Link Found Between Cold Tolerance and Metabolic Syndrome

A new study by researchers at the University of Chicago suggests that there might be a connection between the ability to tolerate cold and metabolic syndrome. The findings have been published in the February issue of the open-access journal PLoS Genetics.

Human populations in colder climates are able to tolerate the weather on account of certain genetic variations. This fact was noted by scientists more than 100 years ago when they found such people to be bulkier and with relatively shorter arms and legs. Studies in the 1950s revealed that colder climates also led to residents having increased body mass index (BMI).

The new study by Anna Di Rienzo and colleagues has now found a connection between climate and many of the genetic variations that are responsible for increasing the risk of metabolic syndrome – a condition that is a cluster of related abnormalities such as obesity, elevated cholesterol levels, heart disease, and diabetes.

The research team selected 82 genes for their study to correlate between the frequency of genetic variations connected with metabolic syndrome and changes in climate variables. Many of the selected genes had already been linked to disease risk. They selected total of 1,034 people from 54 populations from across the world as study participants.

The researchers found extensive correlations between the frequencies of certain genetic variations and colder climates both in terms of latitudes and summer and winter temperatures. Leptin receptor, a gene connected with the regulation of appetite and energy balance was found to have the strongest signals and was highly expressive in colder areas.

This particular gene version is linked to an increased respiratory quotient – the ability to breathe in oxygen and release carbon dioxide. Respiratory quotient is a key factor in heat production. This version of leptin receptor is also associated with lower BMI, less abdominal fat and lower blood pressure, all indicators of lowered risk of metabolic syndrome.

At the same time, the researchers found that certain genes variants responsible for cold tolerance also increased the risk of metabolic syndrome. For example, while some gene variants that increased blood glucose levels could provide protection against the cold by making fuel more readily available for heat production also increased the risk of type 2 diabetes.

One particular version of a gene called FABP2, which is more common in lower temperature climates, was found to increase BMI, promote fat storage and increase cholesterol levels. While the gene variant helped protect against the cold, it also increased the risk of heart disease and diabetes.

“Our earliest human ancestors lived in a hot humid climate that placed a premium on dispersing heat,” said Di Rienzo, professor of human genetics at the University of Chicago. “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 said, “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.”

“All these genes are likely to be involved in metabolic adaptations to cold climates,” added 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.”

According to the researchers, their study might provide additional clues about how metabolism related diseases take hold. “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.”

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