Decreased serum leptin levels during prolonged high altitude exposure

Abstract

Circulating leptin concentrations are shown to be influenced not only by hormones, but also by body weight and energy balance. High altitude (HA) exposure induces a daily negative energy balance and stress hormone activation. The aim of our study was to evaluate leptin concentration during both acute and prolonged HA exposure and its correlations with some metabolic and hormonal parameters. Twelve males were studied during a stay at HA (15-20 days at 5,050 m). Blood samples for serum leptin, plasma insulin and 24-h urinary epinephrine (E) and norepinephrine (NE) were collected at sea level (SL), at the arrival at HA (A) and after 12-16 days (C) of stay. Symptoms of Acute Mountain Sickness (AMS) were evaluated using the Lake Louise score and the results showed there was no relationship with leptin concentrations. During the stay, both body mass index and leptin levels significantly decreased in both groups [leptin from 1.88 (1.12) to 1.21 (1.04) ng/ml, P<0.008, in A; and to 1.06 (0.74) ng/ml, P<0.003, in C]. Acute HA exposure induced a clear-cut significant increase of NE ( P<0.001 in A, P<0.003 in C) while E and insulin levels were unchanged in both phases. Moreover, a significant correlation between leptin and NE absolute values, and leptin and insulin variations was found ( r 0.359, P<0.034 and r=0.560, P<0.007, respectively). Exposure to HA induces a decrease in fasting serum leptin concentrations in men. These changes are not linked to symptoms of AMS but to hormonal and energy balance variations, suggesting that leptin is involved in the endocrine and metabolic adaptations occurring during HA exposure.

Endocrine and metabolic responses to extreme altitude and physical exercise in climbers

“…An increase in leptin coupled with ghrelin decrease has been described after acute exposure to HA (17,19), but other authors reported that prolonged HA exposure is associated with a reduction of leptin concentrations, likely due to the loss of body mass and the strong hypoxia-related sympathetic activation (18). These studies relied on single leptin and ghrelin measurements while we evaluated mean leptin and ghrelin concentrations over 2 h. Indeed, we found a nonsignificant trend toward decreased leptin levels, but ghrelin levels were completely unchanged despite the significant body weight loss.…”

“…More recently, the emerging role of leptin and ghrelin in the regulation of energy balance prompted an evaluation of leptin response to HA (17)(18)(19)(20). Subjects exposed to HA lose significant amounts of body mass from fat mass as well as fat-free mass, particularly if involved in physical performance such as climbing (10,11).…”

“…In this context, significant variations in leptin and ghrelin secretion were expected but the data available so far are discrepant. Leptin levels have been reported as either increased (17,19), decreased (18), or unchanged (20), while a trend towards decreased ghrelin levels has been reported at HA (19).…”

Adaptation of ghrelin and the GH/IGF axis to high altitude

“…However, hypoxia has been shown to clearly increase leptin gene expression in adipocyte studies (40). As suggested by Zaccaria et al (38), it therefore seems plausible that exposure to HA leads to a leptin increase, which causes a satiety signal to the brain contributing to anorexia and weight loss.…”

“…Published data have been somewhat inconsistent reporting an increase (12,37), a decrease (38), or no change (13,39) in leptin after ascent to HA. However, hypoxia has been shown to clearly increase leptin gene expression in adipocyte studies (40).…”