Researchers discovered that mice lacking 2 genes, Cnot7 and Tob, remain lean even after eating a high-fat diet.

Scientists examined the fat tissue of these mice and found that the secret of their slender waistlines lies in the increased expression of another gene called Ucp1. Ucp1 helps to reduce fat deposits by converting fat stored in fat cells into heat. It is well known that obese people and obese mice have low concentrations of Ucp1 in their fat cells, so they are prone to store fat rather than burn it off.

The scientists found how Cnot7, Tob, and Ucp1 are functionally related. In order to supply the fat cells with functional Ucp1 protein, the Ucp1 gene has to be transcribed into another molecule called messenger RNA, or mRNA. The stability of Ucp1 mRNA is important to control the total amount of Ucp1 available in the cell, and ultimately, the destiny of stored fat. In obese mice, Cnot7 and Tob degrade Ucp1 mRNA, so that it can no longer be used to make Ucp1 protein.

While previous studies on obesity focused on synthesis of Ucp1 mRNA, this research clarified the mechanism of Ucp1 mRNA degradation. Mice lacking Cnot7 and Tob have more stable Ucp1 mRNA and more Ucp1 protein. Therefore their fat is burned and they do not become obese even on a high-fat diet.

On the other hand, mice and people with unstable Ucp1 mRNA are prone to become fat, since the fat-burning function of Ucp1 is compromised.

http://www.oist.jp/news-center/press-releases/good-news-feast-lovers-obesity-promoting-genes-discovered