Hypoxia, nitrogen balance and body weight

Abstract

Recent clinical studies have shown that acute exacerbations of chronic obstructive pulmonary disease (COPD) are characterised by disturbances in the balance between dietary intake and energy expenditure [1,2] as well as by a negative nitrogen balance [3]. Since weight loss prior to and during hospitalisation for an acute exacerbation has been related to poor outcome in terms of mortality and readmission rate [4,5], it is important to prevent or treat this complication. It is yet unclear to what extent factors contributing to weight loss, during acute disease exacerbations, are similar to stable disease. Elevated energy requirement of physical activity has been implicated during stable disease [6] but is unlikely to be an important factor during acute disease, when the activity level is probably very low. Hypoxia is otherwise implicated as a potential trigger of reduced dietary intake and metabolic alterations during acute exacerbations, while in stable disease, there is no strong relationship between resting arterial oxygen tension and nutritional status.Hypobaric hypoxia, as applied in high-altitude studies, clearly induces weight loss and is an interesting human model to investigate the influence of acute hypoxia. There is evidence that the altitude limit for the maintenance of body weight in humans isy5,000 m [7]. Acute transfer from sea level to altitude usually results in weight loss, but the rate of weight loss diminishes when the food supply is adequate. Reduced dietary intake is initially the result of a reduced meal size because of a rapid increase in satiety during the meal [8]. Part of the effect of reduced meal size on daily dietary intake can be compensated for by an increase in meal frequency. At altitudes of o7,000 m, acute mountain symptoms result in suppression of hunger and the desire to eat [8], possibly related to a reduction in appetite through leptin, a key mediator in the neuroendocrine regulation of food intake [9]. The effect of hypobaric hypoxia on resting metabolic rate is unclear. High-altitude studies are limited by the fact that subjects are often highly trained and have a physical activity related energy expenditure that is comparable to that of endurance athletes. A more specific study on nitrogen balance during a prolonged stay at 5,000 m showed no impairment of protein digestibility [10]. However, glycine metabolism, as measured with glycine ( 15 N), changed as a function of altitude exposure. Urinary excretion of 15 N from intravenous glycine administration, as a fraction of urinary nitrogen, increased from 20.6% after 4 days to 38.0% after 13 days at altitude (pv0.05). It was hypothesised that the increased 15 N excretion was due to increased oxidation of glycine as a function of altitude exposure. Others have also observed an altitude-induced increase in capillary leakage resulting in a renal loss of amino acids [11].Experimental models subjecting animals to a hypoxic environment, i.e. that of IIOKA et al. [12] in the current issue of this journal, are comparable to an altit...

Upper airway loading induces growth retardation and change in local chondrocyte IGF-I expression is reversed by stimulation of GH release in juvenile rats

“…Similar to previous studies, we did not find evidence for hypoxia (12,13,37,44). Hypoxia can serve as an additional potential trigger of reduced dietary intake (7,16,38) and decreased circulating IGF-I and IGF-binding protein (IGFBP)-3 (4,18,26,27). Further studies are needed to determine whether CAL induces oxidative stress and activation of proinflammatory processes in the respiratory muscles.…”

Role of Orexin in Respiratory and Sleep Homeostasis during Upper Airway Obstruction in Rats

“…5,6,[8][9][10] Chronic hypoxia can reduce food intake and induce erythropoiesis. 33,34 In this study hemoglobin and lactate levels were similar to those of controls, confirming previous findings, 6,8-10 and dietary intake was significantly higher. 6 In children, however, oxygen saturation may decrease with airway loading during sleep.…”

Chronic upper airway resistive loading induces growth retardation via the GH/IGF-I axis in prepubescent rats

“…Hypoxia can serve as a potential trigger of reduced dietary intake (8,15,30) and decreased circulating IGF-I and IGFBP-3 (5,16,21,22). Total body energy balance (V O 2 /daily food intake), hemoglobin and lactate levels, and arterial oxygenation were similar to those of the control group, within normal physiological range (12,27).…”