"Obesity is often associated with high levels of low-density lipoprotein (LDL) or 'bad' cholesterol, and an increased risk of cardiovascular disease. But the new results, published on 16 October in Nature Medicine, reveal that people with obesity due to relatively rare forms of a gene called MC4R have lower levels of LDL cholesterol and reduced rates of heart disease than do peers with a similar body-mass-index."
""Although the obesity is quite severe in mutation carriers, their risk of these additional complications of obesity is reduced," says Anke Hinney, a geneticist at the University of Duisburg-Essen in Germany, who was not involved with the study. "This is really good news." The results could also point drug developers to new targets for treating high cholesterol, she says. A weighty paradox"
"To learn more, Farooqi and her colleagues turned to MC4R, which encodes a pivotal protein in the brain that acts as a brake on hunger. "Its activation tells you to reduce food intake," she says. "If that doesn't work due to loss-of-function mutations, then you don't have the brake on and you gain weight." As a result, people who carry such mutations are prone to obesity:"
Loss-of-function mutations in MC4R disrupt a brain protein that acts as a brake on hunger, leading to severe obesity through increased food intake. Genetic sequencing of thousands identified hundreds of individuals carrying such mutations, representing about 1% of adults with obesity and up to 5% of children with obesity. People with obesity due to these MC4R mutations display lower LDL cholesterol concentrations and reduced rates of heart disease compared with BMI-matched peers. The paradoxical cardiometabolic profile of mutation carriers highlights MC4R-related pathways as potential targets for therapies to treat high cholesterol.
Read at Nature
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