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Docosahexaenoic acid attenuates hepatic inflammation, oxidative stress, and fibrosis without decreasing hepatosteatosis in a Ldlr(-/-) mouse model of western diet-induced nonalcoholic steatohepatitis.
J Nutr. 2013 Mar; 143(3):315-23.JN

Abstract

The incidence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has increased in parallel with the incidence of obesity. While both NAFLD and NASH are characterized by hepatosteatosis, NASH is characterized by hepatic damage, inflammation, oxidative stress, and fibrosis. We previously reported that feeding Ldlr(-/-) mice a high-fat, high-cholesterol diet containing menhaden oil attenuated several markers of NASH, including hepatosteatosis, inflammation, and fibrosis. Herein, we test the hypothesis that DHA [22:6 (n-3)] is more effective than EPA [20:5 (n-3)] at preventing Western diet (WD)-induced NASH in Ldlr(-/-) mice. Mice were fed the WD supplemented with either olive oil (OO), EPA, DHA, or EPA + DHA for 16 wk. WD + OO feeding induced a severe NASH phenotype, characterized by robust hepatosteatosis, inflammation, oxidative stress, and fibrosis. Whereas none of the C20-22 (n-3) fatty acid treatments prevented WD-induced hepatosteatosis, all 3 (n-3) PUFA-containing diets significantly attenuated WD-induced inflammation, fibrosis, and hepatic damage. The capacity of dietary DHA to suppress hepatic markers of inflammation (Clec4F, F4/80, Trl4, Trl9, CD14, Myd88), fibrosis (Procol1α1, Tgfβ1), and oxidative stress (NADPH oxidase subunits Nox2, p22phox, p40phox, p47phox, p67phox) was significantly greater than dietary EPA. The effects of DHA on these markers paralleled DHA-mediated suppression of hepatic Fads1 mRNA abundance and hepatic arachidonic acid content. Because DHA suppression of NASH markers does not require a reduction in hepatosteatosis, dietary DHA may be useful in combating NASH in obese humans.

Authors+Show Affiliations

The Nutrition Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

23303872

Citation

Depner, Christopher M., et al. "Docosahexaenoic Acid Attenuates Hepatic Inflammation, Oxidative Stress, and Fibrosis Without Decreasing Hepatosteatosis in a Ldlr(-/-) Mouse Model of Western Diet-induced Nonalcoholic Steatohepatitis." The Journal of Nutrition, vol. 143, no. 3, 2013, pp. 315-23.
Depner CM, Philbrick KA, Jump DB. Docosahexaenoic acid attenuates hepatic inflammation, oxidative stress, and fibrosis without decreasing hepatosteatosis in a Ldlr(-/-) mouse model of western diet-induced nonalcoholic steatohepatitis. J Nutr. 2013;143(3):315-23.
Depner, C. M., Philbrick, K. A., & Jump, D. B. (2013). Docosahexaenoic acid attenuates hepatic inflammation, oxidative stress, and fibrosis without decreasing hepatosteatosis in a Ldlr(-/-) mouse model of western diet-induced nonalcoholic steatohepatitis. The Journal of Nutrition, 143(3), 315-23. https://doi.org/10.3945/jn.112.171322
Depner CM, Philbrick KA, Jump DB. Docosahexaenoic Acid Attenuates Hepatic Inflammation, Oxidative Stress, and Fibrosis Without Decreasing Hepatosteatosis in a Ldlr(-/-) Mouse Model of Western Diet-induced Nonalcoholic Steatohepatitis. J Nutr. 2013;143(3):315-23. PubMed PMID: 23303872.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Docosahexaenoic acid attenuates hepatic inflammation, oxidative stress, and fibrosis without decreasing hepatosteatosis in a Ldlr(-/-) mouse model of western diet-induced nonalcoholic steatohepatitis. AU - Depner,Christopher M, AU - Philbrick,Kenneth A, AU - Jump,Donald B, Y1 - 2013/01/09/ PY - 2013/1/11/entrez PY - 2013/1/11/pubmed PY - 2013/4/10/medline SP - 315 EP - 23 JF - The Journal of nutrition JO - J. Nutr. VL - 143 IS - 3 N2 - The incidence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has increased in parallel with the incidence of obesity. While both NAFLD and NASH are characterized by hepatosteatosis, NASH is characterized by hepatic damage, inflammation, oxidative stress, and fibrosis. We previously reported that feeding Ldlr(-/-) mice a high-fat, high-cholesterol diet containing menhaden oil attenuated several markers of NASH, including hepatosteatosis, inflammation, and fibrosis. Herein, we test the hypothesis that DHA [22:6 (n-3)] is more effective than EPA [20:5 (n-3)] at preventing Western diet (WD)-induced NASH in Ldlr(-/-) mice. Mice were fed the WD supplemented with either olive oil (OO), EPA, DHA, or EPA + DHA for 16 wk. WD + OO feeding induced a severe NASH phenotype, characterized by robust hepatosteatosis, inflammation, oxidative stress, and fibrosis. Whereas none of the C20-22 (n-3) fatty acid treatments prevented WD-induced hepatosteatosis, all 3 (n-3) PUFA-containing diets significantly attenuated WD-induced inflammation, fibrosis, and hepatic damage. The capacity of dietary DHA to suppress hepatic markers of inflammation (Clec4F, F4/80, Trl4, Trl9, CD14, Myd88), fibrosis (Procol1α1, Tgfβ1), and oxidative stress (NADPH oxidase subunits Nox2, p22phox, p40phox, p47phox, p67phox) was significantly greater than dietary EPA. The effects of DHA on these markers paralleled DHA-mediated suppression of hepatic Fads1 mRNA abundance and hepatic arachidonic acid content. Because DHA suppression of NASH markers does not require a reduction in hepatosteatosis, dietary DHA may be useful in combating NASH in obese humans. SN - 1541-6100 UR - https://www.unboundmedicine.com/medline/citation/23303872/Docosahexaenoic_acid_attenuates_hepatic_inflammation_oxidative_stress_and_fibrosis_without_decreasing_hepatosteatosis_in_a_Ldlr__/___mouse_model_of_western_diet_induced_nonalcoholic_steatohepatitis_ L2 - https://academic.oup.com/jn/article-lookup/doi/10.3945/jn.112.171322 DB - PRIME DP - Unbound Medicine ER -