Adipocyte-specific amino acid transporters as regulators of insulin sensitivity

• Applicant: Dr. Siegfried Ussar
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 267046495

Obesity and its co-morbidities like cardiovascular disease and type 2 diabetes are a major concern to our health and health care systems. Fundamental to the development of obesity is a misbalance between energy intake and expenditure. Adipose tissue plays a central role in energy homeostasis as white adipose tissue is the primary site of energy storage in form of triglycerides. Conversely, brown adipose tissue wastes energy through mitochondrial uncoupling and thereby enhances energy expenditure. Hence, activation or increase of brown adipose tissue is currently explored as a way to treat or prevent obesity. In addition to the direct consequences of obesity, increased white fat mass strongly correlates with the development of insulin resistance initiating a detrimental chain of events resulting in type 2 diabetes and other diseases of the metabolic syndrome. Adipocyte dysfunction is central to the development of insulin resistance as it results in local and systemic inflammation as well as spill over of lipids from adipose tissue to other organs like the liver and skeletal muscle. Hence, to prevent the onset of obesity induced insulin resistance, novel strategies need to be developed to maintain or restore adipocyte function. A multitude of signaling pathways have been characterized to regulate adipocytes. Among them, amino acids impact on various cellular function and are important modulators of insulin action in these cells. We have identified previously uncharacterized white and brown adipocyte specific amino acid transporters. The key objective of this project is to functionally characterize these brown and white adipocyte specific amino acid transporters in adipose tissue function and to develop reagents targeting these proteins for drug delivery and in vivo imaging. Our experiments will reveal novel insights into the interplay between different cell surface proteins sensing environmental cues to maintain or restore insulin sensitivity in adipose tissue.

• DFG Programme: Research Grants