Comp. by: PG1812 Stage : Proof ChapterID: 9780521879484c30 Date:23/3/10 Time:19:49:40 Filepath:H:/ 01_CUP/3B2/Muehlenbein-9780521879484/Applications/3B2/Proof/9780521879484c30.3d 30 Beyond Feast–Famine: Brain Evolution, Human Life History, and the Metabolic Syndrome Christopher W. Kuzawa EXPLAINING THE MODERN METABOLIC 2008). The idea that obesity and related diseases result DISEASE EPIDEMIC: THE THRIFTY GENOTYPE from a “discordance” or “mismatch” between our HYPOTHESIS AND ITS LIMITATIONS ancient genes and our rapidly changing lifestyle and diet is now widely accepted, and it seems clear that Today, more than 1 billion people are overweight or obesity must be more common today in large part obese, and the related condition of cardiovascular dis- because we are eating more and expending less than ease (CVD) accounts for more deaths than any other our ancestors traditionally did (Eaton and Konner, cause (Mackay et al., 2004). Why this epidemic of 1985; see Chapter 28 of this volume). Despite the intui- metabolic disease has emerged so rapidly in recent tive appeal of these ideas, the hypothesis is not without history is a classic problem for anthropologists con- limitation. For one, it helps explain why we gain weight cerned with the role of culture change in disease in a modern environment of nutritional abundance, transition (Ulijaszek and Lofink, 2006). In 1962, the but says very little about the syndrome of metabolic geneticist James Neel proposed an explanation for this changes that account for the diseases that accompany phenomenon that looked for clues in the “feast– obesity (Vague, 1955; Kissebah et al., 1982). While famine” conditions that he believed our nomadic, for- excess weight gain in general is unhealthy, it is specif- aging ancestors faced in the past. Given the unpredict- ically fat deposition in the visceral or abdominal region ability of food resources in natural ecologies, Neel that accounts for the bulk of its adverse effects on suggested that a “thrifty” metabolism capable of effi- health. Visceral fat has unique metabolic properties ciently storing excess dietary energy as body fat when that contribute to prediabetes states like insulin resist- food was abundant would have provided a survival ance when deposition in this depot is excessive advantage during later periods of shortage. In the wake (Reaven, 1988; Wellen and Hotamisligil, 2003). The of the rapid dietary and lifestyle change in recent gen- simple idea that our bodies are famine adapted may erations, and the comparatively slow pace of genetic help explain why we are prone to gaining weight when change, these foraging-adapted genes would now be we eat too much, but it says little about the metabolic “rendered detrimental by progress” (Neel, 1962), symptoms that make weight gain unhealthy. leading to obesity and diabetes. While a useful way to The sole focus of the hypothesis on genes is also think about obesity generally, variations on this idea outdated in light of newer evidence that biological sus- have been proposed to help explain the high rates of ceptibility of developing these adult diseases is also metabolic disease among populations believed to have elevated among individuals who experienced poor experienced especially severe nutritional conditions in nutrition during early life (Barker et al., 1989; Gluck- the past, including the diabetes-prone Pima Indians of man and Hanson, 2006). A large research literature has the American Southwest (Knowler et al., 1982), and demonstrated that the body’s responses to early life several groups of South Pacific Islanders who have nutrition subsequently influences that individual’s risk among the highest rates of obesity in the world (Dowse for developing adult diseases like diabetes and CVD, and Zimmet, 1993; McGarvey, 1994). a process described as nutritional “programming” The thrifty gene hypothesis was one of the first uses (Lucas, 1991) or “induction” (Bateson, 2001). For of evolutionary reasoning to shed light on a human instance, CVD and the rate of CVD mortality in adult- disease, and is thus a classic example of evolutionary hood are inversely related to size at birth – a measure or “Darwinian” medicine (see Nesse and Williams, of fetal nutrition – in places like the UK, Sweden, 1994; Stearns and Koella, 2008; Trevathan et al., India, and the Philippines (Kuzawa and Adair, 2003; Human Evolutionary Biology, ed. Michael P. Muehlenbein. Published by Cambridge University Press. # Cambridge University Press 2010. 518 Comp. by: PG1812 Stage : Proof ChapterID: 9780521879484c30 Date:23/3/10 Time:19:49:40 Filepath:H:/ 01_CUP/3B2/Muehlenbein-9780521879484/Applications/3B2/Proof/9780521879484c30.3d Beyond Feast–Famine: Brain Evolution, Human Life History, and the Metabolic Syndrome 519 16 14 12 10 8 % body fat 6 4 2 0 Cat Pig Rat Lamb Calf Foal Mouse Rabbit Human Fur seal Baboon Caribou Sea LionsReindeer Hamster Guinea Harppig seal Black bear Elephant seal 30.1. Percentage of body fat at birth in mammals. Adapted from Kuzawa (1998). Yajnik, 2004; Lawlor et al., 2005). Individuals who 30 were born small also experience durable changes in biological systems that contribute to CVD, as reflected 25 Male in their higher risk of depositing fat in the visceral Female region, or of developing high blood pressure, impaired 20 glucose tolerance or diabetes, or high cholesterol (Adair 15 et al., 2001; Kuzawa and Adair, 2003). When the dietary intake of pregnant rats and sheep is restricted, their % body fat 10 offspring have much the same set of outcomes as we see in humans born small (McMillen and Robinson, 5 2005; Fernandez-Twinn and Ozanne, 2006). This finding 0 suggests that the body has an ability to induce a “thrifty 0 12243648607284 phenotype” that is better suited to survival in nutrition- Age (months) ally challenging environments. It also illustrates why a 30.2. purely gene-based model of metabolic disease evolution Age changes in percentage body fat in humans. Data from Davies and Preece (1989), pp. 95–97. is incomplete (Hales and Barker, 1992). A third limitation of the thrifty genotype hypothesis is that it merely assumes that famine was the key source of selection on human metabolism without con- mammal studied thus far (Kuzawa, 1998). This is sidering the actual causes of that stress and the ages at followed by a continued period of rapid fat deposition which it is most severe (Kuzawa, 1997). There are during the early postnatal months. In well-nourished reasons to question whether our distant foraging populations, adiposity reaches peak levels during the ancestors experienced a major burden of famine, first year of life before gradually declining to a nadir in which archaeological and contemporary ethnographic childhood, when humans reach their lowest level of data suggest only emerged as an important problem body fat in the lifecycle (Figure 30.2). If the threat of after the evolutionarily recent development of agri- famine is what drove the human tendency to build up cultural subsistence (Cohen and Armelagos, 1984; fat reserves, it is not obvious why children’s bodies Benyshek and Watson, 2006). Given this, famine may should do so little to prepare for these difficult periods. have been a relatively weak force of selection on the The lower priority placed upon maintaining an energy human gene pool (Speakman, 2006). reserve by middle childhood suggests that the back- Additional support for this interpretation comes ground risk of starvation faced by our ancestors – from the growth pattern of body fat in humans, shown “famine” – was small in comparison to the nutritional in Figure 30.1. In humans, body fat makes up a larger stress experienced during the preceding developmental percentage of weight at birth than in any other period. A prereproductive life history stage that does Comp. by: PG1812 Stage : Proof ChapterID: 9780521879484c30 Date:23/3/10 Time:19:49:42 Filepath:H:/ 01_CUP/3B2/Muehlenbein-9780521879484/Applications/3B2/Proof/9780521879484c30.3d 520 Christopher W. Kuzawa not prioritize energy storage is difficult to reconcile 100 with the assumption that famine was the major nutri- tional challenge faced by human populations. 80 In this chapter, I review the causes, consequences, and adaptive solutions to the nutritional stress of 60 infancy and childhood in hopes of shedding light on the evolution of human metabolism. Viewing human 40 nutritional stress through a developmental lens helps % RMR to brain identify ages when human metabolism has likely been 20 under strongest selection. I will show how two traits 0 that are central to the adverse health consequences 0 5 10 15 20 of obesity in overnourished adults – visceral fat and Age (years) insulin resistance – likely evolved as components of 30.3. Percentage of resting metabolic rate (RMR) devoted to an energy backup system that reprioritizes the alloca- the brain by age in humans. Data adapted from Holliday (1986). tion of prized energy and glucose during a crisis, thus allowing the body to shunt resources from nonessen- tial functions to critical organs like the brain (for dis- which requires a constant redistribution of ions across cussion of the function of insulin resistance during the cell membrane using energy-dependent ion pumps. pregnancy, see Haig, 1993). Demands placed on this Humans are exceptional in the quantity of this costly system are greater during infancy and early childhood tissue that they must sustain, and it has been estimated than at any other age of the lifecycle, suggesting that that greater than 80% of the body’s metabolism is some of the evolutionary seeds of adult metabolic dis- devoted to the brain in the newborn (Figure 30.3). ease may trace to selection pressures operative during It is a notable feature of human metabolism that early life. In addition, evidence for developmental total metabolic rate measured in adulthood (for plasticity in this backup system and the adult diseases instance, calories expended per day) is not increased that it contributes to suggests that its priorities may be above other mammals of similar body size despite adjusted in response to nutritional and other stressors our highly encephalized state (Armstrong, 1983).