Abstract
PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) is defined as the abnormal accumulation of lipids in the liver, called hepatic steatosis, which occurs most often as a concomitant of the metabolic syndrome. Its incidence has surged significantly in recent decades concomitant with the obesity pandemic and increasing consumption of refined carbohydrates and saturated fats. This makes a review of the origins of NAFLD timely and relevant. RECENT FINDINGS: This disorder, which shares histologic markers found in alcoholic fatty liver disease, was named NAFLD to distinguish it from the latter. Recently, however, the term metabolic-associated fatty liver disease (MAFLD) has been suggested as a refinement of NAFLD that should highlight the central, etiologic role of insulin resistance, obesity, and diabetes mellitus. The complexity of the pathways involved in the regulation of hepatic triglyceride synthesis and utilization have become obvious over the past 10 years, including the recent identification of monogenic causes of metabolic-associated fatty liver disease. These include PNPLA3, transmembrane 6 superfamily member 2, GCKR, membrane-bound O-acyltransferase 7 suggest targets for new therapies for hepatic steatosis. SUMMARY: The current review can serve as a guide to the complex pathways involved in the maintenance of hepatic triglyceride levels as well as an introduction to the most recent discoveries, including those of key genes that have provided opportunities for new and novel therapeutics.