Liver X receptor preferentially activates de novo lipogenesis in human preadipocytes.
The liver X receptor (LXR) was demonstrated to play a key role in cholesterol metabolism in liver, intestine and macrophage. However, its function on the regulation of preadipocyte differentiation remains unclear since contradictory results were reported. The objective of the present study was to unravel the functionality of LXR in human preadipocytes. We show that the LXR agonist T0901317 strongly stimulated the expression of SREBP-1c and the lipogenic enzymes ACC-1, FAS and SCD-1 in both the human preadipose cell line Chub-S7 as well as human primary stromal vascular fraction (SVF) cells. The effects on gene expression were associated with the stimulation of de novo lipogenesis in both cell models, resulting in the induction of lipid accumulation. In contrast with a PPARgamma agonist (BRL49653), T0901317 enhanced only slightly the expression of PPARgamma dependent genes (PPARgamma, aP2 and adiponectin) in Chub-S7 cells and failed to change their expression in human SVF cells. These results show that LXR stimulated preferentially triglyceride accumulation in human preadipocytes via the induction of de novo lipogenesis, rather than activating the differentiation process through PPARgamma activation.
Darimont
Christian
C
Nestlé Research Center, P.O. Box 44, Vers-Chez-Les-Blanc, 1000 Lausanne 26, Switzerland. christian.darimont@rdls.nestle.com
Avanti
Ornella
O
Zbinden
Irène
I
Leone-Vautravers
Patricia
P
Mansourian
Robert
R
Giusti
Vittorio
V
Macé
Katherine
K
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D015415:Biomarkers; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D050155:Lipogenesis; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis / Q000378:metabolism
D015415:Biomarkers; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides