Principal Investigator: Donald B. Jump, Ph.D.
The type and quantity of dietary fat ingested affects human health, particularly the onset and progression of chronic diseases like diabetes, obesity, metabolic syndrome, and atherosclerosis. The liver plays a central role in whole-body carbohydrate and lipid metabolism. Our research focuses on defining mechanisms for fatty acid regulation of hepatic carbohydrate and lipid metabolism.
Our research has assessed the role hepatic fatty acid synthesis plays in the control of complications linked to type 2 diabetes mellitus (T2DM) and obesity, particularly hyperglycemia and fatty liver disease. Hepatic lipid synthesis, including the synthesis of saturated and mono- and polyunsaturated fatty acids, is significantly altered in humans with T2DM, obesity, and metabolic syndrome. Our studies have identified a novel connection between enzymes involved in monounsaturated and polyunsaturated fatty acid synthesis and the control of hepatic glucose production and liver fat content. While these studies clarify molecular interactions between different metabolic pathways, they may also identify possible novel approaches to control certain diabetic complications.
Other research in my laboratory has assessed the capacity of dietary omega-3 fatty acid supplementation to control high-fat, diet-induced, non-alcoholic fatty liver disease (NAFLD). The incidence of NAFLD closely parallels the incidence of obesity in the U.S. population. NAFLD is a spectrum of diseases that span simple fatty liver (benign steatosis) to non-alcoholic steatohepatitis (NASH). NASH is characterized as fatty liver with inflammation, fibrosis, oxidative stress, and hepatic damage. If left unchecked, NASH can progress to cirrhosis and liver cancer. Our recent studies have established that dietary omega-3 fatty acids found in fish oil (eicosapentaenoic acid and docosahexaenoic acid) can be used at clinically relevant levels of intake to attenuate multiple markers of NASH (hepatosteatosis, inflammation, and fibrosis) in a mouse model of high-fat, diet-induced NASH. Future studies will determine whether specific omega-3 fatty acids, either alone or in combination with other treatments, can be used in therapy to reduce hepatic damage associated with obesity-linked NASH.