p62 shifts the balance between white fat and brown fat
In their latest study, Moscat and colleagues set out to pinpoint the specific tissue responsible for obesity when p62 is missing. They made several different mouse models, each missing p62 in just one specific organ system, such as the central nervous system, the liver, or muscle. In every case, the mice were normal. They weren't obese like the mice lacking p62 everywhere.
Then they made a mouse model lacking p62 only in their fat tissue. These mice were obese, just like the mice missing p62 in all tissues. Upon further study, the researchers found that p62 blocks the action of an enzyme called ERK while activating another enzyme called p38. When p62 is missing, the enzyme p38 is less active in brown fat, while ERK is more active in white fat. As a result, Moscat said, p62 is "a master regulator" in normal fat metabolism.
According to Moscat, the discovery of p62's role in brown fat tissue is encouraging, because fat tissue is much more accessible than other parts of the bodythe brain, for examplefor potential drug therapies. "This makes it easier to think about new strategies to control obesity," he said.
New methods for preventing or treating obesity, a major epidemic in the United States, are urgently needed. Drug therapies designed to minimize the intake of food have had limited success and also produce considerable side effects.
|Contact: Heather Buschman, Ph.D.|
Sanford-Burnham Medical Research Institute