Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma: Implications for Lycopene Intervention

Abstract

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 hepatic carcinogenesis. Lycopene is a non-provitamin A carotenoid and the pigment principally responsible for the characteristic deep-red color of ripe tomato and tomato products, as well as some fruits and vegetables. Lycopene’s innate antioxidant and anti-inflammatory properties have generated research interests on its capacity to protect against human diseases that are associated with oxidative stress and inflammation. In addition, differential mechanisms of lycopene metabolism including endogenous cleavage by carotenoid cleavage oxygenases (BCOs), generate lycopene metabolites that may also have significant impact on human disease development. However, it remains to be elucidated as to whether lycopene or its metabolites apolycopenoids have protective effects against obesity-related complications including inflammation and tumorigenesis. This article summarizes the in vivo experiments that elucidated molecular mechanisms associated with obesity-related hepatic inflammation and carcinogenesis. This review also provides an overview of lycopene metabolism, and the molecular pathways involved in the potential beneficial properties of lycopene and apolycopenoids. More research is clearly needed to fully unravel the importance of BCOs in tomato carotenoid metabolism and the consequence on human health and diseases.

Lycopene and Apo-10′-lycopenoic Acid Have Differential Mechanisms of Protection against Hepatic Steatosis in β-Carotene-9′,10′-oxygenase Knockout Male Mice

“…Lycopene can accumulate in adipose tissue (10) and modulate adipose lipid/inflammationassociated signaling cascades (41,42). Evidence showed that the portal vein directly connects the liver with the visceral MAT (43,44), and visceral fat content is highly correlated with the degree of liver steatosis in humans (45,46).…”

“…In vivo and in vitro studies have suggested that lycopene may use multifaceted mechanisms to reduce CVD and NAFLD risks (8)(9)(10), mechanisms that include modulating cholesterol metabolism, serving as an antioxidant, and inhibiting inflammation (8)(9)(10). Of note, NAFLD patients have substantially reduced plasma lycopene concentration (11), suggesting potential interactions between low lycopene status and CVD risk.…”

Mediterranean Diet and Healthy Ageing: A Sicilian Perspective

“…Table 1 reports a brief description of some foods characterizing Sicilian countryside dietary habits [27,28,29,30,31,32]. As previously stated, olive oil plays a central role in MedDiet [2,11,33,34,35] and a glass of wine with meals may be assumed every day [2,11].…”

Lycopene Attenuates Colistin-Induced Nephrotoxicity in Mice via Activation of the Nrf2/HO-1 Pathway

“…Lycopene has been shown to activate the Nrf2/ HO-1 pathway and can protect against nephrotoxicity induced by gentamicin, adriamycin, and cisplatin (28,31,(36)(37)(38)(39). Lycopene displays antioxidant and anti-inflammatory effects; in one clinical trial, the data suggested that it may play an important role in protection against various chronic diseases (e.g., cancer) (40). In the present study, we investigated the nephroprotective effect of lycopene on polymyxin-induced nephrotoxicity and the involvement of the Nrf2/HO-1 pathway in a mouse model.…”