Inflammatory Control of Brown Fat Function

• Applicant: Professor Dr. Alexander Bartelt
• Subject Area: Endocrinology, Diabetology, Metabolism ; Gastroenterology
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 236148629

Whereas white adipose tissue serves mainly as an energy reservoir, brown adipose tissue is able to dissipate carbohydrates and fatty acids to produce heat in order to defend the body against cold. Therefore stimulating brown adipose tissue activity could be a promising strategy to facilitate weight loss in obese people. An important short-coming of this concept is the fact that obese and elder people are characterized by reduced brown adipose tissue activity. One possible mechanism leading to this decline is chronic inflammatory stress: In human obesity the storing capacity of white adipocytes is overwhelmed leading to a low-grade, chronic inflammatory response that further worsens metabolic dysfunction. It is well accepted that cellular networks linking inflammation and endoplasmic reticulum stress are important contributors to white adipocyte dysfunction. However, it is unclear whether also brown adipocytes and thus their ability to protect the body from excess lipid accumulation are disturbed by obesity-associated inflammatory stress. The aim of my proposal is to characterize the effects of obesity and insulin resistance on brown adipose tissue inflammation and endoplasmic reticulum stress in mice. Moreover, molecular mechanisms by which inflammation and endoplasmic reticulum stress impact on brown adipocyte function will be investigated in primary mouse brown adipocytes. Finally, I will investigate if protecting brown adipocytes from inflammation and endoplasmic reticulum stress using transgenic mouse models could attenuate or even prevent obesity and metabolic disease. The outcome of the proposal might point to new avenues to sustain brown adipose tissue activity in obesity, thus eventually treating or preventing metabolic disease in humans.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Gokhan Hotamisligil, Ph.D.