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Chronobiology of Recombinant Leptin Therapy
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To the Editor: Dr Heymsfield and colleagues1 documented the effect of exogenous leptin administration on body weight and showed that only patients in the highest dose groups had significant weight loss compared with those taking placebo. We suggest that the physiological characteristics of leptin may be relevant to its pharmacokinetics.
Diurnal and ultradian oscillations are essential characteristics of hormone secretion. Leptin is characterized by nyctohemeral rhythms, with serum leptin concentrations being highest around midnight.2 This pattern closely resembles the circadian rhythmicity of other hormones, such as thyrotropin and prolactin, and precedes the peak concentrations of cortisol and growth hormone. To what extent the nocturnal increase in leptin is related to biological activity remains to be clarified. In humans, the nocturnal increase in leptin secretion seems to be entrained to meal timing and most likely is related to the cumulative hyperinsulinemia from food ingestion during the entire waking period.
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