Obese humans as economically designed feed converters: symmorphosis and low oxidative capacity skeletal muscle.
Human obesity is considered a consequence of a thrifty or economic metabolism. In this hypothesis, we apply an established economic design theory, called symmorphosis, to help explain the known association between obesity and low oxidative capacity skeletal muscle. Symmorphosis reflects an engineering principle, and predicts that physiological systems are most economically designed when unnecessary spare capacity is eliminated. This is because the structural/functional adaptations accounting for spare capacity themselves bear energetic costs of construction, maintenance and load. As oxidation of feed energy occurs in mitochondria, and because skeletal muscle accounts for 30% of resting metabolism, we focus on skeletal muscle mitochondria. In the same way that the most economically designed elevator is supported by a cable that is strong enough, but not too strong, symmorphosis predicts that the most economically designed feed converters should have enough, but not too much mitochondrial oxidative (fuel burning) capacity. While ATP demand is clearly more efficiently met by oxidative (38 molecules of ATP) rather than glycolytic (2 molecules of ATP) metabolism, symmorphosis predicts that having excess oxidative capacity actually reduces feed efficiency. This inefficiency is manifest by having to maintain, ultimately using feed energy, the expensive inner mitochondrial proton gradient in the superfluous mitochondria. On this basis, we predict that established molecular controllers of mitochondrial biogenesis and oxidative capacity such as eNOS, SIN3 co-repressor, TFAM and PPARgamma may yield useful DNA markers and therapeutic targets for issues relating to frugal energetics, namely predisposition to obesity and starvation resilience.
CSIRO Livestock Industries, Queensland Bioscience Precinct, 306 Carmody Road, Brisbane, Queensland, Australia. nicholasjameshudson@yahoo.com
Nicholas J
NJ
Hudson
Sigrid A
SA
Lehnert
Gregory S
GS
Harper
D004734:Energy Metabolism; D005502:Food; D006801:Humans; D008931:Mitochondria, Muscle / Q000502:physiology; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009765:Obesity / Q000503:physiopathology*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption