Gene linked to thinness that resists weight gain identified

Toronto: Researchers have identified a gene linked to thinness that may play a role in resisting weight gain in metabolically healthy but thin people, who account for a small percent of the population.

Using a genetic database of more than 47,000 people in Estonia, the study, published in the journal Cell, found that individuals with certain variations in a gene known as ALK are physically more resistant to weight gain than most.

“We all know these people: it’s around one percent of the population. They can eat whatever they want and be metabolically healthy,” said study senior author Josef Penninger from the University of British Columbia in Canada.

“They eat a lot, they don’t do squats all the time, but they just don’t gain weight,” Penninger added.

For the findings, the research team looked at data from the Estonian Biobank, which includes 47,102 people aged 20 to 44 years old. The team compared the DNA samples and clinical data of healthy thin individuals with normal-weight individuals and discovered genetic variants unique to thin individuals in the ALK gene.

Scientists have known that the ALK gene frequently mutates in various types of cancer, and it gained a reputation as an oncogene, a gene that drives the development of tumors. The role of ALK outside of cancer has remained unclear.

However, this new finding suggested that the gene may play a role as a novel thinness gene involved in weight-gain resistance. The researchers also found that flies and mice without ALK remained thin and were resistant to diet-induced obesity. Furthermore, despite having the same diet and activity levels as normal mice, mice with deleted ALK have lower body weight and body fat.

The team’s mouse studies also suggested that ALK, which is highly expressed in the brain, plays a part thereby instructing the fat tissues to burn more fat from food.

The researchers said that therapeutics targeting the gene might help scientists fight obesity in the future. “If you think about it, it’s realistic that we could shut down ALK and reduce ALK function to see if we did stay skinny,” Penninger said. “ALK inhibitors are used in cancer treatments already. It’s targetable. We could possibly inhibit ALK, and we actually will try to do this in the future,” Penninger added.

Further research will be required to see if these inhibitors are effective for this purpose. The team also plans to further study how neurons that express ALK regulate the brain at a molecular level to balance metabolism and promote thinness.


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