How wasting is saving: Weight loss at altitude might result from an evolutionary adaptation

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...

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Bibliographic Details
Published in:BioEssays 2014-08, Vol.36 (8), p.721-729
Main Authors: Murray, Andrew J., Montgomery, Hugh E.
Format: Article
Language:English
Subjects:
Acclimatization
Altitude
Amino acids
Animals
Biological Evolution
catabolism
Cell Hypoxia
Energy Intake
Energy Metabolism
Humans
Hypoxia
Insights & s
Ketone Bodies - physiology
ketones
Medical research
metabolism
muscle
Muscle, Skeletal - metabolism
Reactive Oxygen Species - metabolism
Signal Transduction
Weight Loss
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Summary: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. Also watch the Video . Sustained exposure to hypobaric hypoxia results in cachexia. Muscle breakdown releases amino acids, whilst hepatic ketogenesis converts fatty acids and some amino acids into ketone bodies. These act as metabolic substrates, but also as metabolic modulators, eliciting protective effects against hypoxic injury. Thus, we propose that hypoxia‐induced cachexia is protective.
ISSN:0265-9247
1521-1878
DOI:10.1002/bies.201400042