Figure 2: Summary of insulin resistance-induced lipid abnormalities and consequent pathogenesis of NAFLD. In an insulin resistant setting, insulin is unable to inhibit lipolysis in adipose tissue leading to overflow of free FA into the bloodstream and in the liver. In the liver, hyperinsulinemia and hyperglycemia induce the synthesis of fatty acid and cholesterol which results in increased triglyceride synthesis and VLDL assembly and secretion. Since triglyceride synthesis prevails over VLDL secretion, excess triglycerides accumulate and lead to fatty liver development. In NASH, triglyceride synthesis and VLDL assembly is impaired and free FA and cholesterol accumulate. Increased lipid accumulation leads to lipid peroxidation and inflammation which exacerbates liver damage.