Effects of rosiglitazone and linoleic acid on human preadipocyte differentiation

Hutley, L. J., Newell, F. M., Joyner, J. M., Suchting, S. J., Herington, A. C., Cameron, D. P. and Prins, J. B. (2003) Effects of rosiglitazone and linoleic acid on human preadipocyte differentiation. European Journal of Clinical Investigation, 33 7: 574-581. doi:10.1046/j.1365-2362.2003.01178.x


Author Hutley, L. J.
Newell, F. M.
Joyner, J. M.
Suchting, S. J.
Herington, A. C.
Cameron, D. P.
Prins, J. B.
Title Effects of rosiglitazone and linoleic acid on human preadipocyte differentiation
Journal name European Journal of Clinical Investigation   Check publisher's open access policy
ISSN 0014-2972
1365-2362
Publication date 2003-07
Sub-type Article (original research)
DOI 10.1046/j.1365-2362.2003.01178.x
Volume 33
Issue 7
Start page 574
End page 581
Total pages 8
Editor J. J. M. Marx
Place of publication United Kingdom
Publisher Blackwell Publishing Ltd
Collection year 2003
Language eng
Subject C1
321004 Endocrinology
730105 Endocrine organs and diseases (incl. diabetes)
Abstract 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.
Keyword Medicine, Research & Experimental
Adipose Tissue
Human
Linoleic Acid
Preadipocyte Differentiation
Rosiglitazone
Activated Receptor-gamma
Adipose-tissue
Gene-expression
Adipocyte Differentiation
Ppar-gamma
3t3-l1 Adipocytes
Oxidative Stress
Glucose-uptake
Body-weight
Medicine, General & Internal
Fatty-acids
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 01:28:24 EST