Responses of leptin to short-term fasting and refeeding in humans: A link with ketogenesis but not ketones themselves

Jerzy W. Kolaczynski, Robert V. Considine, Joanna Ohannesian, Cheryl Marco, Irina Opentanova, Mark R. Nyce, Michael Myint, José F. Caro

Research output: Contribution to journalArticlepeer-review

457 Scopus citations


We investigated the response of leptin to short-term fasting and refeeding in humans. A mild decline in subcutaneous adipocyte ob gene mRNA and a marked fall in serum leptin were observed after 36 and 60 h of fasting. The dynamics of the leptin decline and rise were further substantiated in a 6-day study consisting of a 36-h baseline period, followed by 36-h fast, and a subsequent refeeding with normal diet. Leptin began a steady decline from the baseline values after 12 h of fasting, reaching a nadir at 36 h. The subsequent restoration of normal food intake was associated with a prompt leptin rise and a return to baseline values 24 h later. When responses of leptin to fasting and refeeding were compared with that of glucose, insulin, fatty acids, and ketones, a reverse relationship between leptin and β-OH- butyrate was found. Consequently, we tested whether the reciprocal responses represented a causal relationship between leptin and β-OH-butyrate. Small amounts of infused glucose equal to the estimated contribution of gluconeogenesis, which was sufficient to prevent rise in ketogenesis, also prevented a fall in leptin. The infusion of β-OH-butyrate to produce hyperketonemia of the same magnitude as after a 36-h fast had no effect on leptin. The study indicates that one of the adaptive physiological responses to fasting is a fall in serum leptin. Although the mediator that brings about this effect remains unknown, it appears to be neither insulin nor ketones.

Original languageEnglish (US)
Pages (from-to)1511-1515
Number of pages5
Issue number11
StatePublished - 1996

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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