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Administration of leptin minimizes the fasting-induced fall in serum thyrotropin, but not triiodothyronine

(July 2003)

The background of the study. Leptin is a product of adipose tissue that decreases appetite and increases energy expenditure. Its production falls during starvation, and this fall may mediate the metabolic and hormonal adaptations that limit the harmful effects of starvation. This study was done to determine the effects of leptin administration during starvation in normal subjects.

How the study was done. Six normal young men were studied while eating a normal diet and during three-day fasts during which they received a low dose of leptin, a higher dose of leptin, or placebo. The higher dose was designed to compensate for the progressive fall in serum leptin concentrations that occurs during fasting. The leptin was injected subcutaneously, four times on days 1 to 3 and once on day 4. Weight, metabolic rate, and serum leptin and other hormones were measured at the start and on day 3 or 4 of each study period. On day 3, serum thyrotropin (TSH) was measured every 15 minutes for 24 hours.

The results of the study. The mean serum leptin concentration decreased from 2.2 to 0.3 ng/ml on day 4 of the fasting study and from 1.9 to 0.5 ng/ml on day 4 of the fasting plus low-dose leptin study; it increased from 3.4 to 7.4 ng/ml on day 4 of the higher-dose leptin study. During all fasting studies the men lost approximately 2 kg, and their resting metabolic rate increased by approximately 250 kcal/day.

The mean serum total and free thyroxine concentrations changed little during any study. The mean serum triiodothyronine concentration decreased by about 30 percent during each fasting study, independent of leptin administration. During day 3 of fasting there was a reduction in mean 24-hour serum TSH concentration, TSH secretion per pulse, and the area under the serum TSH curve; the decreases were partially restored during leptin administration.

The conclusions of the study. The fasting-induced fall in serum TSH concentrations but not the fall in serum triiodothyronine concentrations is blunted by leptin administration.

The original article. Chan JL, Heist K, DePaoli AM, Veldhuis JD, Mantzoros CS. The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. J Clin Invest 2003;111:1409-21.

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Nonthyroidal Illness