Ascent to altitude as a weight loss method: The good and bad of hypoxia inducible factor activation

Abstract

Objective Given the epidemic of obesity worldwide there is a need for more novel and effective weight loss methods. Altitude is well known to be associated with weight loss and has actually been used as a method of weight reduction in obese subjects. This review demonstrates the critical role of hypoxia inducible factor (HIF) in bringing about the reduction in appetite and increase in energy expenditure characteristic of hypobaric hypoxia Design and methods A MEDLINE search of English language articles through February 2013 identified publications associating altitude or hypobaric hypoxia with key words to include hypoxia inducible factor, weight loss, appetite, basal metabolic rate, leptin, cellular energetics, and obesity. The data from these articles were synthesized to formulate a unique and novel mechanism by which HIF activation leads to alterations in appetite, basal metabolic rate, and reductions in body adiposity. Results A synthesis of previously published literature revealed mechanisms by which altitude induces activation of HIF, thereby suggesting this transcription factor regulates changes in cellular metabolism/energetics, activation of the central nervous system, as well as peripheral pathways leading to reductions in food intake and increases in energy expenditure. Conclusions Here we present a unifying hypothesis suggesting that activation of HIF under conditions of altitude potentially leads to metabolic benefits that are dose dependent, gender and genetic specific, and results in adverse effects if the exposure is extreme.

Impact of intermittent hypoxia and exercise on blood pressure and metabolic features from obese subjects suffering sleep apnea-hypopnea syndrome

“…Indeed, altitude induces HIF activation, leading to changes in cellular metabolism and the activation of peripheral pathways and the central nervous system affecting energy expenditure and appetite pathways [35].…”

Increased Cardiometabolic Risk and Worsening Hypoxemia at High Altitude

“…Interestingly, many adaptations to tissue hypoxia in muscle theoretically facilitate glucose disposal, an effect witnessed both in vivo (Mackenzie et al, 2011(Mackenzie et al, , 2012 and in vitro (Azevedo et al, 1995). Hypoxia facilitates angiogenesis (Iyer et al, 1998), which increases tissue glucose delivery; facilitates glucose transport through upregulation of GLUT1 and GLUT4 (Chou et al, 2004;Sakagami et al, 2014); upregulates AMPactivated protein kinase, which increases insulin sensitivity (Kahn et al, 2005); and shunts glucose toward glycolysis and lactate pathways rather than mitochondrial oxidation (Wheaton et al, 2011), resulting in higher total body glucose flux (Roberts et al, 1985;Palmer et al, 2014). Many of these changes are facilitated, in whole or in part, by HIF-1a (Semenza, 1999).…”

Ultraviolet radiation, vitamin D and the development of obesity, metabolic syndrome and type-2 diabetes

“…Increased altitude may also reduce fasting glucose levels and improve glucose tolerance (reviewed by 74,76 ). The most likely explanation of these observations is thought to be increased hypoxia (reduced atmospheric oxygen levels) 76,77 , with less recognition for other environmental effects of increased altitude, such as greater UVR. Conversely, there are reports of dyslipidemia and increased cardiovascular disease risk at higher altitudes.…”