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Adipogenesis plays an important role in metabolic homeostasis and nutrient pathways, and is crucial for regulating body fat reserves and body weight of mammals.The transcriptional control of adipogenesis requires a sequential series of gene expression events and activation of a number of key signaling pathways.Abundant energy supply in the diet is a primary driver of adipogenesis.To investigate the function of extracellular nutrient molecules (1, 25-dihydroxyvitamin D (1, 25-(OH)2D3) and retinoic acid (RA)) in regulation of adipogenesis, adipocyte differentiation and key adipogenic gene expression were studied in 3T3-L1preadipocytes.Lipid accumulation was measured by Oil Red O staining and expression of key adipogenic genes was quantified using quantitative real-time PCR.Adipogenic responses to different concentrations of 1,25-(OH)2D3 or RA were determined on day 2, 4, 6, 8, 10 after induction of adipogenesis with the traditional hormonal cocktail (dexamethasone, isobutyl-1-methylxanthine and insulin) in the absence or presence of 1,25-(OH)2D3 or RA.In response to high concentrations (10-7, 10-s, 10-9 M) of 1, 25-(OH)2D3, lipid accumulation and the expression of PPARγ, C~BPα, FABP4 and SCD-1 were inhibited through day 10.In response to high concentration (10-6, 10-7 M) of RA, lipid accumulation and the expression of PPARγ, C/EBPα, FABP4 and SCD-1 were inhibited through day 8, but on day 10, lipid accumulation and the expression levels of these genes rebounded to levels comparable to the control.Interestingly, the greatest effects of 1, 25-(OH)2D3 and RA treatments were upon expression of FABP4.However, expression of SREBP-1c was not affected.The lowest concentrations of 1, 25-(OH)2D3 or RA tested did not affect adipocyte differentiation or expression of adipogenic genes.These results indicate that 1, 25-(OH)2D3 and RA inhibited adipogenesis via suppressing adipogenic specific genes, especially FABP4.Our data suggest that a deeper understanding of the roles of these nutrient factors in regulating adipogenesis will be informed by further studies of adipogenic specific gene promoter activity.