Two Proteins Stop Mice Getting Fat

Further evidence for this idea is now provided by researchers from McGill University, Canada, who show that mice lacking two proteins known to be effectors of some mTOR functions (4E-BP1 and 4E-BP2) are more obese than normal mice.

In their study, which appears in the February issue of the Journal of Clinical Investigation, Nahum Sonenberg and colleagues show that mice lacking both 4E-BP1 and 4E-BP2, when fed either a normal or high-fat diet, weigh more than wild-type mice. The increased weight gain after being on a high-fat diet was a result of increased fat accumulation, associated with decreased energy expenditure, decreased fat degradation, increased differentiation of fat cells, and increased insulin resistance (one of the main triggers of type 2 diabetes and a contributing factor to the metabolic syndrome).

This study indicates that two effectors of mTOR functions are crucial for preventing mice from becoming obese and suggests that 4E-BP1 and 4E-BP2 might provide therapeutic targets for the treatment of obesity and the metabolic syndrome.

In an accompanying commentary, Liangyou Rui from the University of Michigan Medical School, Ann Arbor, puts these observations into the bigger picture of how other mTOR effectors also affect body weight and how this pathway intersects with other molecules known to regulate obesity.