A 9-cis β-Carotene–Enriched Diet Inhibits Atherogenesis and Fatty Liver Formation in LDL Receptor Knockout Mice

Abstract

Our aim was to study the effect of 9-cis beta-carotene-rich powder of the alga Dunaliella bardawil on lipid profile, atherogenesis, and liver steatosis in high-fat diet-fed LDL receptor knockout mice. In 4 sets of experiments, mice were distributed into the following groups: control, fed an unfortified diet; Dunaliella 50, fed a diet composed of 50% 9-cis and 50% all-trans beta-carotene; Dunaliella 25, fed a diet containing 25% 9-cis and 75% all-trans beta-carotene; beta-carotene-deficient Dunaliella, fed beta-carotene-deficient Dunaliella powder; and all-trans beta-carotene, fed a synthetic all-trans beta-carotene. All fortified diets contained 0.6% total beta-carotene. Algal 9-cis beta-carotene was absorbed by the mice and accumulated in the liver. Synthetic all-trans beta-carotene was not converted to 9-cis beta-carotene. Dunaliella 50 inhibited high-fat diet-induced plasma cholesterol elevation by 40-63% and reduced cholesterol concentrations in the atherogenic VLDL and LDL. Atherosclerotic lesion area in mice treated with Dunaliella 50 was 60-83% lower compared with mice fed the high-fat diet alone. beta-Carotene-deficient Dunaliella did not influence plasma cholesterol and atherogenesis, suggesting that beta-carotene is essential for a Dunaliella protective effect. Moreover, by administrating Dunaliella powder containing different levels of 9-cis and all-trans beta-carotene isomers, we found that the effect on plasma cholesterol concentration and atherogenesis is 9-cis-dependent. Dunaliella 50 also inhibited fat accumulation and inflammation in the livers of mice fed a high-fat diet, which was accompanied by reduced mRNA levels of inflammatory genes. These results in mice suggest that 9-cis beta-carotene may have the potential to inhibit atherogenesis in humans.

Low Levels of Serum β-Carotene and β-Carotene/Retinol Ratio Are Associated with Histological Severity in Nonalcoholic Fatty Liver Disease Patients

“…β-Carotene supplementation could alleviate hepatic SS in HFD-fed mice [20]. β-Carotene is able to modulate the nuclear factor κB pathway and nuclear factor erythroid 2-related factor 2 pathway to inhibit downstream production of inflammatory cytokines and oxidative stress [21].…”

Effects of cooking on the profile and micellarization of 9-cis-, 13-cis- and all-trans-β-carotene in green vegetables

“…Although low concentrations are found in circulating human serum, cis-BC isomers are present in human tissues where it is thought that they exert their biological function(s) (Deming, Baker, & Erdman, 2002;Stahl & Sies, 1993). Recently, it has been suggested that cis-BC isomers may also have a role in preventing atherogenesis (Harari et al, 2008); however, studies are still ongoing to fully elucidate these findings.…”

Reduction in hypercholesterolemia and risk of cardiovascular diseases by mixtures of plant food extract: a study on plasma lipid profile, oxidative stress and testosterone in rats

“…Epidemiological studies suggest that a diet rich in carotenoids is associated with a reduced risk of heart disease and cancer (Melendez-Martinez et al, 2004). Harari et al (2008) suggested that 9-cis b-carotene have the potential to inhibit atherogenesis in humans via its conversion to 9-cis retinoic atherogenic effect of the extract mixtures may be due to the presence of phenolic compounds, phytosterols, tocopherols and unsaturated fatty acids. The studied mixtures showed complete safety towards liver and kidney functions.…”