How wasting is saving: Weight loss at altitude might result from an evolutionary adaptation. (11th June 2014)

• Record Type: Journal Article
• Authors: Murray, Andrew J.; Montgomery, Hugh E.
• Is Part Of: BioEssays. Volume 36:Number 8(2014:Aug.)
• Page Start: 721
• Page End: 729
• Publication Date: 2014-06-11
• Subjects: Molecular biology -- Periodicals; Cytology -- Periodicals; Developmental biology -- Periodicals; 572.8
• DOI: 10.1002/bies.201400042
• Languages: English
• ISSNs: 0265-9247

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bies201400042-sec-0001" sec-type="section"> <p>At extreme altitude (&gt;5, 000 – 5, 500 m), sustained hypoxia threatens human function and survival, and is associated with marked involuntary weight loss (cachexia). This seems to be a coordinated response: appetite and protein synthesis are suppressed, and muscle catabolism promoted. We hypothesise that, rather than simply being pathophysiological dysregulation, this cachexia is protective. Ketone bodies, synthesised during relative starvation, protect tissues such as the brain from reduced oxygen availability by mechanisms including the reduced generation of reactive oxygen species, improved mitochondrial efficiency and activation of the ATP‐sensitive potassium (K_ATP) channel. Amino acids released from skeletal muscle also protect cells from hypoxia, and may interact synergistically with ketones to offer added protection. We thus propose that weight loss in hypoxia is an adaptive response: the amino acids and ketone bodies made available act not only as metabolic substrates, but as metabolic modulators, protecting cells from the hypoxic challenge.</p> <p>Also watch the <ext-link ext-link-type="uri" xlink:href="http://youtu.be/qOqYkfoLJNQ" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">Video Abstract</ext-link>.</p> </sec> </abstract>