Human leptin levels are pulsatile and inversely related to pituitary–ardenal function

Abstract

Leptin communicates nutritional status to regulatory centers in the brain. Because peripheral leptin influences the activity of the highly pulsatile adrenal and gonadal axes, we sought to determine whether leptin levels in the blood are pulsatile. We measured circulating leptin levels every 7 minutes for 24 hours, in six healthy men, and found that total circulating leptin levels exhibited a pattern indicative of pulsatile release, with 32.0 +/- 1.5 pulses every 24 hours and a pulse duration of 32.8 +/- 1.6 minutes. We also show an inverse relation between rapid fluctuations in plasma levels of leptin and those of adrenocorticotropic hormone (ACTH) and cortisol that could not be accounted for on the basis of glucocorticoid suppression of leptin. As leptin levels are pulsatile, we propose that a key function of the CNS is regulated by a peripheral pulsatile signal. In a separate pilot study we compared leptin pulsatility in 414 plasma samples collected every 7 minutes for 24 hours from one obese woman and one normal-weight woman. We found that high leptin levels in the obese subject were due solely to increased leptin pulse height; all concentration-independent pulsatility parameters were almost identical in the two women. Leptin pulsatility therefore can be preserved in the obese.

The leptin hypothesis of depression: a potential link between mood disorders and obesity?

“…Chronic leptin administration can reverse the hypercorticosteronemia in ob/ob mice prior to significant weight loss [44], suggesting a role of leptin in HPA function independent of its effects on energy homeostasis. An interaction between leptin and the HPA axis is further supported by the inverse relation of circadian rhythmicity between plasma leptin and glucocorticoids [45]. Consistent with these data, leptin treatment diminishes the secretion of ACTH and corticosterone in response to stressful events.…”

Clinical implications of leptin and its potential humoral regulators in long-term low-calorie diet therapy for obese humans

“…Falling plasma leptin was shown to be a critical signal that initiates the neuroendocrine response to dietary energy reduction (Ahima et al, 1997). For example, an inverse relationship between plasma leptin levels and the activity of the hypothalamic -pituitary -adrenal axis was reported (Licinio et al, 1997;Spinedi & Gaillard, 1998), suggesting that leptin is not only an adipostatic hormone but also a stress-related factor potentially crucial for survival (Bornstein, 1997;Yanovski, 1997). Taken together, it is probable that a substantial fall in plasma leptin levels during an LCD serves as an adaptation to reduced calorie intake.…”

Reply

“…Previous studies have revealed that some diseases, such as chronic liver diseases, major depression, cardiovascular disease, diabetes mellitus, hypertension, Helicobacter pylori infection, and several inflammatory diseases (such as rheumatoid arthritis and systemic lupus erythematosus) could affect serum leptin levels (3,4). The authors did not mention the above diseases, and this omission could have influenced the findings of the study.…”