2014 Early Career Award: Dr. Alexander Bartlelt

DR. ALEXANDER BARTELT

2014 Early Career Award Recipient
Brown Fat in the Center of Metabolic Health

Short Bio

Dr. Alexander Bartelt is currently a Postdoctoral Research Fellow at the Department of Genetics and Complex Diseases, Harvard School of Public Health in Boston, MA, USA. His research is dedicated to understanding the molecular basics of lipid and lipoprotein metabolism and related pathologies such as obesity, atherosclerosis and osteoporosis. He received his Diploma in Biochemistry and Molecular Cell Biology from University of Hamburg, Germany in 2007 with honors. During his PhD at University Medical Center Hamburg-Eppendorf he pioneered brown adipose tissue metabolic research with Prof. Joerg Heeren. Dr. Bartelt is also interested in the relationship of lipid and bone metabolism. In his postdoctoral studies he investigates metabolic adaptations of adipose tissue in extreme conditions such as cold or obesity. Dr. Bartelt’s contributions to the general understanding of systemic nutrient homeostasis have been recognized by national and international awards, fellowships and honors. His work has been funded by the Schering Foundation, the European Atherosclerosis Society and the German Research Foundation DFG.

 

Abstract

 

Whereas white adipose tissue (WAT) serves mainly as an energy reservoir and endocrine organ, brown adipose tissue (BAT) is able to dissipate high-caloric nutrients such as carbohydrates and fatty acids to produce heat in order to defend the body against cold. Until 2011, the mechanistic details of fatty acid delivery as fuels for BAT thermogenesis were insufficiently understood. Moreover, the detailed contribution of BAT to systemic metabolism in terms of lipid and glucose homeostasis was not known. In a series of in vivo experiments, combining classical radioactive fatty acid tracer studies with state-of-the-art nanocrystal-based lipoprotein imaging techniques, we were able to demonstrate that BAT in quantitative terms controls plasma triglyceride and glucose metabolism. Activating BAT by overnight cold exposure reduced plasma triglyceride levels drastically, even in postprandial conditions. Furthermore, we identified a novel lipoprotein pathway involving lipolysis by lipoprotein lipase (LPL) and fatty acid uptake by CD36 into brown adipocytes. BAT consumed nearly as much as 50% of a meal in obese and lean animals, ameliorating glucose intolerance and insulin resistance. Beyond dissipating nutrients, BAT activation and also stimulating adipose tissue “browning” has a profound impact on systemic fatty acid fluxes and cholesterol homeostasis. BAT possesses high capacity for de novo lipogenesis, producing significant amounts of monounsaturated fatty acids. We were able to show that BAT-derived fatty acids can be used as markers of HDL turnover along with the discovery that BAT modulates HDL metabolism to facilitate cholesterol excretion. Our studies place BAT in the center of metabolic health, carrying great therapeutic potential for fighting obesity, insulin resistance and atherosclerosis.