Dynamics of Fat Cell Turnover in Humans

Abstract

In most countries today, obesity is increasing at an almost epidemic rate and creating a considerable public health problem by elevating the risk of cardiovascular disease and metabolic disorders such as type 2 diabetes. It is possible that, as a result, life expectancy will begin to decline in developed countries; this would be the first such occurrence in recent history. Factors that influence fat mass in adulthood remain incompletely understood, but increased lipid storage in predeveloped fat cells, or adipocytes, is accepted as a major determinant of fat mass in adults. The number of fat cells is constant in both lean and obese adults, even after marked weight loss, suggesting that the number of adipocytes is set in childhood and the adolescent years. It has not been established, however, whether or not the number of adipocytes changes in adulthood. To clarify the dynamics of the seemingly stable population of adipocytes in adults, the investigators measured adipocyte turnover by analyzing the integration of 14 C derived from nuclear bomb tests into genomic DNA. Approximately 10% of fat cells were found to renew themselves each year at all adult ages, independently of the body mass index. Early-onset obesity does not alter either adipocyte death nor the adipocyte generation rate. This suggests tight regulation of the number of fat cells in adults with this disorder. The relatively high turnover of adipocytes in early-onset obesity may provide a new target for its pharmacological management. The key will be to understand, at a molecular level, the feedback mechanisms that control adipocyte turnover.