RESPONSES OF LEPTIN TO SHORT-TERM FASTING AND REFEEDING IN HUMANS - ALINK WITH KETOGENESIS BUT NOT KETONES THEMSELVES

We investigated the response of leptin to short-term fasting and refee ding 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 f asting. The dynamics of the leptin decline and rise were further subst antiated in a 6-day study consisting of a 36-h baseline period, follow ed by 36-h fast, and a subsequent refeeding with normal diet. Leptin b egan a steady decline from the baseline values after 12 h of fasting, reaching a nadir at 36 h. The subsequent restoration of normal food in take 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 beta-OH-butyrate was found. Consequently, we tested whether the reciprocal responses represented a causal relationship between leptin and beta-OH-butyrate. Small amoun ts of infused glucose equal to the estimated contribution of gluconeog enesis, which was sufficient to prevent rise in ketogenesis, also prev ented a fall in leptin. The infusion of beta-OH-butyrate to produce hy perketonemia 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 neithe r insulin nor ketones.