At the University of Chicago, researchers have determined that several of the genetic variations that have helped human populations survive in colder climates may also increase the tendency for metabolic syndrome, a set of associated conditions including obesity, high cholesterol, heart disease, and diabetes.

Previously, scientists had often noted that humans in colder regions had bulkier builds and relatively shorter arms and legs. Researchers in the 1950s found correlation between cold climates and an increased body mass index (BMI), a measure of body fat based on weight and height. A study published in the February issue of the open-access journal PLoS Genetics, a part of the Public Library of Science, a correlation was found between climate and a number of the genetic variations that have previously appeared to influence metabolic syndrome. This is in harmony with the theory that adaptations to the colder climate involved these variants. That said, some of the genes associated with tolerance of colder weather have protective effects, while others increase the risk of the disease.

The authors emphasize the evolutionary history of such a set of genes. "Our earliest human ancestors lived in a hot humid climate that placed a premium on dispersing heat," said Anna Di Rienzo, a University of Chicago professor of human genetics. "As some populations migrated out of Africa to much cooler climates, there would have been pressure to adapt to their new settings by boosting the processes that produce and retain heat."

"Thousands of years later," she continued, "in an era that combines widespread central heating with an overabundant food supply, those genetic alterations have taken on a different sort of significance. They alter our susceptibility to a whole new set of diseases, such as obesity, coronary artery disease and type 2 diabetes."

The goal of the researchers was to find associations between the frequency of the genetic variations linked to metabolic syndrome and the variable related to climate in a population of samples worldwide. 82 genes were selected that were associated with energy metabolism, many of which had previously been attributed to disease risk, and looked for climate related variations in those genes. 1,034 subjects from 54 different populations were examined, and broad correlations between certain genes and colder climates were found. Climates were determined as measured by latitude as well as by summer and winter temperatures.

A leptin receptor, integral in appetite regulation and energy balance, was the source of one of the strongest signals of evolutionary selection. One version of this gene is common in locales with colder winters. This allele is additionally correlated with an increased respiratory quotient, the capability to absorb oxygen and expel carbon dioxide, which happens when the body produces heat. The same genetic variation has also been linked to a lower BMI, a smaller amount of abdominal fat, and a lower blood pressure. This specific leptin receptor, therefore, is protective against metabolic syndrome.

However, not all of the genes related to tolerance of colder climates protects against the metabolic syndrome. For example, an increased blood glucose level might protect the body from cold weather by making energy more readily available for production of heat. However, this also raises the risk of type 2 diabetes. FABP2 was a gene that was more prevalent in populations with lower temperatures actually increases BMA, promotes storage of fat in the body and increases levels of cholesterol. While this protects the body against the cold, it increases the risk of heart disease and diabetes, and thus metabolic syndrome.

The researchers have clearly identified genes associated with the cold weather, but there is mixed correlation with metabolic syndrome. "All these genes are likely to be involved in metabolic adaptations to cold climates," said Di Rienzo, "but they have opposing effects on metabolic syndrome risk. We suspect they spread rapidly as populations settled into colder and colder climates at higher latitudes, but in the modern era they have taken on a whole new significance, as the supply of calories from food has mushroomed and the survival advantage of generating more heat has been minimized by technology."

The writers then suggest that searching for genes that correlate with climate could lead to new clues about metabolism related diseases. "The biological processes that influence tolerance to climatic extremes," the authors conclude, "are likely to play important roles in the pathogenesis of common metabolic disorders… Our results argue for a role of climate adaptations in the biological processes underlying the metabolic syndrome and its phenotypes."

This work was funded by The National Institutes of Health.

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Adaptations to climate in candidate genes for common metabolic disorders
Hancock AM, Witonsky DB, Gordon AS, Eshel G, Pritchard JK, et al.
PLoS Genet 4(2): e32.
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Written by Anna Sophia McKenney