna, Austria.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Diphosphate / metabolism
Adenosine Triphosphatases / metabolism
Adenosine Triphosphate / biosynthesis*,  metabolism
Adult
Cross-Over Studies
Fatty Acids, Nonesterified / blood*
Glucose / metabolism*
Glucose Clamp Technique
Glucosephosphate Dehydrogenase / metabolism
Humans
Insulin Resistance / physiology
Magnetic Resonance Spectroscopy
Male
Muscle, Skeletal / enzymology,  metabolism*
Phosphates / metabolism
Phosphocreatine / metabolism
Random Allocation
Chemical
Reg. No./Substance:
0/Fatty Acids, Nonesterified; 0/Phosphates; 50-99-7/Glucose; 56-65-5/Adenosine Triphosphate; 58-64-0/Adenosine Diphosphate; 67-07-2/Phosphocreatine; EC 1.1.1.49/Glucosephosphate Dehydrogenase; EC 3.6.1.-/Adenosine Triphosphatases

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


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