Astaxanthin lowers plasma TAG concentrations and increases hepatic antioxidant gene expression in diet-induced obesity mice

Abstract

Non-alcoholic fatty liver disease (NAFLD) is significantly associated with hyperlipidaemia and oxidative stress. We have previously reported that astaxanthin (ASTX), a xanthophyll carotenoid, lowers plasma total cholesterol and TAG concentrations in apoE knockout mice. To investigate whether ASTX supplementation can prevent the development of NAFLD in obesity, male C57BL/6J mice (n 8 per group) were fed a high-fat diet (35 %, w/w) supplemented with 0, 0·003, 0·01 or 0·03 % of ASTX (w/w) for 12 weeks. The 0·03 % ASTXsupplemented group, but not the other groups, exhibited a significant decrease in plasma TAG concentrations, suggesting that ASTX at a 0·03 % supplementation dosage exerts a hypotriacylglycerolaemic effect. Although there was an increase in the mRNA expression of fatty acid synthase and diglyceride acyltransferase 2, the mRNA levels of acyl-CoA oxidase 1, a critical enzyme in peroxisomal fatty acid b-oxidation, exhibited an increase in the 0·03 % ASTX-supplemented group. There was a decrease in plasma alanine transaminase (ALT) and aspartate transaminase (AST) concentrations in the 0·03 % ASTX-supplemented group. There was a significant increase in the hepatic mRNA expression of nuclear factor erythroid 2-related factor 2 and its downstream genes, which are critical for endogenous antioxidant mechanism, in the 0·03 % ASTX-supplemented group. Furthermore, there was a significant decrease in the mRNA abundance of IL-6 in the primary splenocytes isolated from the 0·03 % ASTX-supplemented group upon lipopolysaccharide (LPS) stimulation when compared with that in the splenocytes isolated from the control group. In conclusion, ASTX supplementation lowered the plasma concentrations of TAG, ALT and AST, increased the hepatic expression of endogenous antioxidant genes, and rendered splenocytes less sensitive to LPS stimulation. Therefore, ASTX may prevent obesity-associated metabolic disturbances and inflammation.

The Potential of Non-Provitamin A Carotenoids for the Prevention and Treatment of Non-Alcoholic Fatty Liver Disease

“…This pigment is responsible for the characteristic pink and red color of seafood such as salmon, trout, shrimp, lobster, and fish eggs [37]. Due to its long chain with conjugated double bonds and keto (C=O) moieties on each ionone ring, astaxanthin is a potent antioxidant that scavenges mostly peroxyl radicals, protecting fatty acids and biological membranes against lipid peroxidation [37,38,39]. For this reason, the potential of this carotenoid in ameliorating oxidative stress-induced diseases such as NAFLD has been studied [36].…”

“…The results showed that incubation with astaxanthin, but not α-tocopherol, resulted in a dose-dependent decrease in TG accumulation in primary hepatocytes. The mechanism by which astaxanthin decreased lipid accumulation in hepatocytes is suggested to be a reduction in fatty acid uptake as shown by a dose-dependent decrease in expression of cluster of differentiation 36 (CD36) with astaxanthin [38]. …”

“…Another experiment was conducted to evaluate the appropriate dose of astaxanthin to prevent NASH in mice [38]. C57BL/6J mice were fed six different diets for 12 weeks: normal chow, chow containing 0.0067% or 0.02% astaxanthin, high-fat, high-cholesterol, and cholate diet, or high-fat, high-cholesterol diet with 0.0067% or 0.02% astaxanthin.…”

Astaxanthin as a Potential Protector of Liver Function: A Review

“…Astaxanthin also inhibits the conversion of xanthine dehydrogenase to xanthine oxidase and the protein carbonyl level in rat liver tissues following ischemia-reperfusion injury (a severe oxidative condition) [16]. Astaxanthin has also been shown to induce expression of nuclear factor-erythroid 2-related factor 2 mRNA and its downstream antioxidant-related genes in the mouse liver [17]. …”

“…However, it is crucial to note that there is a paucity of “human studies” to investigate the effects of astaxanthin treatment on liver function in the clinical setting. Two animal studies have investigated the level of ALT, a clinically well-used marker specific to liver function, was examined under astaxanthin treatment [16, 17]; one study showed that astaxanthin significantly reduced blood ALT levels in mice [17], but in another study, astaxanthin did not change the ALT levels in rats following ischemia-reperfusion injury [16]. Before astaxanthin is confirmed as protective to liver, accumulation of data from such human studies is needed.…”