Role of ChREBP in hepatic steatosis and insulin resistance

AbstractNon-alcoholic fatty liver disease is tightly associated with insulin resistance, type 2 diabetes and obesity, but the molecular links between hepatic fat accumulation and insulin resistance are not fully identified. Excessive accumulation of triglycerides (TG) is one the main characteristics of non-alcoholic fatty liver disease and fatty acids utilized for the synthesis of TG in liver are available from the plasma non-esterified fatty acid pool but also from fatty acids newly synthesized through hepatic de novo lipogenesis. Recently, the transcription factor ChREBP (carbohydrate responsive element binding protein) has emerged as a central determinant of lipid synthesis in liver through its transcriptional control of key genes of the lipogenic pathway, including fatty acid synthase and acetyl CoA carboxylase. In this mini-review, we will focus on the importance of ChREBP in the physiopathology of hepatic steatosis and insulin resistance by discussing the physiological and metabolic consequences of ChREBP knockdown in liver of ob/ob mice