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Eicosapentaenoic acid and docosahexaenoic acid, but not α-linolenic acid, decreased low-density lipoprotein cholesterol synergistically with estrogen via regulation of cholesterol synthesis and clearance in ovariectomized rats.
Nutr Res. 2019 06; 66:13-21.NR

Abstract

Our previous study showed that n-3 polyunsaturated fatty acid (PUFA) and estrogen (E) had synergistic hypocholesterolemic effects by inhibiting cholesterol synthesis and enhancing bile acid synthesis. The purpose of the present study was to investigate the hypothesis that α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) decrease low-density lipoprotein cholesterol (LDL-C), synergistically with E, via hepatic cholesterol synthesis and clearance. Rats were fed a diet with either 0% n-3 PUFA or 1% ALA, EPA, or DHA, relative to total energy consumption, for the entire 12-week study. After ovariectomy, rats were injected with either corn oil or E every 4 days for the last 3 weeks of the study. In combination with E, dietary supplementation with EPA or DHA increased the phosphorylated adenosine monophosphate-activated protein kinase/adenosine monophosphate-activated protein kinase ratio and LDL receptor expression, and it decreased the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase, sterol regulatory element-binding protein-2, and proprotein convertase subtilisin/kexin type 9 in the liver. In addition, dietary supplementation with EPA or DHA increased hepatic expression of cholesterol 7α-hydroxylase, sterol 12α-hydroxylase, and sterol 27-hydroxylase. However, E decreased the expression of cholesterol 7α-hydroxylase and sterol 12α-hydroxylase and increased the expression of estrogen receptor α and β in the liver. ALA had no significant effects on cholesterol metabolism. In conclusion, the present study suggests that dietary supplementation with EPA and DHA decreased LDL-C synthesis and increased bile acid synthesis and LDL-C clearance by LDL receptor, synergistically with E.

Authors+Show Affiliations

Department of Food and Nutrition, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, South Korea.Department of Food and Nutrition, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, South Korea.Department of Food and Nutrition Services, Hanyang University Hospital, 222-1 Wangsimni-ro, Seongdong-gu, Seoul 04763, South Korea.Department of Food and Nutrition, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, South Korea. Electronic address: yongsoon@hanyang.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31051318

Citation

Park, Chung, et al. "Eicosapentaenoic Acid and Docosahexaenoic Acid, but Not Α-linolenic Acid, Decreased Low-density Lipoprotein Cholesterol Synergistically With Estrogen Via Regulation of Cholesterol Synthesis and Clearance in Ovariectomized Rats." Nutrition Research (New York, N.Y.), vol. 66, 2019, pp. 13-21.
Park C, Choi JE, Jin Y, et al. Eicosapentaenoic acid and docosahexaenoic acid, but not α-linolenic acid, decreased low-density lipoprotein cholesterol synergistically with estrogen via regulation of cholesterol synthesis and clearance in ovariectomized rats. Nutr Res. 2019;66:13-21.
Park, C., Choi, J. E., Jin, Y., & Park, Y. (2019). Eicosapentaenoic acid and docosahexaenoic acid, but not α-linolenic acid, decreased low-density lipoprotein cholesterol synergistically with estrogen via regulation of cholesterol synthesis and clearance in ovariectomized rats. Nutrition Research (New York, N.Y.), 66, 13-21. https://doi.org/10.1016/j.nutres.2019.03.003
Park C, et al. Eicosapentaenoic Acid and Docosahexaenoic Acid, but Not Α-linolenic Acid, Decreased Low-density Lipoprotein Cholesterol Synergistically With Estrogen Via Regulation of Cholesterol Synthesis and Clearance in Ovariectomized Rats. Nutr Res. 2019;66:13-21. PubMed PMID: 31051318.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Eicosapentaenoic acid and docosahexaenoic acid, but not α-linolenic acid, decreased low-density lipoprotein cholesterol synergistically with estrogen via regulation of cholesterol synthesis and clearance in ovariectomized rats. AU - Park,Chung, AU - Choi,Jeong-Eun, AU - Jin,Youri, AU - Park,Yongsoon, Y1 - 2019/03/07/ PY - 2018/11/26/received PY - 2019/02/22/revised PY - 2019/03/01/accepted PY - 2019/5/6/pubmed PY - 2019/5/6/medline PY - 2019/5/4/entrez KW - Docosahexaenoic acid KW - Eicosapentaenoic acid KW - Estrogen KW - LDL cholesterol KW - Ovariectomized rats KW - Proprotein convertase subtilisin/kexin type 9 SP - 13 EP - 21 JF - Nutrition research (New York, N.Y.) JO - Nutr Res VL - 66 N2 - Our previous study showed that n-3 polyunsaturated fatty acid (PUFA) and estrogen (E) had synergistic hypocholesterolemic effects by inhibiting cholesterol synthesis and enhancing bile acid synthesis. The purpose of the present study was to investigate the hypothesis that α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) decrease low-density lipoprotein cholesterol (LDL-C), synergistically with E, via hepatic cholesterol synthesis and clearance. Rats were fed a diet with either 0% n-3 PUFA or 1% ALA, EPA, or DHA, relative to total energy consumption, for the entire 12-week study. After ovariectomy, rats were injected with either corn oil or E every 4 days for the last 3 weeks of the study. In combination with E, dietary supplementation with EPA or DHA increased the phosphorylated adenosine monophosphate-activated protein kinase/adenosine monophosphate-activated protein kinase ratio and LDL receptor expression, and it decreased the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase, sterol regulatory element-binding protein-2, and proprotein convertase subtilisin/kexin type 9 in the liver. In addition, dietary supplementation with EPA or DHA increased hepatic expression of cholesterol 7α-hydroxylase, sterol 12α-hydroxylase, and sterol 27-hydroxylase. However, E decreased the expression of cholesterol 7α-hydroxylase and sterol 12α-hydroxylase and increased the expression of estrogen receptor α and β in the liver. ALA had no significant effects on cholesterol metabolism. In conclusion, the present study suggests that dietary supplementation with EPA and DHA decreased LDL-C synthesis and increased bile acid synthesis and LDL-C clearance by LDL receptor, synergistically with E. SN - 1879-0739 UR - https://www.unboundmedicine.com/medline/citation/31051318/Eicosapentaenoic_acid_and_docosahexaenoic_acid_but_not_α_linolenic_acid_decreased_low_density_lipoprotein_cholesterol_synergistically_with_estrogen_via_regulation_of_cholesterol_synthesis_and_clearance_in_ovariectomized_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0271-5317(18)31341-1 DB - PRIME DP - Unbound Medicine ER -