Scientists say thay have successfully reversed obesity in mice by manipulating the production of an enzyme known as tyrosine-protein kinase-2 (Tyk2). In their experiments, the team at the Virginia Commonwealth University Massey Cancer Center discovered that mice lacking Tyk2 become progressively obese due to aberrant development of Myf5+ brown adipose tissue (BAT), and they claim that this applies to humans as well.
The researchers say the study is the first to provide evidence of the relationship between Tyk2 and brown fat. Previous studies by the team, led by Andrew Larner, M.D., Ph.D., revealed that Tyk2 helps suppress the growth and metastasis of breast cancer, and now the current study suggests this same enzyme could help protect against and even reverse obesity.
Tyk2 RNA levels in BAT and skeletal muscle, which shares a common progenitor with BAT, are dramatically decreased in mice placed on a high-fat diet and in obese humans. The scientists were able to reverse obesity in mice that do not express Tyk2 by expressing a protein known as signal transducer and activator of transcription-3 (Stat3). Stat3 mediates the expression of a variety of genes that regulate a host of cellular processes. Tyk2-negative mice expressing CAStat3 transgene in brown fat also show improved BAT development, normal levels of insulin, and significantly lower body weights. The researchers found that Stat3 formed a complex with a protein known as PR domain containing 16 (PRDM16) to restore the development of BAT and decrease obesity.