Document Detail

Fatty acid-induced mitochondrial uncoupling in adipocytes is not a promising target for treatment of insulin resistance unless adipocyte oxidative capacity is increased.
MedLine Citation:
PMID:  18097647     Owner:  NLM     Status:  MEDLINE    
The release of fatty acids from white adipose tissue is regulated at several levels. We have examined the suggestion that fatty acid release might be diminished by upregulation of mitochondrial fatty acid oxidation in the adipocyte, through increasing mitochondrial uncoupling. The intrinsic oxidative capacity of white adipose tissue is low, and older studies suggest that there is little fatty acid oxidation in white adipocytes, human or rodent. We have examined data on fatty acid metabolism and O(2) consumption in human white adipose tissue in vivo, and conclude that increasing fatty acid oxidation within the oxidative capacity of the tissue would produce only small changes (a few percent) in fatty acid release. The major locus of control of fatty acid release beyond the stimulation of lipolysis is the pathway of fatty acid esterification, already probably targeted by the thiazolidinedione insulin-sensitising agents. An alternative approach would be to upregulate the mitochondrial capacity of the adipocyte. We review proof-of-concept studies in which the phenotype of the white adipocyte has been changed to resemble that of the brown adipocyte by expression of peroxisome proliferator-activated receptor coactivator-1alpha. This increases oxidative capacity and also leads to fatty acid retention through upregulation of glycerol-3-phosphate production, and hence increased fatty acid re-esterification. We conclude that prevention or treatment of insulin resistance through alteration of adipocyte fatty acid handling will require more than a simple alteration of the activity of mitochondrial beta-oxidation within normal limits.
K N Frayn; D Langin; F Karpe
Related Documents :
7201097 - Kinetics of carnitine-dependent fatty acid oxidation: implications for human carnitine ...
9469587 - Phytanic acid and pristanic acid are oxidized by sequential peroxisomal and mitochondri...
9661277 - Pretreatment and biodegradability enhancement of dsd acid manufacturing wastewater.
16864897 - Causes and prevention of tamoxifen-induced accumulation of triacylglycerol in rat liver.
22469077 - Evaluation of phototoxic potential of aerial components of the fig tree against human m...
15957927 - Novel pdii-mediated cascade carboxylative annulation to construct benzo[b]furan-3-carbo...
Publication Detail:
Type:  Comment; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-21
Journal Detail:
Title:  Diabetologia     Volume:  51     ISSN:  0012-186X     ISO Abbreviation:  Diabetologia     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-04     Completed Date:  2008-05-21     Revised Date:  2008-08-07    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  394-7     Citation Subset:  IM    
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Adipocytes / drug effects,  physiology*
Adipose Tissue, Brown / physiology
Fatty Acids / pharmacology*
Insulin Resistance / physiology*
Mitochondria / drug effects,  physiology*
Models, Biological
Oxidative Phosphorylation*
Oxygen Consumption
Uncoupling Agents / pharmacology*
Reg. No./Substance:
0/Fatty Acids; 0/Uncoupling Agents
Comment On:
Diabetologia. 2007 Oct;50(10):2036-41   [PMID:  17712547 ]
Comment In:
Diabetologia. 2008 May;51(5):907-8   [PMID:  18317722 ]

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

Previous Document:  Effects of controlled hypoglycaemia on cardiac repolarisation in patients with type 1 diabetes.
Next Document:  USF1 gene variants contribute to metabolic traits in men in a longitudinal 32-year follow-up study.