At the beginning of George Orwell's Animal Farm, we learn of the rebellious animals’ seven commandments, of which the last is the admirable statement that ‘all animals are equal’.1 By the end of the book, this commandment has been altered to read ‘all animals are equal but some animals are more equal than others’.1 So it is with body mass index (BMI). In general, increasing BMI is associated with increasing body fat content, but for any given BMI value South Asians tend to have substantially greater body fat, in particular abdominal fat, than Europeans.2 This enhanced abdominal adiposity is believed to play a key role in the greater susceptibility of South Asians to the metabolic syndrome.3
What can explain this population difference? In this issue, Sniderman and colleagues propose an explanation drawing on evolutionary biology.4 They note that adipose tissue consists of different compartments, and hypothesize that populations differ in the relative maximum size of these compartments. They suggest that the ‘primary’ subcutaneous compartment is larger in ‘whites’, allowing greater expansion in response to positive energy balance. In contrast, in South Asians they suggest the primary compartment is constrained, such that positive energy balance results in overflow to other compartments, with more serious health consequences. Looking for explanatory environmental factors, they suggest that heat stress over many generations might have constrained the primary compartment of the Asians.
The authors are right to search for an evolutionary explanation. Their notion of overflow, while consistent with physiological evidence, nevertheless seems simplistic. The greater central adiposity of South Asians compared with Europeans is by no means the only such ethnic difference. African-Americans have less visceral fat than white Americans despite a high prevalence of high BMI,5 but nonetheless are relatively insulin resistant and experience high rates of cardiovascular mortality.6 Hispanic Americans appear prone to central adiposity (Wells et al. unpublished data), but there is some suggestion that they may paradoxically experience lower rates of cardiovascular disease.6 Collectively, such studies indicate complex interactions between ethnicity, BMI, central obesity and mortality risk.
Whilst the harmful effects of an enlarged visceral fat depot are increasingly appreciated, the more fundamental functions of visceral fat have received minimal attention. Within any population, the contemporary profile of visceral fat must reflect its value to that population's ancestors in the past. Instead of considering the subcutaneous fat of South Asians to be constrained, we might rather view the allocation of surplus energy to competing adipose depots from a game theory perspective. The close association between catch-up growth as well as excess weight gain with greater visceral fat7 suggests that this depot is particularly sensitive to fluctuations in energy balance. Recent studies have demonstrated a greater level of genetic expression in visceral adipose tissue.8 In short, whilst clinicians view visceral adipose tissue as a source of harmful cytokines, an evolutionary approach illuminates it as a regulatory organ whose role becomes enhanced during malnutrition. It is plausible that South Asians allocate fat disproportionately to the visceral depot, not because other depots are constrained, but because in the absence of excess weight gain (a late 20th century phenomenon) chronic energy deficiency favours increased allocation to this depot. Support for this hypothesis comes from consideration of the history of South Asian populations.
The high levels of human body fat are commonly attributed to cycles of ‘feast and famine’ in our evolutionary past. Evidence for such cycles is rarely produced, and exactly when during our evolutionary heritage they might have occurred is rarely discussed. When seeking to explain population differences in adiposity, however, we must be dealing with a maximum timescale of around 150 000 years BP, when modern humans evolved. Although modern humans appear to have reached Asia around 50 000 years ago,9 the vast majority of population growth occurred in the last few thousand years, alongside the emergence of agriculture which significantly increased fertility rates. It is in the interaction between diverse agricultural practices and local climatic conditions that we should therefore search for the origins of ethnic differences in adipose tissue biology.
South Asians are merely one population amongst many that have been exposed to high levels of heat stress. What they have uniquely endured is wave after wave of famine, associated in turn with global climate patterns and geographic peculiarities. Agriculture in India is heavily dependent on the monsoon cycle.10 Each year the monsoons advance northwards across the Indian subcontinent and then return southwards, watering the fields abundantly on each occasion. Millions of rural farmers depend on this weather pattern for their subsistence, but at periodic intervals, climatic shifts attributable to El Niño alter the rain distribution with drastic consequences. In the words of the archaeologist Brian Fagan, ‘What happened when the unpredictable dark clouds never massed on the horizon and the monsoon failed? With almost mind-numbing regularity, Indian farmers died by the tens of thousands, sometimes millions … Famine was endemic in India for thousands of years, until railroads and improved communications made the shipment of grain and other food supplies to hungry villagers a practical relief strategy’.10 During the time of the British Raj, major famines occurred almost every decade, and are estimated to have killed 15 million people during Queen Victoria's reign alone.10
Fat is an energy store, and adipose tissue biology is selected in accordance with its capacity to buffer fluctuations in energy supply. I suggest that the specific stress of occupying an extremely volatile habitat for many generations, perhaps further exacerbated by dietary factors such as vegetarianism, has made the metabolism of South Asians substantially more sensitive to fluctuations in energy supply in comparison with other populations which have inhabited more stable environments, and that today's South Asians owe their very existence to the sensitive visceral fat of their ancestors. Importantly, however, South Asians are likely to lie near one extreme of a continuum, with differential exposure to ancestral climatic and ecological selective pressures shaping a contemporary continuum of differential ethnic susceptibility to specific components of the metabolic syndrome.
This hypothesis could be tested by categorizing populations according to indices of long-term environmental stability, and searching for associations between this ranking and adipose tissue biology. Famine was certainly no stranger to ancestral Europeans, but rarely exerted effects on a similar scale to that experienced regularly on the Indian subcontinent. Dairy farming vs rice agriculture, frequent vs occasional famines, seasonal vs non-seasonal environments, these are the background to ethnic variability in metabolism, and if we are to succeed in reducing ethnic disparities in heath, they merit serious study.