Fat stress-induced liver disease is a hepatic manifestation of metabolic syndrome initiated by excess fat
accumulation and encompasses a wide spectrum of diseases from non-alcoholic fatty liver disease to nonalcoholic
steatohepatitis, a precursor lesion progressing to more aggressive liver cirrhosis and hepatocellular
carcinoma. Although the incidence of these fat stress-induced liver diseases is rapidly increasing worldwide in
parallel with the growing epidemics of obesity and metabolic diseases, its exact pathogenesis is not well defined.
Although obesity, sedentary life-style, altered dietary pattern, insulin resistance, altered intestinal barrier function,
inflammatory cytokines, and oxidative stress have been acknowledged as contributing factors because of the
indefinite pathogenesis of metabolic diseases, the only reliable treatment is lifestyle intervention composed of
restrictive diet and exercise. Additionally, some existing medications such as pioglitazone and antioxidants such
as vitamin E were reported to be effective; in this review, several novel agents especifically targeting nonalcoholic
fatty liver disease pathogenesis under clinical trial will be introduced. These include an NPC1L1
blocker (ezetimibe), which significantly improved histological and symptomatic scores associated with steatohepatitis
and fibrosis; clofibrate, phentoxyfylline, ursodeoxycholic acid, and tocopherol, all of which are prescribed
to relieve fat stress; and additional IgY targeted NPC1L1, tocotrienol, ursodeoxycholic acid, and ω-3 polyunsaturated
fatty acids, which are actively under investigation to confirm the safety of long-term use.