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Tackling Obesity Part 2: Genetics Provides Clues, Not All the Answers 7.06.04 Source: Andrew Schwartz, for CHC exchange As he hunts for genetic clues to obesity, Christian Vaisse works from the basic observation that weight maintenance is about creating a balance between food intake and energy expenditure. Over a period of 25 years, it only takes an imbalance of 16 calories a day to move from normal BMI to extreme obesity. Vaisse's particular interest is in determining when and how such imbalances are tied to genetic mutations. We know that such mutations exist. Researchers discovered the first one by studying overweight mice that failed to secrete leptin, a hormone secreted by fat cells to tell the brain how much fat remains in the body. Without the leptin signal, the body assumes it does not have enough fat and must continue to eat. Subsequently, researchers (including Vaisse) confirmed leptin's role in human weight regulation. A few years later, Vaisse and others identified a mutation in the melanocortin-4 receptor (MC-4R) in the brain's hypothalamus, a receptor that also works to suppress appetite. Mutations in this receptor account for up to 4 percent of cases of extreme obesity, making it the most common obesity gene mutation identified to date. It's an important finding, but it's also notable that mutations that are the primary cause of obesity occur in a very small percentage of people. That's why other genetic research looks at mutations that are not the primary factor, but which indicate a predisposition for obesity in a much larger percentage of obese people. "The additive effect of genes on obesity is about 40 percent," says genetic researcher Wen-Chi Hsueh, who has studied what are known as founder populations, isolated groups that allow researchers to estimate the degree to which genetics affect obesity. Her work is geared towards understanding the gene-environment interaction-essential knowledge for addressing the epidemic. Hsueh believes that further exploration will eventually lead to important advances in treatment and prevention. "In my lifetime, we will do genetic profiles, in much the same way that we do lipid profiles today," she says. (See links to the rest of the six-part article below.) Part 1: Tackling Obesity |
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