Scientists Identify Gene that Causes Obesity in Mice

U.S. genetic researchers led by Prof James McManaman from the University of Colorado’s School of Medicine have found that deleting a gene called Perilipin 2 (Plin2) in mice prevents them from becoming obese even on a high fat diet.

Obese and thin mice (Shannon Reilly / University of Michigan)

Obese and thin mice (Shannon Reilly / University of Michigan)

“When fed a diet that induces obesity these mice don’t get fat. It may be possible to duplicate this in humans using existing technology that targets this specific gene,” Prof McManaman said.

The team created a strain of mice without the Plin2 gene which produces a protein that regulates fat storage and metabolism. They immediately found that the mice were resistant to obesity.

Usually, mice fed a high fat diet will eat voraciously, yet these showed an unusual restraint. Not only did they eat less, they were more active.

Their fat cells were also 20 percent smaller than typical mice and did not show the kind of inflammation usually associated with obesity, the study said. Obesity-associated fatty liver disease, common in obese humans and rodents, was absent in the mice without the Plin2 gene.

“The mice were healthier,” Prof McManaman said. “They had lower triglyceride levels, they were more insulin-sensitive, they had no incidents of fatty liver disease and there was less inflammation in the fat cells.”

“The absence of the gene may cause fat to be metabolized faster.”

Prof McManaman and colleagues report their findings in the Journal of Lipid Research.

“Now we want to know why this works physiologically,” the scientist said. “We want to better understand how this affects food consumption.”

According to the study, understanding how Plin2 is involved in the control of energy balance will provide new insights into the mechanisms by which nutrition overload is detected, and how individuals adapt to, or fail to adapt to, dietary challenges.

The consequences for people are highly significant since they also possess the Plin2 gene.

“It could mean that we have finally discovered a way to disrupt obesity in humans,” Prof McManaman said. “That would be a major breakthrough.”

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Bibliographic information: McManaman JL et al. Perilipin-2 Null Mice are Protected Against Diet-Induced Obesity, Adipose Inflammation and Fatty Liver Disease. The Journal of Lipid Research, published online on February 12, 2013; doi: 10.1194/jlr.M035063