Hexosamines regulate leptin production in human subcutaneous adipocytes

被引:52
作者
Considine, RV
Cooksey, RC
Williams, LB
Fawcett, RL
Zhang, PL
Ambrosius, WT
Whitfield, RM
Jones, R
Inman, M
Huse, J
McClain, DA
机构
[1] Indiana Univ, Sch Med, Div Endocrinol & Metab, Indianapolis, IN 46202 USA
[2] Indiana Univ, Sch Med, Div Biostat, Indianapolis, IN 46202 USA
[3] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA
[4] Indiana Univ, Sch Med, Dept Surg, Indianapolis, IN 46202 USA
[5] St Vincents Hosp, Dept Surg, Carmel, IN 46032 USA
[6] Univ Utah, Sch Med, Div Endocrinol & Metab, Dept Med, Salt Lake City, UT 84132 USA
[7] Vet Affairs Med Ctr, Salt Lake City, UT 84132 USA
关键词
D O I
10.1210/jc.85.10.3551
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The hexosamine biosynthetic pathway has recently been proposed as a mechanism through which cells "sense" nutrient flux to regulate leptin release. This study was undertaken to examine the regulation of leptin production by hexosamines in human adipocytes. Adipose tissue UDP-N-acetylglucosamine, an end product of hexosamine biosynthesis, was elevated 3.2-fold, and ob messenger ribonucleic acid was elevated a-fold in the sc adipose tissue of 17 obese [body mass index (BMI), 41.3 +/- 12.0 kg/m(2); age, 31 +/- 5 yr] subjects compared to 14 lean (BMI, 23.4 +/- 1.6 kg/m(2); age, 33 +/- 11yr) subjects. Serum leptin was increased 2.7-fold in the obese subjects. A significant positive relationship was found between adipose tissue UDP-N-acetylglucosamine and BMI (Spearman correlation = 0.576; P = 0.0007) and between UDP-N-acetylglucosamine and serum leptin (Spearman correlation = 0.4650; P = 0.0145). Treatment of isolated sc adipocytes with 1 mmol/L glucosamine, an intermediate product in UDP-N-acetylglucosamine biosynthesis, increased leptin release 21.4 +/- 17.6% (mean +/- SD) over control (P = 0.0365) and 74.5 +/- 82.8% over control (P = 0.0271) in adipocytes from lean (BMI, 23.2 +/- 1.6 kg/m(2); n = 6) and obese (BMI, 55.4 +/- 13.0 kg/m(2); n = 9) subjects, respectively, by 48 h of culture. Inhibition of UDP-N-acetylglucosamine biosynthesis with 6-diazo-5-oxo-norleucine reduced glucose-stimulated leptin release from cultured adipocytes 21.8 +/- 32.4% (P = 0.0395; n = 12) and ob gene expression 19.9 +/- 18.9% (P = 0.0208; n = 8) by 48 b of treatment. These findings suggest that hexosamine biosynthesis regulates leptin production in human adipose tissue.
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收藏
页码:3551 / 3556
页数:6
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