Murray, AJ;
Montgomery, HE;
(2014)
How wasting is saving: Weight loss at altitude might result from an evolutionary adaptation.
BioEssays
, 36
(8)
pp. 721-729.
10.1002/bies.201400042.
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Abstract
At extreme altitude (>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 (KATP) 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.
| Type: | Article |
|---|---|
| Title: | How wasting is saving: Weight loss at altitude might result from an evolutionary adaptation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/bies.201400042 |
| Publisher version: | http://dx.doi.org/10.1002/bies.201400042 |
| Language: | English |
| Additional information: | � 2014 The Authors. Bioessays published by WILEY Periodicals, Inc. This is an www.bioessays-journal.com open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biology, Life Sciences & Biomedicine - Other Topics, amino acids, catabolism, hypoxia, ketones, metabolism, muscle, D-BETA-HYDROXYBUTYRATE, K-ATP CHANNELS, ISCHEMIA-REPERFUSION INJURY, HUMAN SKELETAL-MUSCLE, KETONE-BODIES, PROXIMAL TUBULES, KETOGENIC DIET, AMINO-ACIDS, RAT-BRAIN, PRACTICAL IMPLICATIONS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1443407 |
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