Glucose availability controls adipogenesis in mouse 3T3-L1 adipocytes via up-regulation of nicotinamide metabolism.
Expansion of adipose tissue in response to a positive energy balance underlies obesity and occurs through both hypertrophy of existing cells and increased differentiation of adipocyte precursors (hyperplasia). To better understand the nutrient signals that promote adipocyte differentiation, we investigated the role of glucose availability in regulating adipocyte differentiation and maturation. 3T3-L1 preadipocytes were grown and differentiated in medium containing a standard differentiation hormone mixture and either 4 or 25 mm glucose. Adipocyte maturation at day 9 post-differentiation was determined by key adipocyte markers, including glucose transporter 4 (GLUT4) and adiponectin expression and Oil Red O staining of neutral lipids. We found that adipocyte differentiation and maturation required a pulse of 25 mm glucose only during the first 3 days of differentiation. Importantly, fatty acids were unable to substitute for the 25 mm glucose pulse during this period. The 25 mm glucose pulse increased adiponectin and GLUT4 expression and accumulation of neutral lipids via distinct mechanisms. Adiponectin expression and other early markers of differentiation required an increase in the intracellular pool of total NAD/P. In contrast, GLUT4 protein expression was only partially restored by increased NAD/P levels. Furthermore, GLUT4 mRNA expression was mediated by glucose-dependent activation of GLUT4 gene transcription through the cis-acting GLUT4-liver X receptor element (LXRE) promoter element. In summary, this study supports the conclusion that high glucose promotes adipocyte differentiation via distinct metabolic pathways and independently of fatty acids. This may partly explain the mechanism underlying adipocyte hyperplasia that occurs much later than adipocyte hypertrophy in the development of obesity.
['Jackson|Robert M|RM|', 'Griesel|Beth A|BA|', 'Gurley|Jami M|JM|', 'Szweda|Luke I|LI|', 'Olson|Ann Louise|AL|']
D041721:3T3-L1 Cells D052438:Adipocytes, White D050156:Adipogenesis D052242:Adiponectin D052436:Adipose Tissue, White D000818:Animals D015415:Biomarkers D002478:Cells, Cultured D005786:Gene Expression Regulation D005947:Glucose D051275:Glucose Transporter Type 4 D006943:Hyperglycemia D007003:Hypoglycemia D050155:Lipogenesis D000071518:Liver X Receptors D051379:Mice D008810:Mice, Inbred C57BL D009243:NAD D009249:NADP D011401:Promoter Regions, Genetic D017154:Stromal Cells D015854:Up-Regulation
adipocyte differentiation adiponectin NAD glucose metabolism glucose transporter type 4 (GLUT4) lipogenesis