Journal Club: Metabolism/Cell Biology

Contributor
Graduate Division

Presentation: “Tyk Talk: Better Understanding Brown Adipose Tissue Differentiation”

Presenter: Alex Samocha (first-year Biomedical Sciences student)

Paper: Derecka, M. et al. “Tyk2 and stat3 regulate brown adipose tissue differentiation and obesity. Cell Metab. 2012 Dec 5;16(6):814-24.

In a nutshell:

Authorities view obesity as one of the most serious public health issues of the modern world. Obesity increases the likelihood of such diseases as Type 2 diabetes, osteoarthritis, heart disease and some types of cancer.  

In the United States, the past few decades have seen an astronomical rise in the epidemic, stemming primarily from increasingly sedentary lifestyles and the availability of unhealthy processed foods. Because advising people to lead healthier lifestyles hasn’t been wholly effective, scientists are also turning to metabolic studies to combat this problem.

We know that obesity arises from an energy imbalance — if caloric intake exceeds expenditure, people (and mice) will probably gain weight.  This imbalance may be observed on a cellular level, such as when energy-storing white fat exceeds energy-dissipating brown fat.  

The authors of this paper found that the protein Tyk2 is important in regulating this balance.  A lack of Tyk2 is associated with obesity and decreased energy expenditure in both mice and humans. 

This may be because Tyk2 appears to <pls check edit>regulate the differentiation of brown fat.  For example, Tyk2-deficient mice were unable to shiver (a function of brown adipose tissue or BAT) in response to cold. 

Furthermore, genetic rescue of Tyk2 deficiency led to improved BAT development, insulin levels and body weight.  At present, gene therapy is an unlikely treatment for obesity, but these studies provide insight into its molecular basis. 

Interestingly, Tyk2 is also involved in inflammation, suggesting another link between metabolism and immunity — not surprising given the latest research on how exercise can help ward off infections.  The moral of the story: Stay active and keep your Tyk2 intact.