β-cryptoxanthin and fatty liver disease: new insights

HepatoBiliary Surg Nutr 2023;12(3):450-452 | https://dx.doi.org/10.21037/hbsn-23-201 β-cryptoxanthin is a nutritionally important xanthophyll found in orange-fleshed tropical and citrus fruits, including papaya, oranges, and tangerines (1). It is also one of the most commonly detected carotenoids in human tissues (1). Uniquely, β-cryptoxanthin is the only regularly consumed dietary xanthophyll to have an intact β-ionone ring, thus in addition to functioning as an antioxidant it can also be metabolized to vitamin A. A limited number of past studies have shown a beneficial effect of β-cryptoxanthin supplementation in animal models of hepatic steatosis (2). As discussed below, the recent publication by Liu et al. from the group led by Dr. Xiang-Dong Wang has provided new insight into the benefits of β-cryptoxanthin supplementation in the context of fatty liver disease (3). Epidemiologica l data and animal s tudies have suggested that high dietary carotenoid intake, including β-cryptoxanthin, may have beneficial health effects on hepatic fat accumulation (2,3). As discussed elsewhere, there are multiple possible mechanisms through which β-cryptoxanthin exerts its beneficial effect, this includes the molecule acting as an antioxidant, or undergoing oxidative cleavage to produce vitamin A or bioactive apocarotenoids (2). Regarding its cleavage, the two major carotenoid cleavage enzymes that can metabolize β-cryptoxanthin are BCO1 (β-carotene-15,15'-oxygenase), which generates vitamin A, and BCO2 (β-carotene-9',10'-oxygenase), which generates apocarotenoids (2,3). In this context, there is a gap in our knowledge regarding the mechanism underlying β-cryptoxanthin’s beneficial effects, and whether cleavage by BCO1 and/or BCO2 is required to mediate these effects. Indeed, past studies in rodent models of non-alcoholic fatty liver disease have demonstrated a protective effect of β-cryptoxanthin supplementation on markers of hepatic fat accumulation and inflammation (4-6). Despite their positive results, these studies did not shed light on whether these effects were dependent on β-cryptoxanthin metabolism by BCO1/2. In two separate studies, also from the group of Dr. Wang, the effect of β-cryptoxanthin supplementation was studied in a mouse model consuming a diet high in refined carbohydrates (7,8). The importance of β-cryptoxanthin cleavage was genetically dissected in these studies through the use of Bco1/Bco2 double knockout mice. Both studies showed that β-cryptoxanthin supplementation inhibited hepatic lipid accumulation, inflammation and hepatocellular carcinoma progression. Moreover, this effect was independent of Bco1/Bco2 genotype, suggesting that these positive effects were mediated by intact β-cryptoxanthin and occurred independently of its cleavage by BCO1/2 (7,8). As Editorial