Vitamin D3 enhances the effects of omega-3 oils against metabolic dysfunction-associated fatty liver disease in rat

Abstract

This study investigated the effects of omega-3 oils (OM) and/or vitamin D3 (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.