Vitamin <scp>D<sub>3</sub></scp> enhances the effects of omega‐3 oils against metabolic dysfunction‐associated fatty liver disease in rat

Refaat, Bassem; Abdelghany, Abdelghany H.; Ahmad, Jawwad; Abdalla, Osama; Elshopakey, Gehad E.; Idris, Shakir; El‐Boshy, Mohamed

doi:10.1002/biof.1804

Cited by 17 publications

(8 citation statements)

References 62 publications

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“…In accordance with a study by Refaat et al. ( 95 ), the present study demonstrated that VD increased the protein expression of PPARα in the liver. Accordingly, the protein expression of CPT1A was also increased after VD treatment.…”

Section: Discussionsupporting

confidence: 94%

Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

Lian

Zhang

et al. 2023

Front. Endocrinol.

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IntroductionThe study aimed to explore the association of serum 25(OH)D3 and hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) patients and to determine whether the effect of vitamin D (VD) is mediated by activation of the peroxisome proliferator-activated receptor α (PPARα) pathway.MethodsThe study contained a case-control study, in vivo and in vitro experiments. A case-control study was conducted to compare serum parameters between NAFLD patients and controls and to evaluate the association of 25(OH)D3 and NAFLD. In vivo study, male Wistar rats were randomly divided into control and model groups, fed a standard chow diet and a high-fat diet (HFD), respectively, for 7 weeks to generate an NAFLD model. Then, the rats were treated with VD and a PPARα antagonist (MK886) for 7 weeks. Tissue and serum were collected and assessed by biochemical assays, morphological analysis, histological analysis, and western blot analysis. In vitro, HepG2 cells were incubated with oleic acid (OA) to induce steatosis, which was evaluated by staining. HepG2 cells were pretreated with MK886 followed by calcitriol treatment, and differences in lipid metabolism-related proteins were detected by western blot.ResultsNAFLD patients were characterized by impaired liver function, dyslipidemia, and insulin resistance. Serum 25(OH)D3 was negatively associated with alanine aminotransferase (ALT) in NAFLD. VD deficiency was a risk factor for patients with no advanced fibrosis. Adequate VD status (25(OH)D3 >20 ng/mL) had a protective effect in patients after adjustment for confounding variables. NAFLD rats showed hyperlipidemia with severe hepatic steatosis, systematic inflammation, and lower serum 25(OH)D3. VD treatment ameliorated hepatic steatosis both in NAFLD rats and OA-induced HepG2 cells. Further, MK886 inhibited the anti-steatosis effect of VD.ConclusionThe study revealed that an adequate VD level may act as a protective factor in NAFLD and that VD may alleviate hepatic steatosis via the PPARα signaling pathway.

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Section: Discussionsupporting

confidence: 94%

Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

Lian

Zhang

et al. 2023

Front. Endocrinol.

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“…Cell apoptosis was detected in colonic tissues with a Click-iT™ Plus TUNEL Assay (#C10617; Thermo Fisher Scientific) and by following the manufacturer’s instructions. The co-detection of apoptotic bodies with cleaved Casp-3 was achieved by a sequential staining protocol, as described earlier ( 41 , 42 ). Briefly, anti-cleaved Casp-3 rabbit IgG monoclonal antibodies (#9661; Cell Signaling Technology Inc.) were added (1:400 concentration) for 3h following completion of the TUNEL protocol.…”

Section: Methodsmentioning

confidence: 99%

Enhanced anti-cancer effects of oestrogen and progesterone co-therapy against colorectal cancer in males

et al. 2022

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Although ovarian sex steroids could have protective roles against colorectal cancer (CRC) in women, little is currently known about their potential anti-tumorigenic effects in men. Hence, this study measured the therapeutic effects of 17β-oestradiol (E2) and/or progesterone (P4) against azoxymethane-induced CRC in male mice that were divided into (n = 10 mice/group): negative (NC) and positive (PC) controls, E2 (580 µg/Kg/day; five times/week) and P4 (2.9 mg/Kg/day; five times/week) monotherapies, and concurrent (EP) and sequential (E/P) co-therapy groups. Both hormones were injected intraperitoneally to the designated groups for four consecutive weeks. Similar treatment protocols with E2 (10 nM) and/or P4 (20 nM) were also used in the SW480 and SW620 human male CRC cell lines. The PC group showed abundant colonic tumours alongside increased colonic tissue testosterone levels and androgen (AR) and oestrogen (ERα) receptors, whereas E2 and P4 levels with ERβ and progesterone receptor (PGR) decreased significantly compared with the NC group. E2 and P4 monotherapies equally increased ERβ/PGR with p21/Cytochrome-C/Caspase-3, reduced testosterone levels, inhibited ERα/AR and CCND1/survivin and promoted apoptosis relative to the PC group. Both co-therapy protocols also revealed better anti-cancer effects with enhanced modulation of colonic sex steroid hormones and their receptors, with E/P the most prominent protocol. In vitro, E/P regimen showed the highest increases in the numbers of SW480 (2.1-fold) and SW620 (3.5-fold) cells in Sub-G1 phase of cell cycle. The E/P co-therapy also disclosed the lowest percentages of viable SW480 cells (2.8-fold), whilst both co-therapy protocols equally showed the greatest SW620 apoptotic cell numbers (5.2-fold) relative to untreated cells. Moreover, both co-therapy regimens revealed maximal inhibitions of cell cycle inducers, cell survival markers, and AR/ERα alongside the highest expression of cell cycle suppressors, pro-apoptotic molecules, and ERβ/PGR in both cell lines. In conclusion, CRC was associated with abnormal levels of colonic sex steroid hormones alongside aberrant protein expression of their receptors. While the anti-cancer effects of E2 and P4 monotherapies were equal, their combination protocols showed boosted tumoricidal actions against CRC in males, possibly by promoting ERβ and PGR-mediated androgen deprivation together with inhibition of ERα-regulated oncogenic pathways.

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“…There was a reduction in the expression of SREBP-1c and its target genes, fatty acid synthase and acetyl CoA carboxylase, which demonstrated that vitamin D increased the production of antioxidant and anti-inflammatory chemicals. Simultaneously, it triggered the upregulation of hepatic mRNA expression of PPARα and CPT-1 and reduced leptin, induced adiponectin/AdipoR1 with suppression of the p53–p21 pathway of caspase-3/apoptosis, and increased SMP-30 levels [ 68 , 69 , 70 , 71 , 72 ].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D and Swimming Exercise Prevent Obesity in Rats under a High-Fat Diet via Targeting FATP4 and TLR4 in the Liver and Adipose Tissue

Kolieb

Maher

Shalaby

et al. 2022

IJERPH

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The prevalence of obesity has risen in the last decades, and it has caused massive health burdens on people’s health, especially metabolic and cardiovascular issues. The risk of vitamin D insufficiency is increased by obesity, because adipose tissue alters both the requirements for and bioavailability of vitamin D. Exercise training is acknowledged as having a significant and long-term influence on body weight control; the favorable impact of exercise on obesity and obesity-related co-morbidities has been demonstrated via various mechanisms. The current work illustrated the effects of vitamin D supplementation and exercise on obesity induced by a high-fat diet (HFD) and hepatic steatosis in rats and explored how fatty acid transport protein-4 (FATP4) and Toll-like receptor-4 antibodies (TLR4) might be contributing factors to obesity and related hepatic steatosis. Thirty male albino rats were divided into five groups: group 1 was fed a normal-fat diet, group 2 was fed an HFD, group 3 was fed an HFD and given vitamin D supplementation, group 4 was fed an HFD and kept on exercise, and group 5 was fed an HFD, given vitamin D, and kept on exercise. The serum lipid profile adipokines, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were analyzed, and the pathological changes in adipose and liver tissues were examined. In addition, the messenger–ribonucleic acid (mRNA) expression of FATP4 and immunohistochemical expression of TLR4 in adipose and liver tissues were evaluated. Vitamin D supplementation and exercise improved HFD-induced weight gain and attenuated hepatic steatosis, along with improving the serum lipid profile, degree of inflammation, and serum adipokine levels. The expression of FATP4 and TLR4 in both adipose tissue and the liver was downregulated; it was noteworthy that the group that received vitamin D and was kept on exercise showed also improvement in the histopathological picture of this group. According to the findings of this research, the protective effect of vitamin D and exercise against obesity and HFD-induced hepatic steatosis is associated with the downregulation of FATP4 and TLR4, as well as a reduction in inflammation.

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

Cited by 17 publications

References 62 publications

Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

Enhanced anti-cancer effects of oestrogen and progesterone co-therapy against colorectal cancer in males

Vitamin D and Swimming Exercise Prevent Obesity in Rats under a High-Fat Diet via Targeting FATP4 and TLR4 in the Liver and Adipose Tissue

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

Cited by 17 publications

References 62 publications

Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

Enhanced anti-cancer effects of oestrogen and progesterone co-therapy against colorectal cancer in males

Vitamin D and Swimming Exercise Prevent Obesity in Rats under a High-Fat Diet via Targeting FATP4 and TLR4 in the Liver and Adipose Tissue

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