Loss of body mass and exercise intolerance are common findings in chronic obstructive pulmonary disease and are often difficult to reverse despite optimal nutritional intake. Similar findings have been reported in healthy individuals during high-altitude exposure. The role of hypoxia in modulating metabolism has been largely investigated in vitro and in animal studies. More fragmentary is the knowledge regarding hypoxia effects on in-vivo human metabolism. This paper reviews recent literature regarding the effects of chronic exposure to hypoxia on metabolism, particularly comparing chronic obstructive pulmonary disease patients with humans exposed to high altitude.
Hypoxia has important metabolic effects. Many oxygen-sensitive regulatory mechanisms work through hypoxia inducible factor 1, and recent literature regarding the hypoxic stimulus and its pathological implications deals largely with hypoxia inducible factor 1-related findings. Hypoxia inducible factor 1 is pivotal in the adaptation to chronic hypoxia: it induces gene expression for fructose-2-6-biphosphatase, an enzyme switching glucose metabolism towards glycolysis, allowing energy production in anaerobic conditions. Hypoxia inducible factor 1 is also involved in the development of anorexia because it induces the promoter of the leptin gene. Particularly important for future therapeutic implications are findings related to hypoxia inducible factor 1 polymorphism and interaction with other molecules, especially estrogens, in the clinical evolution of disease.
Malnutrition is a worsening factor in chronic obstructive pulmonary disease. Similarities between chronic obstructive pulmonary disease and altitude exposure point to the importance of hypoxia in this regard. A better understanding of the underlying mechanisms will help to find alternative therapeutic approaches.