Failure of Polycythemia-Induced Increase in Arterial Oxygen Content to Suppress the Anorexic Effect of Simulated High Altitude in the Adult Rat

Abstract

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.

High altitude induced anorexia: Effect of changes in leptin and oxidative stress levels

“…Other workers also reported lower levels of circulating leptin on HA exposure. Norese et al (2002) have reported decreased leptin levels in mice exposed to simulated altitude of 4560 m and conclude that at least in case of rodents leptin is probably not causally implicated in the energy imbalance observed at HA. Lower levels of circulating leptin were observed in HA natives as compared to sea level residents (Woolcott et al 2002;Cabrera de Leon et al 2004).…”

Ghrelin and leptin levels of sojourners and acclimatized lowlanders at high altitude

“…However, studies on rodents exposed to simulated altitude have shown decreased leptin levels (Raff et al 1999, Norese et al 2002. Yasumasu et al (2002) have reported about 50% decreased leptin secretion in case of in vitro cultured adipocytes exposed to low oxygen concentration.…”

Leptin May Not Be Responsible for High Altitude Anorexia

“…Tschöp et al (1998) reported elevated serum leptin levels in human subjects at high altitude, and this was considered the mechanism of high altitude anorexia. However, results of subsequent studies on animal models and natives of different altitude appear to be contradictory (Norese et al, 2002;Woolcott et al, 2002).…”

“…In our study it was difficult to isolate the effect of cold and hypoxia, though the subjects were provided adequate protecting clothing. Norese et al (2002) have reported decreased leptin levels in female mice exposed to simulated high altitude (5460 m) with controlled temperature, and on the basis of their studies and other animal studies on rats, they concluded that, at least in case of rodents, leptin is not a player in altered energy homeostasis at high altitude that leads to anorexia and loss of body mass. Woolcott et al (2002) found a lower level of serum leptin in high altitude natives in comparison to sea-level residents.…”