Future directions in reducing hepatic lipotoxicity

Abstract

In recent years, the increase in dietary energy availability and sedentary lifestyles has increased the development of obesity. Adipose tissue plays an important role in preventing the accumulation of lipids in other nonadipose tissues. However, during obesity, adipocytes become dysfunctional and, as a consequence, the fatty acids (FA) from adipocytes are released mainly into the liver. In the liver, FA are esterified to form triacylglycerols (TG) and there is also an increase in de novo synthesis of FA due to the hyperinsulinemia present during obesity. As a result, an accumulation of TG in the liver occurs, resulting in hepatic steatosis. Lipotoxicity refers to the FA that exceed the capacity of nonadipose tissues to oxidize them, thus enhancing the metabolic flux of FA to form harmful products involved in the progression of hepatic steatosis to hepatic fibrosis and cirrhosis. As an integral strategy to prevent or treat the consequences of lipotoxicity in humans, healthcare professionals must consider new approaches, including type of diet, risk factors, genetic predisposition, treatment/management and prevention. In recent years, the increase in dietary energy availability and sedentary lifestyles, has further provoked the existing compensatory mecha-nisms that buffer the metabolic consequences of short-term overnutrition, rendering them inca-pable of compensating for chronic changes in energy balance. Subsequently, obesity has become increasingly prevalent. The fact that individuals who are clinically normal show insulin resistance, increased central fat distribution and high plasma triacylglycerols (TG), has prompted calls for the scientific com-munity to elucidate the molecular basis of the consequences of the obesity.