Spalding Kirsty L, Arner Erik, Westermark Pål O, Bernard Samuel, Buchholz Bruce A, Bergmann Olaf, Blomqvist Lennart, Hoffstedt Johan, Näslund Erik, Britton Tom, Concha Hernan, Hassan Moustapha, Rydén Mikael, Frisén Jonas, Arner Peter
Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
Nature. 2008 Jun 5;453(7196):783-7. doi: 10.1038/nature06902. Epub 2008 May 4.
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.
在大多数国家，肥胖正以流行的方式增加，并通过增加心血管疾病和代谢紊乱（如2型糖尿病）的风险构成一个公共卫生问题。由于肥胖的增加，发达国家的预期寿命可能在近代史上首次开始下降。决定成年人体脂肪量的因素尚未完全了解，但已发育的脂肪细胞（脂肪细胞）中脂质储存的增加被认为是最重要的。在这里，我们表明脂肪细胞数量是成年人脂肪量的主要决定因素。然而，无论是瘦人还是肥胖者，成年后脂肪细胞的数量都保持不变，即使在显著体重减轻后也是如此，这表明脂肪细胞的数量在儿童期和青春期就已确定。为了确定成年人中稳定的脂肪细胞群体的动态变化，我们通过分析基因组DNA中来自核弹试验的14C的整合来测量脂肪细胞的更新率。在所有成年年龄和体重指数水平下，每年约有10%的脂肪细胞更新。早发性肥胖患者的脂肪细胞死亡和生成率均未改变，这表明成年期这种情况下脂肪细胞数量受到严格调控。脂肪细胞的高更新率为肥胖的药物干预建立了一个新的治疗靶点。
