Evidence that tumor necrosis factor-alpha-induced hyperinsulinemia prevents decreases of circulating leptin during fasting in rats

Edward A. Medica, Kent L Erickson, Kimber Stanhope, Peter J Havel

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Administration of tumor necrosis factor-alpha (TNF-α) acutely increases leptin gene expression and circulating leptin concentrations in rodents and humans. Since TNF-α also induces hyperinsulinemia, and because insulin is a potent stimulator of leptin production, we hypothesized that elevated plasma insulin mediates TNF-α-induced increases of circulating leptin. To test this hypothesis, rats were made insulin-deficient with streptozotocin (STZ) and treated with subcutaneous implants that released insulin at a constant rate and thereby "clamped" insulin levels. STZ-diabetic and nondiabetic rats were injected with TNF-α or vehicle; plasma leptin, insulin, and glucose concentrations were measured during an initial 12-hour postinjection period of fasting and after a subsequent 12-hour period of refeeding. Food intake during the 12 hours after fasting was assessed as a physiologic correlate of changes in leptin concentrations. In nondiabetic rats, TNF-α increased plasma insulin (P = .016) and prevented the fasting-induced decrease of circulating leptin (P = .004) over the initial 12 hours compared with vehicle. Food intake during the refeeding period was 30% lower (P = .008) when the nondiabetic animals were injected with TNF-α. In contrast, TNF-α did not affect leptin concentrations in STZ-diabetic animals with clamped plasma insulin levels or their food intake during the refeeding period. These results suggest that TNF-α-induced hyperinsulinemia likely mediates the stimulatory effect of TNF-α on circulating leptin in vivo. Elevated leptin levels may in turn contribute to the effect of TNF-α to decrease food intake.

Original languageEnglish (US)
Pages (from-to)1104-1110
Number of pages7
JournalMetabolism: Clinical and Experimental
Volume51
Issue number9
DOIs
StatePublished - Sep 2002

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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