Lönnqvist F, Nordfors L, Jansson M, Thörne A, Schalling M, Arner P
Department of Medicine and Research Center, Huddinge Hospital, Karolinska Institute, S-141 86 Stockholm, Sweden.
J Clin Invest. 1997 May 15;99(10):2398-404. doi: 10.1172/JCI119422.
The role of expression and secretion of the ob gene product, leptin, for the regulation of plasma leptin levels has been investigated in vitro using abdominal subcutaneous adipose tissue of 20 obese, otherwise healthy, and 11 nonobese women. Body mass index (BMI, mean+/-SEM; kg/m2) in the two groups was 41+/-2 and 23+/-1, respectively. Fat cell volume was 815+/-55 pl in the obese and 320+/-46 pl in the nonobese group. In the obese group, plasma leptin concentrations and adipose leptin mRNA (relative to gamma actin) were increased five and two times, respectively. Moreover, adipose tissue secretion rates per gram lipid weight or per fat cell number were also increased two and seven times, respectively, in the obese group. There were strong linear correlations (r = 0.6-0.8) between plasma leptin, leptin secretion, and leptin mRNA. All of these leptin measurements correlated strongly with BMI and fat cell volume (r = 0.7- 0.9). About 60% of the variation in plasma leptin could be attributed to variations in leptin secretion rate, BMI, or fat cell volume. We conclude that elevated circulating levels of leptin in obese women above all result from accelerated secretion rates of the peptide from adipose tissue because of increased ob gene expression. However, leptin mRNA, leptin secretion, and circulating leptin levels are all more closely related to the stored amount of lipids in the fat cells of adipose tissue than they are to an arbitrary division into obese versus nonobese.
利用20名肥胖但健康的女性和11名非肥胖女性的腹部皮下脂肪组织,在体外研究了肥胖基因产物瘦素的表达和分泌对血浆瘦素水平的调节作用。两组的体重指数(BMI,均值±标准误;kg/m²)分别为41±2和23±1。肥胖组脂肪细胞体积为815±55皮升,非肥胖组为320±46皮升。在肥胖组中,血浆瘦素浓度和脂肪组织瘦素mRNA(相对于γ肌动蛋白)分别增加了5倍和2倍。此外,肥胖组每克脂质重量或每个脂肪细胞的脂肪组织分泌率也分别增加了2倍和7倍。血浆瘦素、瘦素分泌和瘦素mRNA之间存在强线性相关性(r = 0.6 - 0.8)。所有这些瘦素测量值均与BMI和脂肪细胞体积密切相关(r = 0.7 - 0.9)。血浆瘦素约60%的变异可归因于瘦素分泌率、BMI或脂肪细胞体积的变异。我们得出结论,肥胖女性循环中瘦素水平升高首先是由于肥胖基因表达增加导致脂肪组织中该肽分泌率加快所致。然而,瘦素mRNA、瘦素分泌和循环瘦素水平与脂肪组织脂肪细胞中脂质储存量的关系比与简单分为肥胖与非肥胖的关系更为密切。