The evolution of body fatness: trading off disease and predation risk

Abstract

ABSTRACT Human obesity has a large genetic component, yet has many serious negative consequences. How this state of affairs has evolved has generated wide debate. The thrifty gene hypothesis was the first attempt to explain obesity as a consequence of adaptive responses to an ancient environment that in modern society become disadvantageous. The idea is that genes (or more precisely, alleles) predisposing to obesity may have been selected for by repeated exposure to famines. However, this idea has many flaws: for instance, selection of the supposed magnitude over the duration of human evolution would fix any thrifty alleles (famines kill the old and young, not the obese) and there is no evidence that hunter-gatherer populations become obese between famines. An alternative idea (called thrifty late) is that selection in famines has only happened since the agricultural revolution. However, this is inconsistent with the absence of strong signatures of selection at single nucleotide polymorphisms linked to obesity. In parallel to discussions about the origin of obesity, there has been much debate regarding the regulation of body weight. There are three basic models: the set-point, settling point and dual-intervention point models. Selection might act against low and high levels of adiposity because food unpredictability and the risk of starvation selects against low adiposity whereas the risk of predation selects against high adiposity. Although evidence for the latter is quite strong, evidence for the former is relatively weak. The release from predation ∼2-million years ago is suggested to have led to the upper intervention point drifting in evolutionary time, leading to the modern distribution of obesity: the drifty gene hypothesis. Recent critiques of the dual-intervention point/drifty gene idea are flawed and inconsistent with known aspects of energy balance physiology. Here, I present a new formulation of the dual-intervention point model. This model includes the novel suggestion that food unpredictability and starvation are insignificant factors driving fat storage, and that the main force driving up fat storage is the risk of disease and the need to survive periods of pathogen-induced anorexia. This model shows why two independent intervention points are more likely to evolve than a single set point. The molecular basis of the lower intervention point is likely based around the leptin pathway signalling. Determining the molecular basis of the upper intervention point is a crucial key target for future obesity research. A potential definitive test to separate the different models is also described.