The Early Life Origins of Obesity Related Health Disorders. New Discoveries Regarding the Intergenerational Transmission Of
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AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 57:79–93 (2013) The “Early Life” Origins of Obesity-Related Health Disorders: New Discoveries Regarding the Intergenerational Transmission of Developmentally Programmed Traits in the Global Cardiometabolic Health Crisis Daniel C. Benyshek* Department of Anthropology, University of Nevada, Las Vegas, Las Vegas, NV 89154-5003 KEY WORDS “cardiometabolic syndrome”; epigenetics; multigenerational; transgenerational ABSTRACT Popular media reports concerning the developmental processes and capacities in health and dis- causes of the current global obesity pandemic and its ease even further by investigating the transmissible related sequelae—the cardiometabolic syndrome—are nature of developmentally programmed cardiometabolic often couched in terms of dramatic changes in diet and traits to subsequent generations. In this review, after lifestyle around the world; namely, drastically increasing briefly revisiting the fundamental discoveries of first- dietary intakes of high energy foods and plummeting lev- generation DOHaD research, I consider how recent discov- els of daily physical activity—the hallmarks of the so eries regarding the transmissibility of developmentally called “nutrition transition.” Far less attention is generally acquired traits are providing new insights into the current drawn to the important role phenotypic plasticity during global cardiometabolic pandemic, and how a better under- early life (i.e., “developmental programming”) plays in the standing of developmental programming—including cardiometabolic health crisis. Recently, however, research- transmissibility—are essential for the conceptualization ers working within the field of the developmental origins and implementation of public health initiatives aimed at of health and disease (DOHaD) and epigenetics have stemming this global health crisis. Am J Phys Anthropol extended our understanding of the role played by these 57:79–93, 2013. VC 2013 Wiley Periodicals, Inc. A recent study describing the shifting global burden of ity risk associated with more modest levels of adiposity disease from 1990 to 2010 reports that global mortality (corresponding to the common body mass index classifi- due to malnutrition and infectious diseases, such as cations of “overweight=preobese” [BMI of 25–29.9] and tuberculosis, had fallen sharply during the report’s “class 1 obesity” [BMI of 30–34.9]) may have been over- twenty year study period, while death from diseases stated (Flegal et al., 2013), obesity remains a major risk that typically strike in older age and wealthier societies, factor for Type 2 diabetes, cardiovascular disease, and such as heart disease, showed dramatic increases (Loz- hypertension—the major components of the cardiometa- ano et al., 2012). The report cites improvements in sani- bolic syndrome. This is problematic given that, according tation, childhood immunization programs, and access to to the World Health Organization, “an escalating global food as largely responsible for the shift. As infant mor- epidemic of overweight and obesity—‘globesity’—is tak- tality and infectious diseases have fallen around the ing over many parts of the world” (WHO, 2013), in some world, however, deaths due to obesity-related diseases cases, paradoxically, even in contexts of “food insecurity” have risen sharply; diabetes mortality, for example, (Velasquez-Melendez et al., 2011). doubled during the study period. This, even as malnutri- Obesity was first recognized as an important chronic tion (due to poor quality diets) remains an intractable disease risk factor in the 1970s (Keys et al., 1972) when problem in much of the economically developing world its association with cardiovascular disease was first (FAO, 2012), often existing side by side with (energy) noted, and by the late 1990s obesity-related metabolic over-nutrition, a situation commonly referred to as the diseases like Type 2 diabetes were viewed as a major “dual burden of malnutrition” (Doak et al., 2004). These threat to global health (King et al., 1998). In the earliest recently identified shifts in mortality reflect, in part, the stages of what would later become known as the global health consequences of the two co-existing patterns asso- obesity pandemic, many scientists believed that the ciated with the global “nutrition transition” (Popkin, 2006): one characterized by low quality=low variety diets consisting of starchy, low fat, high fiber foods, and coupled with labor intensive physical activity and stunt- *Correspondence to: Daniel C. Benyshek, Department of Anthro- pology, University of Nevada, Las Vegas, 4505 Maryland Parkway, ing (Fig. 1 [Stage 3]); the other by diets and lifestyles Box 455003, Las Vegas, NV 89154-5003, USA. E-mail: marked by highly processed inexpensive foods—high in [email protected] energy, simple sugars, and saturated fat, while low in fiber—coupled with sharply declining levels of physical DOI: 10.1002/ajpa.22393 activity in both work and leisure settings, and increas- Published online in Wiley Online Library ing levels of obesity (Fig. 1, [Stage 4]). While the mortal- (wileyonlinelibrary.com). Ó 2013 WILEY PERIODICALS, INC. 80 D.C. BENYSHEK Fig. 1. Stages 3–5 of the nutrition transition. Stage 3 and Stage 4 currently characterize the two dietary, physical activity, and morbidity patterns associated with the “dual burden” of malnutrition. (Reproduced with permission from Popkin, Am J Clin Nutr, 2006, 84, 289–298VC American Society for Nutrition). propensity to accumulate excess body fat (among other by most members of the scientific and medical commun- dysregulated “thrifty” metabolic features) was strictly ities, and it remains widely cited today1. determined by the interaction of genotype and “lifestyle” Beginning in the late 1980s, an alternative view to the (i.e., dietary and physical activity) risk factors (Neel, 1962, narrowly construed genetic predisposition model of the 1982, 1999; Ritenbaugh and Goodby, 1989). The relative thrifty genotype hypothesis emerged, one that could bet- frequency of the so called “thrifty genotype” in human pop- ter account for the extent and pace of shifts in global ulations was thought to vary largely along racial=ethnic morbidity and mortality patterns that would eventually lines, and was believed to reflect the different nutritional be recognized as the global obesity=cardiometabolic pan- histories and food economies of these groups over many demic. This was the “thrifty phenotype hypothesis,” millennia. Natural selection, it was thought, would have which, by recognizing the importance of critical windows favored thrifty genotypes among human groups experienc- of growth and development in human health and disease ing regular and severe “feast or famine” cycles of food during adulthood, offered an alternative explanation for availability, due to their hunter–gatherer food economies, what may only have appeared to be a (genetically) herit- harsh local ecology, or lengthy and arduous migrations able component to obesity and cardiometabolic health (Diamond, 1992, 2003). As a result, by the 1980s, several problems among the highest risk populations. This ulti- “thrifty genotype” populations including American Indi- mately opened the door for a new paradigm for under- ans, Pacific Islanders, and Aboriginal Australians had standing chronic disease risk that moves beyond been identified, and their staggering and growing preva- simplistic (and inadequate) genetic or lifestyle explana- lence of obesity and Type 2 diabetes were seen by most tions, and instead offers a more integrated approach human biologists and geneticists as the direct consequence that incorporates genetic heritability and lifestyle factors of their common genetic predisposition for a thrifty metab- such as diet and activity levels into the analysis of olism that would preferentially “store fat and spare human health, but that also recognizes the role played glucose.” The genetic predisposition that once ensured by a powerful capacity in nature—developmental plastic- their ancestors’ survival, the theory suggested, now pre- ity—the ability of a gene to generate a range of possible disposed their descendants to obesity and Type 2 diabetes phenotypes depending on environmental experience. even as they transitioned to obesogenic western diets and lifestyles (Neel, 1999). Twenty years after its original for- THE DEVELOPMENTAL ORIGINS OF mulation, the thrifty genotype hypothesis was embraced CARDIOMETABOLIC DISEASE Although the relationship between deprivation in childhood and increased adult mortality had been noted 1At the same time, the shortcomings of the model have increasingly decades earlier (see Kermack et al., 1934; Forsdahl, become apparent. Although recent genomic research does provide 1977), the association between poor maternal diet during some evidence of population-specific and metabolically-based genetic pregnancy (expressed as low birth weight offspring) and variants, as predicted by the model, these specific alleles have very adult cardiometabolic dysfunction (especially when diet small effect sizes. Thus, while some findings from genomic analyses have proven to be consistent with the thrifty genotype model, the had improved in adulthood) was only being discovered at “thrifty genes” identified by genetics research appear to fall well short this time by researchers in England. Drawing on sup- of accounting for population-based differences in cardiometabolic func- portive data from both retrospective epidemiological tioning and morbidity=mortality