Hexosamines regulate leptin production in human subcutaneous adipocytes

Robert 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 journalArticle

55 Citations (Scopus)

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

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Hexosamines
Uridine Diphosphate N-Acetylglucosamine
Leptin
Adipocytes
Uridine Diphosphate
Acetylglucosamine
Biosynthesis
Body Mass Index
Adipose Tissue
Tissue
Diazooxonorleucine
Glucosamine
Biosynthetic Pathways
Serum
Gene expression
Nutrients
RNA
Fluxes
Gene Expression
Glucose

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Considine, R., Cooksey, R. C., Williams, L. B., Fawcett, R. L., Zhang, P., Ambrosius, W. T., ... McClain, D. A. (2000). Hexosamines regulate leptin production in human subcutaneous adipocytes. Journal of Clinical Endocrinology and Metabolism, 85(10), 3551-3556.

Hexosamines regulate leptin production in human subcutaneous adipocytes. / Considine, Robert; Cooksey, Robert C.; Williams, Lloyd B.; Fawcett, Rachael L.; Zhang, Peili; Ambrosius, Walter T.; Whitfield, Robert M.; Jones, Rosemarie; Inman, Margaret; Huse, John; McClain, Donald A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 85, No. 10, 2000, p. 3551-3556.

Research output: Contribution to journalArticle

Considine, R, Cooksey, RC, Williams, LB, Fawcett, RL, Zhang, P, Ambrosius, WT, Whitfield, RM, Jones, R, Inman, M, Huse, J & McClain, DA 2000, 'Hexosamines regulate leptin production in human subcutaneous adipocytes', Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 10, pp. 3551-3556.
Considine R, Cooksey RC, Williams LB, Fawcett RL, Zhang P, Ambrosius WT et al. Hexosamines regulate leptin production in human subcutaneous adipocytes. Journal of Clinical Endocrinology and Metabolism. 2000;85(10):3551-3556.
Considine, Robert ; Cooksey, Robert C. ; Williams, Lloyd B. ; Fawcett, Rachael L. ; Zhang, Peili ; Ambrosius, Walter T. ; Whitfield, Robert M. ; Jones, Rosemarie ; Inman, Margaret ; Huse, John ; McClain, Donald A. / Hexosamines regulate leptin production in human subcutaneous adipocytes. In: Journal of Clinical Endocrinology and Metabolism. 2000 ; Vol. 85, No. 10. pp. 3551-3556.
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