Effects of rosiglitazone and linoleic acid on human preadipocyte differentiation.
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.


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.
Hutley
L J
LJ
Department of Diabetes and Endocrinology, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Queensland, Australia 4102.
Newell
F M
FM
Joyner
J M
JM
Suchting
S J
SJ
Herington
A C
AC
Cameron
D P
DP
Prins
J B
JB
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects; D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D019787:Linoleic Acid / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000077154:Rosiglitazone; D013844:Thiazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism
D007004:Hypoglycemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D019787:Linoleic Acid