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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