What Mice Can Tell Us About Obesity and Genetics

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While our eating habits certainly play a role in how much we weigh, our rodent cousins confirm that some of our risk for obesity is written in our genes.

For over two years, the researchers at the University of California, Los Angeles, studied the effect of high-fat and high-sugar diets on more than 100 genetic strains of laboratory mice. As they monitored weight gain among the furry creatures, the scientists identified 11 genetic regions associated with obesity and the deposition of fat from the diet — several of which overlapped with genes that have been linked to obesity in humans.

At the start of the study, the mice consumed a normal diet for eight weeks, followed by either a high-fat (which resembled fast-food fare for people) or high-sugar diet for an additional eight weeks. The researchers dutifully recorded changes in the animals‘ fat deposition throughout the second eight weeks and found that the among of fat that built up varied widely among the different genetic strains; the mice added anywhere from 0% to over 600% of body fat compared with their original fat measurements.

(MORE: Childhood Obesity: Scientists Find Two Gene Variants that Predispose Kids to Weight Gain)

The scientists then connected the amount of fat gained with changes in the animals’ gene activity and found that about 80% of body fat is likely regulated by the genes, which suggests that the processing of the food the mice ate was strongly directed by DNA. That conclusion was supported by the fact that the total amount of food the animals ate was not related to how much body fat they gained. The mice that ate the most did not necessarily gain the most weight.

“People generally assume that obese people eat a lot, but it was surprising that the weight gain wasn’t determined by the amount of fast food that was consumed,” says the study’s principal investigator Jake Lusis, a professor of medicine and human genetics and of microbiology, immunology and molecular genetics at the Geffen School of Medicine at UCLA.

Although the researchers say that eating sugary and fatty foods can pack on the pounds, they found that physical activity and energy expenditure were also important — the idea that in order to lose or maintain weight, you have to burn off as many calories as you consume. “Our study suggests that what’s more important is their physical activity, how much the mice move and how some metabolize food. Some are more efficient at taking calories and putting them into fat, rather than just spending it as energy. In the case of the mice, it looks like the metabolism and activity is way more important than the amount of food consumed,” says Lusis.

(MORE: Doctors Should Screen All Adults for Obesity, U.S. Panel Says)

And that may be true for people as well. Previous studies have estimated that anywhere from 50% to 90% of obesity is inherited in the genes, but so far genetic analyses have only identified about 3% of these contributions. In addition, it’s also likely that genes may not be directly responsible for obesity, but only be co-opted in the presence of certain environmental influences, like stress. Either way, teasing apart the different ways that DNA may impact weight could lead to improved ways of combating obesity. “If we are able to identify these genes and understand what pathways they control, then I think this has major implications in terms of diagnosis and more importantly in terms of developing therapies [for people],” says Lusis.

So he and his colleagues plan to test the gene regions they identified in the mice in various laboratory environments to gain a better understanding of how they influence body fat and even behavioral and neurological responses, such as appetite and hunger signals, under different conditions. “Genes don’t act individually, they act by affecting other genes and interacting with the environment. If we can understand the full picture, it could potentially be really important for the critical problem of obesity,” says Lusis.

The study is published in the journal Cell Metabolism.