Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes

Wendy M. Mueller, Francine M. Gregoire, Kimber Stanhope, Charles V. Mobbs, Tooru M. Mizuno, Craig H Warden, Judith S. Stern, Peter J Havel

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Abstract

Circulating leptin secreted from adipocytes is correlated with fat mass and plasma insulin concentrations in humans and rodents. Plasma leptin, insulin, and glucose decrease during fasting and increase after refeeding; however, the underlying mechanisms regulating the changes of leptin secretion are not known. To investigate the role of insulin-stimulated glucose metabolism in the regulation of leptin secretion, we examined the effects of insulin and inhibitors of glucose transport and metabolism on leptin secretion from rat adipocytes in primary culture. Insulin (0.16-16 nM) increased leptin secretion over 96 h; however, the increase in leptin was more closely related to the amount of glucose taken up by the adipocytes (r = 0.64; P < 0.0001) than to the insulin concentration per se (r = 0.20; P < 0.28), suggesting a role for glucose transport and/or metabolism in regulating leptin secretion. 2-Deoxy-D-glucose (2-DG), a competitive inhibitor of glucose transport and phosphorylation, caused a concentration- dependent (2-50 mg/dl) inhibition of leptin release in the presence of 1.6 nM insulin. The inhibitory effect of 2-DG was reversed by high concentrations of glucose. Two other inhibitors of glucose transport, phloretin (0.05-0.25 mM) and cytochalasin-B (0.5-50 μM), also inhibited leptin secretion. Inhibition of leptin secretion by these agents was proportional to the inhibition of glucose uptake (r = 0.60 to 0.86; all P < 0.01). Two inhibitors of glycolysis, iodoacetate (0.005-1.0 mM) and sodium fluoride (0.1-5 mM), produced concentration-dependent inhibition of leptin secretion in the presence of 1.6 nM insulin. In addition, both 2-DG and sodium fluoride markedly decreased the leptin (ob) messenger RNA content of cultured adipocytes, but did not affect 18S ribosomal RNA content. We conclude that glucose transport and metabolism are important factors in the regulation of leptin expression and secretion and that the effect of insulin to increase adipocyte glucose utilization is likely to contribute to insulin-stimulated leptin secretion. Thus, in vivo, decreased adipose glucose metabolism may be one mechanism by which fasting decreases circulating leptin, whereas increased adipose glucose metabolism would increase leptin after refeeding.

Original languageEnglish (US)
Pages (from-to)551-558
Number of pages8
JournalEndocrinology
Volume139
Issue number2
DOIs
StatePublished - 1998

Fingerprint

Leptin
Adipocytes
Glucose
Insulin
Deoxyglucose
Sodium Fluoride
Fasting
18S Ribosomal RNA
Phloretin
Iodoacetates
Cytochalasin B
Glycolysis

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes. / Mueller, Wendy M.; Gregoire, Francine M.; Stanhope, Kimber; Mobbs, Charles V.; Mizuno, Tooru M.; Warden, Craig H; Stern, Judith S.; Havel, Peter J.

In: Endocrinology, Vol. 139, No. 2, 1998, p. 551-558.

Research output: Contribution to journalArticle

Mueller, WM, Gregoire, FM, Stanhope, K, Mobbs, CV, Mizuno, TM, Warden, CH, Stern, JS & Havel, PJ 1998, 'Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes', Endocrinology, vol. 139, no. 2, pp. 551-558. https://doi.org/10.1210/en.139.2.551
Mueller, Wendy M. ; Gregoire, Francine M. ; Stanhope, Kimber ; Mobbs, Charles V. ; Mizuno, Tooru M. ; Warden, Craig H ; Stern, Judith S. ; Havel, Peter J. / Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes. In: Endocrinology. 1998 ; Vol. 139, No. 2. pp. 551-558.
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AU - Havel, Peter J

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AB - Circulating leptin secreted from adipocytes is correlated with fat mass and plasma insulin concentrations in humans and rodents. Plasma leptin, insulin, and glucose decrease during fasting and increase after refeeding; however, the underlying mechanisms regulating the changes of leptin secretion are not known. To investigate the role of insulin-stimulated glucose metabolism in the regulation of leptin secretion, we examined the effects of insulin and inhibitors of glucose transport and metabolism on leptin secretion from rat adipocytes in primary culture. Insulin (0.16-16 nM) increased leptin secretion over 96 h; however, the increase in leptin was more closely related to the amount of glucose taken up by the adipocytes (r = 0.64; P < 0.0001) than to the insulin concentration per se (r = 0.20; P < 0.28), suggesting a role for glucose transport and/or metabolism in regulating leptin secretion. 2-Deoxy-D-glucose (2-DG), a competitive inhibitor of glucose transport and phosphorylation, caused a concentration- dependent (2-50 mg/dl) inhibition of leptin release in the presence of 1.6 nM insulin. The inhibitory effect of 2-DG was reversed by high concentrations of glucose. Two other inhibitors of glucose transport, phloretin (0.05-0.25 mM) and cytochalasin-B (0.5-50 μM), also inhibited leptin secretion. Inhibition of leptin secretion by these agents was proportional to the inhibition of glucose uptake (r = 0.60 to 0.86; all P < 0.01). Two inhibitors of glycolysis, iodoacetate (0.005-1.0 mM) and sodium fluoride (0.1-5 mM), produced concentration-dependent inhibition of leptin secretion in the presence of 1.6 nM insulin. In addition, both 2-DG and sodium fluoride markedly decreased the leptin (ob) messenger RNA content of cultured adipocytes, but did not affect 18S ribosomal RNA content. We conclude that glucose transport and metabolism are important factors in the regulation of leptin expression and secretion and that the effect of insulin to increase adipocyte glucose utilization is likely to contribute to insulin-stimulated leptin secretion. Thus, in vivo, decreased adipose glucose metabolism may be one mechanism by which fasting decreases circulating leptin, whereas increased adipose glucose metabolism would increase leptin after refeeding.

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