title: A 9-cis beta-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.
authors.affiliation: The Bert W. Strassburger Lipid Center, Tel-Hashomer; Haifa, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Harari
authors.forename: Dror
authors.initials: D
authors.lastname: Harats
authors.forename: Daniella
authors.initials: D
authors.lastname: Marko
authors.forename: Hofit
authors.initials: H
authors.lastname: Cohen
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Kamari
authors.forename: Ayelet
authors.initials: A
authors.lastname: Gonen
authors.forename: Yariv
authors.initials: Y
authors.lastname: Gerber
authors.forename: Ami
authors.initials: A
authors.lastname: Ben-Amotz
authors.forename: Aviv
authors.initials: A
authors.lastname: Shaish
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D004032:Diet; D056890:Eukaryota; D005234:Fatty Liver / Q000517:prevention & control*; D006937:Hypercholesterolemia / Q000517:prevention & control; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency*; D012176:Retinoids / Q000378:metabolism; D019207:beta Carotene / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D011973:Receptors, LDL; D012176:Retinoids; D019207:beta Carotene; D002784:Cholesterol