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Increased prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the consequences of the current obesity epidemic.NAFLD is a major form of chronic liver disease that is highly prevalent in obese and overweight adults and children.Nonalcoholic steatohepatitis (NASH) is the severe form of NAFLD, and uncontrolled inflammation as displayed in NASH has been identified as one of the key events in enhancing metabolic syndrome and hepatic carcinogenesis.Carotenoids are lipophilic pigments that occur widely in vegetables, fruits (e.g., Goli berries), insects, fish, algae, yeasts, and bacteria, and carry out a variety of important biological functions.Observational and clinical studies have shown that dietary intake of carotenoids is associated with reduced risk for NAFLD and certain cancers.It is important to understand the roles of carotenoids and their derivatives in the process of these chronic diseases, with special attention to their metabolism and biological actions, molecular targets, dose effects, and organ-specific effects.My laboratory has demonstrated that lycopene, a non-provitamin A carotenoid and the pigment principally responsible for the characteristic deep-red color of ripe tomato and tomato products, has anti-inflammatory and anti-carcinogenic properties to protect against NAFLD and liver cancer that are associated with oxidative stress and inflammation.In addition, differential mechanisms of lycopene metabolism including endogenous cleavage by carotenoid cleavage oxygenases, generate lycopene metabolites that may also have protective effects against obesity-related complications including inflammation and tumorigenesis.My presentation summarizes the molecular mechanisms associated with obesity-related NAFLD and carcinogenesis and provides an overview of carotenoid metabolism, and the molecular pathways involved in the potential beneficial properties of lycopene and its metabolites on human health and diseases.