FatCellTurnover - Vol 453 | 5 June 2008 |...

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LETTERS Dynamics of fat cell turnover in humans Kirsty L. Spalding 1 , Erik Arner 1 ,Pa ˚l O. Westermark 2 , Samuel Bernard 3 , Bruce A. Buchholz 4 , Olaf Bergmann 1 , Lennart Blomqvist 5 , Johan Hoffstedt 5 , Erik Na ¨slund 6 , Tom Britton 7 , Hernan Concha 5 , Moustapha Hassan 5 , Mikael Ryde ´n 5 , Jonas Frise ´n 1 5 Obesity is increasing in an epidemic manner in most countries and constitutes a public health problem by enhancing the risk for cardiovascular disease and metabolic disorders such as type 2 dia- betes 1,2 . Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history 3 . The factors determining fat mass in adult humans are not fully understood, but increased lipid storage in already developed fat cells (adipocytes) is thought to be most important 4,5 . Here we show that adipocyte number is a major determinant for the fat mass in adults. However, the number of fat cells stays constant in adulthood in lean and obese individuals, even after marked weight loss, indicating that the number of adipocytes is set during childhood and adolescence. To establish the dynamics within the stable population of adipocytes in adults, we have measured adipocyte turnover by analysing the integration of 14 C derived from nuclear bomb tests in genomic DNA 6 . Approximately 10% of fat cells are renewed annually at all adult ages and levels of body mass index. Neither adipocyte death nor generation rate is altered in early onset obesity, suggesting a tight regulation of fat cell number in this condition during adulthood. The high turnover of adipocytes establishes a new therapeutic target for pharmacological intervention in obesity. The fat mass can expand by increasing the average fat cell volume and/or the number of adipocytes. Increased fat storage in fully dif- ferentiated adipocytes, resulting in enlarged fat cells, is well docu- mented and is thought to be the most important mechanism whereby fat depots increase in adults 4,5 . To analyse the contribution of the fat cell volume in adipocytes to the size of the fat mass, we first analysed the relationship between fat cell volume and total body fat mass (directly measured with bioimpedance or estimated from body mass index (BMI), sex and age in a large cohort of adults). As expected, there was a positive correlation between the measures of fat mass and fat cell volume both in subcutaneous fat (Fig. 1a–c), which represents about 80% of all fat, and in visceral fat (Fig. 1d), which has a strong link to metabolic complications of obesity. However, the relationship between fat cell volume and fat mass markedly differed from a linear relationship (likelihood ratio test P , 0.001, and Akaike information criterion, described in Supplementary Information 1) in both sub- cutaneous and visceral adipose regions and both sexes, indicating that fat mass is determined by both adipocyte number and size. In the nonlinear case, both fat cell number and fat cell size determine fat
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This note was uploaded on 03/01/2010 for the course NPB 97952 taught by Professor ? during the Fall '09 term at UC Davis.

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FatCellTurnover - Vol 453 | 5 June 2008 |...

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