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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\u2010sensitive potassium (K<jats:sub>ATP<\/jats:sub>) 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.<\/jats:p><jats:p>Also watch the <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/youtu.be\/qOqYkfoLJNQ\">Video Abstract<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bies.201400042","type":"journal-article","created":{"date-parts":[[2014,6,11]],"date-time":"2014-06-11T09:54:54Z","timestamp":1402480494000},"page":"721-729","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["How wasting is saving: Weight loss at altitude might result from an evolutionary adaptation"],"prefix":"10.1002","volume":"36","author":[{"given":"Andrew J.","family":"Murray","sequence":"first","affiliation":[{"name":"Department of Physiology Development &amp; Neuroscience 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