leptin and Altitude-Sickness

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.

Topics: Adaptation, Physiological; Adult; Altitude; Altitude Sickness; Homeostasis; Humans; Leptin; Male; Middle Aged; Time Factors

High altitude hypobaric hypoxia environment impairs male's reproductive function. Leptin is an adipose tissue-derived hormone which regulates body weight homeostasis. Its receptor (LepR) has been found in all levels of male reproductive axis, indicating that it can affect male reproductive system in a direct or (and) indirect way. However, the role of leptin signaling in hypobaric hypoxia induced male reproductive dysfunction remains to be elucidated. In this study, we investigated the changes of leptin levels in male SD rats in stimulated altitude of 5500 m hypobaric hypoxia environment and their effects on the hypothalamus-pituitary-gonad axis (HPG axis). A hypoxia animal model was established using a hypobaric hypoxia chamber. Rats were divided randomly into 1, 7, 14, 28-day hypoxia group, recovery group (14 days hypoxia+14 days normoxia) and their control groups. Hypoxia groups displayed obvious changes of testicular and epididymis index compared to control groups. The total number of sperm and sperm motility rate decreased dramatically, while sperm deformity rate increased in hypoxia groups. The flow cytometry analysis showed that the percentage of haploid in 1-day, 7-day and 28-day hypoxia groups increased while the proportion of diploid decreased in 14-day and 28-day hypoxia group. TUNEL staining showed that the testis cells apoptosis index (AI) of hypoxia groups increased significantly, and the apoptosis of cells mainly focus on spermatogonia and spermatocytes. The expression of GnRH in hypothalamus decreased dramatically under hypoxia condition, accompanied with the reduction of serum testosterone (T) level in 1-day and 28-day hypoxia groups and free-testosterone level (FT) in 1-day and 14-day hypoxia groups. Importantly, ELISA analysis showed that serum leptin level decreased in 7-day hypoxia groups and acylated-ghrelin, gastrin also changed, accompanying with reduction of LepR in hypothalamus in hypoxia groups. Immunohistochemical staining exhibited increased leptin and LepR in testis under hypobaric hypoxia conditions. Our results suggested that simulated high altitude hypobaric hypoxia environment decreased male reproductive function, depressed HPG axis activity and altered the serum concentration of hormones related to food intake in adult male rats. Additionally, hypobaric hypoxia induced the leptin-LepR expression in adult male rats' testis, suggesting leptin-LepR signaling may mediate hypoxia-induced impairment in male rats' reproductive

Topics: Altitude; Altitude Sickness; Animals; Apoptosis; Disease Models, Animal; Humans; Hypothalamo-Hypophyseal System; Hypoxia; Leptin; Male; Rats; Rats, Sprague-Dawley; Receptors, Leptin; Reproduction; Sperm Count; Sperm Motility; Spermatogenesis; Testis

Liu, Xiang-Wen, Jie Yin, Qi-Sheng Ma, Chu-Chu Qi, Ji-Ying Mu, Lang Zhang, Li-Ping Gao, and Yu-Hong Jing. Role of arcuate nucleus in the regulation of feeding behavior in the process of altitude acclimatization in rats. High Alt Med Biol. 18:234-241, 2017.-Highly efficient energy utilization and metabolic homeostasis maintenance rely on neuromodulation. Altitude exposure is known to stimulate neuroendocrine systems to respond to acute hypoxia and adaptive acclimatization. However, limited data on how the adaptive regulation of the arcuate nucleus performs in the process of altitude acclimatization are available. In the present study, male Sprague Dawley rats were transported to Huashixia, Qinghai (with an altitude of 4400 m) from Xian (with an altitude of 300 m) by air; rats were consistently raised in Xian as control. Food uptake and body weight were measured consecutively after being subjected to high-altitude condition. Contents of plasma leptin and ghrelin were analyzed by the Enzyme Linked Immunosorbent Assay (ELISA) Kits. Brain coronal sections were obtained, and neuropeptide Y (NPY), proopiomelanocotin (POMC), and c-fos immunoreactivity in arcuate nucleus were observed. Arcuate nucleus was isolated from the hypothalamus, and the mRNA of NPY and POMC were measured by quantitative real-time polymerase chain reaction. Our results showed both food consumption and body weight decreased in the high plateau compared with rats raised in the low-altitude condition. Plasma leptin increased at the early stage, and ghrelin decreased at a later stage after reaching the high plateau. The peak of c-fos immunoreactivity in the arcuate nucleus was at day 3 after reaching the high plateau. The expression level of NPY increased, and POMC decreased in the arcuate nucleus at day 7 after reaching the high plateau compared with the plain control group. These results indicate that the arcuate nucleus of hypothalamus performs an important function in regulating feeding behavior during altitude acclimatization. Our study suggested that altitude acclimation is regulated by the hypothalamus that received leptin and ghrelin signals to response by its microcircuit, including NPY- and POMC-neurons in the arcuate nucleus.

Topics: Acclimatization; Altitude; Altitude Sickness; Animals; Arcuate Nucleus of Hypothalamus; Body Weight; China; Feeding Behavior; Genes, fos; Ghrelin; Hypothalamus; Leptin; Male; Neuropeptide Y; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; RNA, Messenger

Topics: Adult; Altitude; Altitude Sickness; Anorexia; Appetite; Blood Glucose; Humans; Leptin; Longitudinal Studies; Male; Mountaineering; Time Factors

The anorexic effect of exposure to high altitude may be related to the reduction in the arterial oxygen content (Ca(O2)) induced by hypoxemia and possibly the associated decreased convective oxygen transport (COT). This study was then performed to evaluate the effects of either transfusion-induced polycythemia or previous acclimation to hypobaria with endogenously induced polycythemia on the anorexic effect of simulated high altitude (SHA) in adult female rats. Food consumption, expressed in g/d/100 g body weight, was reduced by 40% in rats exposed to 506 mbar for 4 d, as compared to control rats maintained in room air. Transfusion polycythemia, which significantly increased hematocrit, hemoglobin concentration, Ca(O2), and COT, did not change the anorexic response to the exposure to hypobaric air. Depression of food intake during exposure to SHA also occurred in rats fasted during 31 h before exposure and allowed to eat ad libitum for 2 h during exposure. Body mass loss was similar in 48-h fasted rats that were either hypoxic or normoxic. Body mass loss was similar in normoxic and hypoxic rats, the former eating the amount of food freely eaten by the latter. Hypoxia-acclimated rats with endogenously induced polycythemia taken to SHA again had diminished food intake and lost body mass at rates that were very close to those found in nonacclimated ones. Exposure to SHA also led to a decrease in food consumption, body weight, and plasma leptin in adult female mice. Analysis of data suggest that body mass loss that accompanies SHA-induced hypoxia is due to hypophagia and that experimental manipulation of the blood oxygen transport capacity cannot ameliorate it. Leptin does not appear to be an inducer of the anorexic response to hypoxia, at least in mice and rats.

Topics: Acclimatization; Altitude Sickness; Animals; Anorexia; Appetite; Blood Gas Analysis; Body Weight; Fasting; Female; Hypoxia; Leptin; Mice; Oxygen; Polycythemia; Rats; Rats, Wistar; Reference Values

Topics: Adult; Altitude Sickness; Appetite; Humans; Leptin; Male; Mountaineering; Proteins; Weight Loss