Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia.
Department of Anatomy, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Biofactors. 2022 Mar;48(2):498-513. doi: 10.1002/biof.1804. Epub 2021 Nov 12.
This study investigated the effects of omega-3 oils (OM) and/or vitamin D (VD) against metabolic dysfunction-associated fatty liver disease (MAFLD). Forty rats were divided into negative (NC) and positive (PC) controls, OM, VD, and OM + VD groups, and MAFLD was induced by high-fat/high-fructose diet (12 weeks). Oral OM (415 mg/kg/day) and/or intramuscular VD (290 IU/kg/day) were given for 4 weeks (5 times/week). The PC animals were markedly obese and had hyperglycemia, insulin resistance, dyslipidemia, elevated liver enzymes, abnormal hepatic histology, and increased caspase-3 with apoptosis than the NC group. The expression of hepatic peroxisome proliferator-activated receptor-α (PPAR-α; 5.3-fold), insulin induced gene-1 (INSIG1; 7.8-fold), adiponectin receptor-1 (AdipoR1; 4.4-fold), and leptin receptor (LEPR; 6-fold) declined, while PPAR-γ (3.7-fold) and sterol regulatory element-binding protein-1 (SREBP1; 2.4-fold) increased, in the PC than the NC group. Leptin (2.2-fold), malondialdehyde (2.1-fold), protein carbonyl groups (17.3-fold), IL-1β (4.4-fold), IL-6 (2.1-fold), TNF-α (1.8-fold) also increased, whereas adiponectin (2.8-fold) glutathione (2.1-fold), glutathione peroxidase-1 (2.4-fold), glutathione reductase (2.2-fold), catalase (1.4-fold), and IL-10 (2.8-fold) decreased, in the PC livers. Both monotherapies attenuated obesity, metabolic profiles, and PPAR-γ/SREBP1/leptin/Caspase-3/apoptosis, while induced PPAR-α/adiponectin/AdipoR1/LEPR/INSIG1. The monotherapies also reduced the oxidative stress and pro-inflammatory markers and increased the antioxidant and anti-inflammatory molecules. However, the OM effects were better than VD monotherapy. Alternatively, the co-therapy group showed the greatest ameliorations in liver functions, lipid-regulatory molecules, oxidative stress, inflammation, and apoptosis. In conclusion, while OM monotherapy was superior to VD, the co-therapy protocol displayed the best alleviations against MAFLD, possibly by enhanced modulation of metabolic, antioxidant, and anti-inflammatory pathways.
本研究旨在探讨ω-3 油（OM）和/或维生素 D（VD）对代谢相关脂肪性肝病（MAFLD）的影响。将 40 只大鼠分为阴性（NC）和阳性（PC）对照组、OM 组、VD 组和 OM+VD 组，并通过高脂肪/高果糖饮食（12 周）诱导 MAFLD。OM 组（415mg/kg/天）和/或 VD 组（290IU/kg/天）经口给予 4 周（每周 5 次）。PC 动物明显肥胖，并伴有高血糖、胰岛素抵抗、血脂异常、肝酶升高、肝组织学异常和 caspase-3 增加伴凋亡，与 NC 组相比。肝脏过氧化物酶体增殖物激活受体-α（PPAR-α；5.3 倍）、胰岛素诱导基因 1（INSIG1；7.8 倍）、脂联素受体 1（AdipoR1；4.4 倍）和瘦素受体（LEPR；6 倍）的表达下降，而 PPAR-γ（3.7 倍）和固醇调节元件结合蛋白-1（SREBP1；2.4 倍）在 PC 组中增加，与 NC 组相比。与 NC 组相比，leptin（2.2 倍）、丙二醛（2.1 倍）、蛋白质羰基（17.3 倍）、IL-1β（4.4 倍）、IL-6（2.1 倍）、TNF-α（1.8 倍）也增加，而 adiponectin（2.8 倍）、谷胱甘肽（2.1 倍）、谷胱甘肽过氧化物酶-1（2.4 倍）、谷胱甘肽还原酶（2.2 倍）、过氧化氢酶（1.4 倍）和 IL-10（2.8 倍）在 PC 肝脏中减少。两种单药治疗均能减轻肥胖、代谢谱和 PPAR-γ/SREBP1/leptin/Caspase-3/apoptosis，同时诱导 PPAR-α/脂联素/AdipoR1/LEPR/INSIG1。单药治疗还降低了氧化应激和促炎标志物，并增加了抗氧化和抗炎分子。然而，OM 治疗的效果优于 VD 单药治疗。相反，联合治疗组在改善肝功能、脂质调节分子、氧化应激、炎症和细胞凋亡方面表现出最大的改善。总之，OM 单药治疗优于 VD，联合治疗方案对 MAFLD 的缓解作用最好，可能是通过增强代谢、抗氧化和抗炎途径的调节。
