Molecular links between insulin resistance, NAFLD and dyslipidemia
Non-alcoholic fatty liver disease (NAFLD) is a chronic, progressive condition that is widely considered to be the hepatic manifestation of the metabolic syndrome. The primary feature of NAFLD is the accumulation of triglycerides in the liver, called steatosis. Chronically, steatosis can lead to hepatocyte dysfunction and inflammation, called non-alcoholic steatohepatitis (NASH). Obesity and insulin resistance are major risk factors for NAFLD and can also drive metabolic changes which may exacerbate steatosis and inflammation. Atherogenic dyslipidemia is a common comorbidity of NAFLD and cardiovascular disease is among the most common causes of death in these patients. In this presentation, I will briefly review the pathophysiology of NAFLD, focusing on the role of insulin resistance. I will finish by highlighting changes in hepatic transcriptome from a large cross-sectional NAFLD that may help explain the development of atherogenic dyslipidemia in these subjects.
Joel Haas is a Group Leader in the Laboratory INSERM UMR1011 Nuclear Receptors, Metabolic and Cardiovascular Diseases, in Lille, France. Prior to this, he completed a post-doctoral fellowship (2013-2019) with Dr. Bart Staels focusing on the interactions between inflammation and metabolism in NAFLD. He completed his PhD training at the University of California-San Francisco studying the differing cellular roles of the triglyceride synthesis enzymes DGAT1 and DGAT2. His group studies the pathophysiology of NAFLD focusing on the molecular alterations in hepatic lipid and amino acid metabolism and activation of the hepatic immune system in the transition from steatosis to NASH.