Article

Dynamics of fat cell turnover in humans. Nature 453, 783-787

Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
Nature (Impact Factor: 42.35). 07/2008; 453(7196):783-7. DOI: 10.1038/nature06902
Source: PubMed

ABSTRACT 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 diabetes. Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history. 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. 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 14C derived from nuclear bomb tests in genomic DNA. 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.

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    • "The rate of this process is intermediate between epithelial cells and myocytes. In young adult mice, ?10%–15% of adipocytes are replaced every month (Rigamonti et al., 2011; Tang et al., 2011), and retrospective human studies also indicate a high turnover rate (Spalding et al., 2008). Under homeostatic conditions, the process is relatively constant, but it is sensitive to pharmacologic, physiologic, and dietary stimuli. "
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    • "Adipose-derived hormones and cytokines directly modulate systemic insulin sensitivity (Qatanani and Lazar, 2007). WAT expands by an increase in adipocyte number (hyperplasia ) and size (hypertrophy) (Spalding et al., 2008; Tchoukalova et al., 2010). Adipocytes derive from mesenchymal stem cells (MSCs) and preadipocytes that reside in the stromovascular fraction of WAT. "
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    • "In isolated adipocytes, we do not find significant fat depotrelated differences in TL supporting the notion that the number of adipocytes remains largely constant during adulthood [6]. Higher preadipocyte proliferation rate in SAT compared to VAT may not be reflected by different TL in mature adipocytes due to the relatively low renewal rate of adipocytes [6]. One limitation of our study is that we can only evaluate TL at a given time point and can therefore not exclude that differences in the dynamic of adipocyte turn over exist between different fat depots. "
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