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How wasting is saving: Weight loss at altitude might result from an evolutionary adaptation
Author(s) -
Murray Andrew J.,
Montgomery Hugh E.
Publication year - 2014
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.201400042
Subject(s) - catabolism , wasting , hypoxia (environmental) , ketone bodies , cachexia , weight loss , amino acid , skeletal muscle , biology , endocrinology , medicine , appetite , reactive oxygen species , metabolism , microbiology and biotechnology , chemistry , biochemistry , oxygen , obesity , organic chemistry , cancer
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 (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. Also watch the Video Abstract .