Defense Date


Document Type


Degree Name

Master of Science



First Advisor

Andrew Larner


Obesity results from an excess of adipose tissue and is a major risk factor for type 2 diabetes, cardiovascular disease, and cancer. Adipose tissue exists in two main forms: white adipose tissue (WAT), which stores energy as triglycerides, and brown adipose tissue (BAT), which dissipates stored energy as heat. White adipose tissue is composed of several subcutaneous and visceral depots, each possessing distinct molecular and functional characteristics. Brown-like adipocytes can emerge in WAT depots in response to cold or beta-adrenergic stimulation. These cells have been called “beige” or “brite” (brown-in-white) cells. The reduction of obesity in mice treated with beta-adrenergic agonists is correlated with the emergence of beige cells. Beige cell development occurs most readily in subcutaneous depots, and to the least extent in visceral depots. Understanding the molecular mechanisms underlying beige cell development in different WAT depots may be important in discovering new therapies against obesity and related diseases. Our lab has previously discovered that Tyrosine Kinase 2 (Tyk2), an important mediator of cytokine signaling, promotes the development of classical brown adipose tissue. Due to the lack of functional BAT, Tyk2-knockout (Tyk2-/-) mice become grossly obese with age and develop several symptoms of the metabolic syndrome. In the present study, we have found a potential role of Tyk2 in the development of beige cells. Here, we show that mRNA expression of BAT-selective genes (UCP1, Cidea, Cox8b, and Elovl3) is significantly reduced in subcutaneous WAT of Tyk2-knockout (Tyk2-/-) mice compared to wild-type mice. Surprisingly, BAT-selective genes are induced in Tyk2-/- subcutaneous WAT by acute starvation. These findings suggest that Tyk2 is required for the development of beige cells under ambient conditions, and that the need for Tyk2 in beige cell development is bypassed during nutritional stress, a stimulus of the sympathetic response.


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Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

July 2011