Hexosamines regulate leptin production in human subcutaneous adipocytes

Robert V. Considine, Robert C. Cooksey, Lloyd B. Williams, Rachael L. Fawcett, Peili Zhang, Walter T. Ambrosius, Robert M. Whitfield, Rosemarie Jones, Margaret Inman, John Huse, Donald A. McClain

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

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 2-fold in the sc adipose tissue of 17 obese [body mass index (BMI), 41.3 ± 12.0 kg/m2; age, 31 ± 5 yr] subjects compared to 14 lean (BMI, 23.4 ± 1.6 kg/m2; age, 33 ± 11 yr) 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/m2; n = 6) and obese (BMI, 55.4 ± 13.0 kg/m2; 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 h of treatment. These findings suggest that hexosamine biosynthesis regulates leptin production in human adipose tissue.

Original languageEnglish (US)
Pages (from-to)3551-3556
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume85
Issue number10
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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