Tracking the origin of obesity

One of the main contemporary questions of global interest is understanding the origin of obesity. While the scientific community is ardently discussing the issue, they have not yet come up with a single answer. There is consensus, however, that this metabolic imbalance is of interest to both public health and the economy. In recent decades, the prevalence of obesity and type 2 diabetes has increased everywhere.


Since individual behaviors hardly may influence statistics, there is agreement that obesity is the result of interactions between the genetic information of the organism, known as its genotype, and the environment, including cultural behavior patterns. For some authors, behavioral patterns are the key to the phenomenon. However, it is logical to assume it also operates a certain predisposition to the development of obesity, which would be linked to our evolutionary past, although there is a wide debate on the precise nature of the processes that contributed to generating it.


One of the first hypotheses formulated to explain the genetic roots of this collective phenomenon was postulated in the early 1960s by the American geneticist James Neel (1915-2000). His theory is known today as the ‘thrifty genotype’ hypothesis, and suggests that obesity is a heritage from our ancestors in whom evolution favored genes that favor energy storage (those genes are said to have been positive selection object).


The thrifty genotype would have been beneficial to hunter-gatherer populations, as it would have allowed them to gain weight rapidly in times of plenty and be better adapted to survive in times of food shortages. This hypothesis is based on the idea, widespread in the literature on human evolution, that hunter-gatherer societies suffered more frequent famines than societies with other livelihoods, for example, farmers, and had to adapt to periods of food shortage. This genetic capacity to adapt to the periodic lack of food would then have favored the current obesity epidemic in populations in which said food shortage is no longer present.


However, there are few studies to support the claim that hunter-gatherers have suffered more hunger than other societies.


An alternative view, called the predation-release hypothesis, argues that the prevalence of the thrifty genotype would not be the result of positive selection for genes related to energy storage, but would result from having freed our species from the pressure caused by living under constant threat of natural predators.

This latter theory was formulated in 2007 by British biologist John Speakman of the University of Aberdeen, who argued that at the dawn of humanity about two million years ago, Homo habilis and Homo erectus (ancestors of modern humans) acquired the ability to use fire, to produce stone tools and weapons, and to group together in organized social structures. In this way, for the first time in the evolutionary history of animals, a species had the possibility to control and even eliminate the threat of predation.


The genotypes that are most successful at evading predators are those that confer speed, agility, endurance, athletic ability, and leanness. In the days when incipient humanity was subject to this threat of predation, these genotypes would have prevailed and even eclipsed those related to energy storage. But, once that threat disappeared, such genes were no longer indispensable for the survival and reproductive success of human beings. In the absence of selection pressure due to predation, genes that promote energy storage were not overshadowed or eliminated by natural selection: they simply drifted and facilitated the obesity pandemic in modern societies.


Although both the sparing genotype hypothesis and the predation release hypothesis have considerable merit, and perhaps account for a genetic predisposition to obesity in part of the human species, they do not decisively explain the contemporary pandemic in industrialized countries . This is due, among other reasons, to the fact that the genetic predisposition to obesity is not the same in the different ethnic groups, whose ancestors in turn experienced different environmental selection pressures.


It can be concluded, then, that both hypotheses would not be a faithful reflection of the events associated with human evolution, since both hypotheses assume that all individuals of the species would have been subjected to the same circumstances throughout their evolutionary history. This assumption does not consider the selection effect of the different and specific geographical conditions for which Modern humans transited from the time they left Africa some 70,000 years ago.


In those 70 millennia, modern humans spread across the globe: they populated Asia, Oceania, Europe, and America, where they inhabited a wide range of environments and climates. Large-scale studies have revealed a considerable number of genetic changes or variants that occurred as a result of natural selection that underwent the varied contemporary human populations in the last 10,000 to 15,000 years. These antecedents would suggest that exposure of diverse populations to differential environmental factors could be linked to genetic variants that confer different degrees of susceptibility to obesity. Some examples are changes that confer resistance to malaria in populations that live in defined geographic areas, or that favor lactose digestion, or that modify skin pigmentation, and even influence susceptibility to HIV infection.


Scientists recently postulated that the ability to regulate body temperature in extreme hot or cold climates confers a powerful survival advantage. In this sense, the genes responsible for thermoregulation would be of greater importance than thrifty genes, since they would allow an individual to survive to reach reproductive age. One of the main driving forces behind the global spread of mammals, 65 million years ago, is believed to be the ability to produce heat through specific proteins present in brown adipose tissue. This ability is thought to have contributed to placental mammals inhabiting every corner of the globe.


At the time of birth, human babies possess abundant amounts of brown fat, which represents 1.4% of their total body weight and plays a critical role in the thermal regulation of infants and young children. Brown adipose tissue is capable of generating heat thanks to a process known as thermogenesis. The energy produced by the mitochondria is released in the form of heat instead of being used to generate ATP, a process by which the body consumes stored triglycerides, breaking them down into their constituents, glycerol and free fatty acids. Therefore, an increase in the expression of genes linked to the metabolism of brown adipose tissue would confer an adaptive advantage in cold climates.


The ancestors of modern humans (Homo sapiens) and Neanderthals (Homo neanderthalensis) separated from a common ancestral population between 800,000 and 400,000 years ago. Neanderthal man is an extinct species of the same genus as us, who inhabited Europe and parts of Western Asia from about 230,000 years ago to about 30,000 years ago. It was a species well adapted to the extreme cold of the fourth and last ice age. It was long assumed that the most successful migration of modern humans out of Africa dates back to around 70,000 years ago, as inferred from archaeological and genetic records. However, it is currently believed that there were waves more than 100,000 years ago, that populated Oceania and some regions of the Americas, although those that reached America would have become extinct and would not be ancestors of current populations. Modern humans quickly spread to all continents and coexisted with Neanderthals in Europe and Central Asia for thousands of years.


There is evidence that fragments of the Neanderthal genome persist in contemporary humans, showing that there were crosses between both species. Comparative studies of the nuclear genome of remains of both species indicate, in effect, that current human populations settled outside sub-Saharan Africa contain genomic regions very similar to those of the Neanderthal. In each individual, these regions represent between 1 and 4% of the total genome. It is striking that while this frequency is approximately constant in all populations today living outside of Africa, the proportion of the Neanderthal genome is tripled in populations of European descent in genes related to lipid catabolism. Arguably, then, the genetic variants that evolved in Neanderthals would have given a selective advantage to modern humans who settled in the same geographic areas.

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