Endocrine Abstracts

White adipose tissue is a vital endocrine organ required for the storage of energy in the form of triglycerides, which is released in response to nutrient deprivation, and for the production of hormones such as leptin and adiponectin. In this way, adipose tissue is at the forefront of whole organism energy homeostasis. Adipose tissue dysfunction is associated with many metabolic diseases including T2D, cardiovascular disease and non-alcoholic fatty liver disease (NAFLD). Adipose tissue is rich in mesenchymal stem cells, known as adipocyte precursors, or adipose-derived stem cells. These multipotent cells are responsible for the production of new adipocytes, signaling to existing adipocytes, for the production of chemokines and for response to tissue stress and inflammation. The maintenance of adipose stem cell function is therefore imperative for healthy adipose tissue expansion and homeostasis. Loss of ADSC potency, function and ability to respond correctly to stimuli are emerging hallmarks of metabolic disease. Our work focuses on understanding the mechanisms leading to ADSC dysregulation, using a combination of mouse and human ADSC cell models, paired with primary adipose stem cell cultures obtained from healthy volunteers. In clinic, we derive ADSC cultures from patients undergoing bariatric surgery to better understand these processes in diseased states, and to identify potential targets for pharmaceutical intervention. Our previous work identified AMPK as a regulator of adipocyte cell fate, with exciting consequences including promotion of mitochondrial content and improved insulin sensitivity. We are currently exploring the potential of small molecule AMPK activators in ADSC metabolic regulation, particularly in the suppression of leptin, which will form the basis of this talk.