Sanford-Burnham researchers show that protein p62 balances metabolism in fat tissue-making it an attractive target for anti-obesity therapies
In many cases, obesity is caused by more than just overeating and a lack of exercise. Something in the body goes haywire, causing it to store more fat and burn less energy. But what is it? Researchers at Sanford-Burnham Medical Research Institute have a new theory-a protein called p62. According to a study the team published in the Journal of Clinical Investigation, when p62 is missing in fat tissue, the body's metabolic balance shifts-inhibiting "good" brown fat, while favoring "bad" white fat. These findings indicate that p62 might make a promising target for new therapies aimed at curbing obesity.
"Without p62 you're making lots of fat but not burning energy, and the body thinks it needs to store energy," said Jorge Moscat, Ph.D., Sanford-Burnham professor. "It's a double whammy." Moscat led the study with collaborators at Helmholtz Zentrum M-nchen in Germany and the University of Cincinnati.
p62 and obesity
Moscat's team had previously produced mice that completely lack the p62 protein everywhere in their bodies. As a result, the animals were obese. They also had metabolic syndrome. In other words, as compared to mice with p62, mice lacking p62 weighed more, expended less energy, had diabetes and had a hyper-inflammatory response that's characteristic of obesity.
While those results showed that the lack of p62 leads to obesity, "we didn't know which tissue was responsible for these effects, because p62 was missing in all of them," Moscat said.
Some researchers believe that muscle tissue, where energy is expended, controls obesity. Others suspect the liver is a key player, or that the brain's appetite control center is most responsible for obesity.
But then there's fat itself-both white fat and brown fat. White fat is the type we think of as unwanted body fat. Brown fat, on the other hand, is beneficial because it burns calories. Many researchers now believe that brown fat somehow malfunctions in obesity, but the details are unclear.
p62 shifts the balance between white fat and brown fat