Document Detail


Effects of rosiglitazone and linoleic acid on human preadipocyte differentiation.
MedLine Citation:
PMID:  12814394     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Peroxisome proliferator activated receptor gamma (PPARgamma) is a ligand-activated transcription factor known to be central to both adipose tissue development and insulin action. Growth of adipose tissue requires differentiation of preadipocytes with acquisition of specific cellular functions including insulin sensitivity, leptin secretion and the capacity to store triglyceride. Dietary fatty acids and members of the thiazolidinedione class of compounds have been reported to influence adipogenesis at the transcriptional level. Here, we compare the effects of a dietary fatty acid, linoleic acid, and a thiazolidinedione, rosiglitazone, on biochemical and functional aspects of human preadipocyte differentiation in vitro. MATERIALS AND METHODS: Human omental and subcutaneous preadipocytes were subcultured 2-3 times and subsequently differentiated for 21 days in the presence of either linoleic acid or rosiglitazone. Differentiation was assessed using a number of biochemical and functional parameters. RESULTS: Omental and subcutaneous preadipocytes differentiated in the presence of linoleic acid showed marked cytoplasmic triacylglycerol accumulation however, no biochemical markers of differentiation (LPL expression, G3PDH gene expression and enzyme activity and leptin expression or secretion) were detected. In contrast, treatment of these cells with rosiglitazone induced full biochemical differentiation as judged by all markers assessed, despite comparatively little lipid accumulation. The rosiglitazone effects were subcutaneous depot-specific. Cells treated with linoleic acid showed decreased glucose uptake cf rosiglitazone-treated cells. A luciferase reporter assay demonstrated that rosiglitazone potently activates h-peroxisome proliferator activated receptor gamma while linoleic acid had no effect. CONCLUSIONS: These studies demonstrate that (a) human preadipocytes have the potential to accumulate triacylglycerol irrespective of their stage of biochemical differentiation; (b) while omental preadipocytes are refractory to biochemical differentiation in vitro, they are able to accumulate triacylglycerol; and (c) rosiglitazone and linoleic acid may exert their effects via different biochemical pathways.
Authors:
L J Hutley; F M Newell; J M Joyner; S J Suchting; A C Herington; D P Cameron; J B Prins
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of clinical investigation     Volume:  33     ISSN:  0014-2972     ISO Abbreviation:  Eur. J. Clin. Invest.     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-06-19     Completed Date:  2003-09-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0245331     Medline TA:  Eur J Clin Invest     Country:  England    
Other Details:
Languages:  eng     Pagination:  574-81     Citation Subset:  IM    
Affiliation:
Department of Diabetes and Endocrinology, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Queensland, Australia 4102.
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MeSH Terms
Descriptor/Qualifier:
Adipocytes / cytology*,  drug effects
Adipose Tissue / cytology*,  drug effects
Adult
Aged
Cell Differentiation / drug effects*,  physiology
Female
Humans
Hypoglycemic Agents / therapeutic use
Linoleic Acid / therapeutic use*
Male
Middle Aged
Receptors, Cytoplasmic and Nuclear / metabolism
Thiazoles / therapeutic use*
Thiazolidinediones*
Transcription Factors / antagonists & inhibitors,  metabolism
Chemical
Reg. No./Substance:
0/Hypoglycemic Agents; 0/Receptors, Cytoplasmic and Nuclear; 0/Thiazoles; 0/Thiazolidinediones; 0/Transcription Factors; 122320-73-4/rosiglitazone; 2197-37-7/Linoleic Acid

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