If Body Fatness is Under Physiological Regulation, Then How Come We Have an Obesity Epidemic?

Abstract

Life involves a continuous use of energy, but food intake, which supplies that energy, is episodic. Feeding is switched on and off by a complex array of predominantly gut-derived peptides (and potentially nutrients) that initiate and terminate feeding bouts. Energy is stored as glucose and glycogen to overcome the problem of the episodic nature of intake compared with the continuous demand. Intake is also adjusted to meet immediate changes in demands. Most animals also store energy as fat. In some cases, this serves the purpose of storing energy in anticipation of a known future shortfall (e.g., hibernation, migration, or reproduction). Other animals, however, store fat in the absence of such anticipated needs, and in this case the fat appears to be stored in preparation for unpredictable catastrophic shortfalls in supply. Fat storage, however, brings disadvantages as well as advantages, in particular an increased risk of predation. Hence, many animals seem to have evolved a dual intervention point system preventing them from storing too little or too much fat. The physiological basis of the lower intervention point is well established, but the upper intervention point is much less studied. Human obesity can potentially be understood in an evolutionary context as due to drift in the upper intervention point following release from predation 2 million years ago (the drifty gene hypothesis) combined with a stimulus in modern society to overconsume calories, possibly attempting to satisfy intake of a limiting micro- or macro-nutrient like protein (the protein leverage hypothesis).