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

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 setpoint, 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.

Foetal and childhood exposure to famine and the risks of cardiometabolic conditions in adulthood: A systematic review and meta‐analysis of observational studies

“…The body fat hypothesis has been proposed to explain sex differences in life expectancy . Stored body fat serves as the major energy reserves during negative energy balance . Sexual dimorphism in human body composition is widely recognized, with adult men having higher skeletal muscle mass and lower fat mass than women .…”

“…Stored body fat serves as the major energy reserves during negative energy balance . Sexual dimorphism in human body composition is widely recognized, with adult men having higher skeletal muscle mass and lower fat mass than women . Therefore, women are expected to carry higher energy reserves.…”

The unidentified hormonal defense against weight gain

“…Solid evidence supports that low circulating leptin acts as a strong starvation signal by potentiating appetite and protecting against a dangerous degree of thinness [7,32,33]. Consequently, leptin is considered an important mediator of the lower intervention point [31] (Fig 2). Although research into this aspect of body weight regulation has revealed one explanation why it is so difficult to maintain a large weight loss [3], it provides no clue as to why some individuals become obese in the first place.…”

“…Because physiological regulators are less active within this zone, fat mass can fluctuate freely until it "bounces into" either the upper or lower boundary. When this happens, powerful biological feedback forces are engaged to ensure that adipose depot size does not change to an extent that jeopardizes the ability to escape from lifethreating dangers or to survive periods of starvation and sickness-induced anorexia [31]. Solid evidence supports that low circulating leptin acts as a strong starvation signal by potentiating appetite and protecting against a dangerous degree of thinness [7,32,33].…”

“…However, once our ancestors refined social behavior and collaboration and invented fire and weaponry, they rose to the top of the food chain, suggesting that the evolutionary forces that used to limit adiposity were suddenly no longer favored. Because of the subsequent lack of selection pressure, the encodings of the upper intervention point became subject to erosion by random mutations, and as a result, we now differ widely in terms of defending ourselves against a prolonged excessive energy intake [29][30][31]37]. This differential response is clearly evident in both natural experiments and in controlled human overfeeding interventions.…”