Evaluation of liver secreted proteins identifies novel regulators of glucose metabolism

Watt MJ and Montgomery MK

Department of Physiology, University of Melbourne, Melbourne, 3010.

Obesity is a risk factor for the development of inter-related complications including dyslipidemia, non-alcoholic fatty liver disease (NALFD), cardiovascular disease and type 2 diabetes. An accumulation of lipid in the liver, which is clinically known as hepatic steatosis, is a pathologic abnormality that is common in obese and type 2 diabetes patients. Hepatic steatosis occurs when fatty acid supply outweighs fatty acid demand and occurs in a time-course that usually precedes the induction insulin resistance and type 2 diabetes. This presentation describes our laboratories use of proteomics to evaluate how ’heptokine’ secretion is altered in murine models of NAFLD and non-alcoholic steatohepatitis. We report on the pre-clinical validation of several liver secreted factors that either cause insulin resistance and disturbances in systemic metabolic homeostasis or enhance glycemic control in diabetes. These studies have unravelled previously appreciated biology and pave the way for potential therapeutic intervention for type 2 diabetes.