Omega-3 Polyunsaturated Fatty Acids for Treatment of Nonalcoholic Fatty Liver Disease: A Possible Case for Personalized Therapy

Abstract

In a recent issue of PLOSone Depner et al. [1] reported an excellent study on omega-3 fatty acid-induced changes in lipid metabolomics that may be involved in attenuating western diet-induced nonalcoholic steatohepatitis (NASH). A western diet, which is typically rich in saturated and trans fats, that leads to fat accumulation in the liver. This condition resembles alcoholic fatty liver disease; however, it progresses in the absence of any alcohol intake and is known as nonalcoholic fatty liver disease (NAFLD) [2]. In most individuals, the liver is devoid of any symptoms or problems that will only culminate in mild steatosis. However, in some cases, especially individuals with obesity and metabolic syndrome, the fat accumulation is accompanied with inflammation and causes NASH. If untreated, NASH worsens and causes fibrosis resulting in scarring of the liver. The pathophysiologic pathway of NAFLD is not clearly elucidated. Day and James [3] in 1998 proposed the “two-hit phenomenon,” where the “first hit” consists of triglyceride (TG) depositions in hepatocytes causing cellular dysfunction and death (lipotoxicity). The hyperinsulinemia and insulin resistance play a role in the first hit causing an alteration in uptake, synthesis, degradation, and secretion of free fatty acids leading to an accumulation of fat in hepatocytes, or steatosis [4,5]. Steatosis by itself is not detrimental, but the steatotic liver becomes more vulnerable to “second hits” by inflammatory cytokines, endotoxins, and oxidative stress causing mitochondrial dysfunction, which ultimately results in hepatocyte injury and fibrosis [6]. NAFLD is also associated with an increased risk of cardiovascular disease (CVD). To date there is no standardized optimal treatment, although several approaches to treat NAFLD have been adopted, including weight reduction, limiting dietary carbohydrate intake, inhibiting fat absorption by sibtramine and orlistat, lowering lipid profile by statins, improving insulin sensitivity by Metformin and thioglitazone and reducing oxidative stress by vitamin E [7-9].