Obese people who are trying to lose weight and keep it off face many challenges when it comes to their diet and exercise. Hormone imbalances, such as lower levels of the hormone leptin, mean that obese people have to eat more to feel full. On top of that, many of them have difficulty getting into an exercise routine because of their limited mobility. It seems like obese people may have one other challenge to face, since a new study found that the a mutated gene could be causing increased hunger and a slower metabolism. 

Researchers looked at 2,101 adult patients with severe early-onset obesity and found that about one percent of them had a mutated version of the gene KSR2. Compared to patients who had normal variances of the gene, those with the mutation showed an increased appetite during childhood (hyperphagia), a lower heart rate, reduced basal metabolic rate, and severe insulin resistance. Additionally, they found that about two percent of children who were obese by 5 years old would have the gene.  

“You would be hungry and wanting to eat a lot. You would not want to move because of a slower metabolism and would probably also develop type 2 diabetes at a young age,” Sadaf Farooqi, lead researcher of the study and professor of metabolism and medicine at Cambridge University, told the BBC. “It slows the ability to burn calories and that’s important as it’s a new explanation for obesity.”

KSR2 was previously found to play a role in energy balance and metabolism during studies on mice, according to a press release. The gene is primarily active in the brain where it manages the way individual cells decode signals. Experiments in cells showed that the mutations impaired glucose and fatty acid oxidation. But the researchers also found a simple solution: the diabetes drug metformin fixed these low levels of fatty acid oxidation.

“This work adds to a growing body of evidence that genes play a major role in influencing a person’s weight and may be useful for developing new way to treat people who are heavy and develop diabetes,” Farooqi said in the statement.

About 17 percent of American children and adolescents, ages 2-19, are considered obese, according to the Centers for Disease Control and Prevention. Childhood obesity nearly tripled since 1980, but has seen a slight decline in recent years, as children are becoming more physically active and eating healthier. Obese children are more likely to keep the weight into adulthood, but their obesity-related health risks start early. One study has shown that 70 percent of obese children have at least one risk factor for cardiovascular disease, and 39 percent have two or more.

 

Source: Pearce L, Farooqi S, Barroso I, et al. KSR2 Mutations Are Associated with Obesity, Insulin Resistance, and Impaired Cellular Fuel Oxidation. Cell. 2013.