Jones 2019 MiP2019
Jones JG (2019)
The liver plays a central role in regulating the circulation of fat and glucose during feeding and fasting. Non-alcoholic fatty liver disease (NAFLD), a condition that is now endemic in most Western societies, is characterized by an initial accumulation of triglyceride in hepatocytes. This relatively benign condition can progress to the more severe nonalcoholic steatohepatitis (NASH) and ultimately may lead to cirrhosis or hepatocellular carcinoma.
This lecture will focus on the role that mitochondria play in the initial stages of NAFLD from the perspective of hepatic fatty acid synthesis and oxidation. Since both processes involve the hepatic Krebs cycle, we will review its activity and role in coordinating hepatic carbohydrate and lipid metabolism as well as maintaining the hepatocellular energy state. I will discuss whether mitochondrial substrate metabolism is a driver of NAFLD or if it is responding to increased substrate inflow from outside the liver. I will also review the latest data on how mitochondrial metabolism is altered during the progression of NAFLD.
Finally, and perhaps most importantly, I will try to connect mitochondrial metabolic flux measurements with the more direct assays of mitochondrial function such as membrane potential, oxidative capacity and coupling of electron transport with ATP synthesis. With this approach, I believe it will be possible to associate metabolic flux alterations with specific defects in mitochondrial structure and/or function.
Labels: Pathology: Other
Enzyme: TCA cycle and matrix dehydrogenases Regulation: Fatty acid
- Center Neurosciences, Coimbra Portuguese Diabetes Association, Lisbon, Portugal