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1 Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
* To whom correspondence should be addressed. E-mail: yy102{at}columbia.edu.
The growth and aging of 3T3-L1 adipocytes was investigated in a synchronized tissue-culture system. We systematically characterized several major aspects of adipocyte metabolism and functions as variables of cell-age. We found that terminal differentiation of 3T3-L1 cells is followed by a near-linear hypertrophic growth (increase in TG content) of the cultured adipocytes throughout a 20-day study period. However, three metabolically and functionally distinct stages are recognized. The first stage overlaps with differentiation and is represented by small immature adipocytes. The second stage is characterized by fully mature adipocytes that show peaked overall metabolic activities. The third stage is marked by cell aging with deterioration in every major aspect of the cell's functionality, except for the function of net energy-storage, which is preserved even in aged adipocytes. Compared with young mature adipocytes, older cells are increasingly insulin resistant, have decreased glucose uptake and fuel consumption, and show impaired glycerokinase-mediated fatty acid re-esterification. Moreover, aged adipocytes show reduced gene expression for adiponectin and leptin, each of which is important in systemic regulation of energy metabolism. The characterization of these cell age-dependent changes in adipocyte functionality provides a model for understanding dynamic changes at the tissue level, and suggests that adipose tissue is modifiable via adipocyte aging.
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