Suppression of high-fat diet-induced obesity-associated liver mitochondrial dysfunction by docosahexaenoic acid and hydroxytyrosol co-administration

被引:109
作者
Ortiz, Macarena [1 ]
Soto-Alarcon, Sandra A. [2 ]
Orellana, Paula [2 ]
Espinosa, Alejandra [3 ]
Campos, Cristian [3 ]
Lopez-Arana, Sandra [2 ]
Rincon, Miguel A. [4 ]
Illesca, Paola [5 ]
Valenzuela, Rodrigo [2 ]
Videla, Luis A. [6 ]
机构
[1] Catholic Univ Maule, Fac Hlth Sci, Nutr & Dietet Sch, Curico, Chile
[2] Univ Chile, Fac Med, Nutr Dept, Independencia 1027, Santiago 70000, Chile
[3] Univ Chile, Fac Med, Dept Med Technol, Santiago, Chile
[4] Univ Chile, Inst Nutr & Food Technol, Santiago, Chile
[5] Univ Litoral, Fac Biochem, Biochem Dept, Santa Fe, Argentina
[6] Univ Chile, Fac Med, Inst Biomed Sci, Mol & Clin Pharmacol Program, Santiago, Chile
关键词
High-fat diet; Liver steatosis; Mitochondrial dysfunction; Docosahexaenoic acid; Hydroxytyrosol; NF-KAPPA-B; INDUCED HEPATIC STEATOSIS; PPAR-ALPHA; OXIDATIVE STRESS; NONALCOHOLIC STEATOHEPATITIS; DNA-BINDING; N-3; LCPUFA; RECEPTOR; DISEASE; OIL;
D O I
10.1016/j.dld.2020.04.019
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Objective: Obesity-induced by high-fat diet (HFD) is associated with liver steatosis, oxidative stress and mitochondrial dysfunction, which can be eluded by the co-administration of the lipid metabolism modulator docosahexaenoic acid (DHA) and the antioxidant hydroxytyrosol (HT). Methods: C57BL/6J mice fed a HFD were orally administered either with vehicle, DHA, HT or DHA+ HT for 12 weeks. We measured parameters related to insulin resistance, serum lipid levels, liver fatty acid (FA) content and steatosis score, concomitantly with those associated with mitochondrial energy functions modulated by the transcriptional coactivator PGC-1a. Results: HFD induced insulin resistance, liver steatosis with n-3 FA depletion, and loss of mitochondrial respiratory functions with diminished NAD(+) /NADH ratio and ATP levels compared with CD, with the parallel decrease in the expression of the components of the PGC-1 alpha cascade, namely, PPAR-alpha, FGF21 and AMPK, effects that were not observed in mice subjected to DHA and HT co-administration. Conclusions: Data presented indicate that the combination of DHA and HT prevents the development of liver steatosis and the associated mitochondrial dysfunction induced by HFD, thus strengthening the significance of this protocol as a therapeutic strategy avoiding disease evolution into more irreversible forms characterised by the absence of adequate pharmacological therapy in human obesity. (c) 2020 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.
引用
收藏
页码:895 / 904
页数:10
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