Tomato Juice Supplementation Influences the Gene Expression Related to Steatosis in Rats

Abstract

The objective of this work was to identify the effect of tomato juice on the expression of genes and levels of metabolites related to steatosis in rats. Male Sprague Dawley rats (8 weeks-old) were grouped (6 rats/group) in four experimental groups: NA (normal diet and water), NL (normal diet and tomato juice), HA (high-fat diet and water), and HL (high-fat diet and tomato juice). After an intervention period of 5 weeks, rats were sacrificed and biochemical parameters, biomarkers of oxidative stress, liver metabolites, and gene expression were determined. Although the H diet provoked dislipemia related to steatosis, no changes in isoprostanes or liver malondialdehyde (MDA) were observed. Changes in the gene expression of the HA group were produced by the high consumption of fat, whereas the consumption of tomato juice had different effects, depending on the diet. In the NL group, the genes involved in β-oxidation were upregulated, and in groups NL and HL upregulation of CD36 and downregulation of APOB and LPL were observed. In addition, in the HL group the accumulation of lycopene upregulated the genes FXR and HNF4A, which have been suggested as preventive factors in relation to steatosis. Regarding the metabolomics study, intake of tomato juice stimulated the biosynthesis of glutathione and amino acids of the transulfurization pathway, increasing the levels of metabolites related to the antioxidant response.

Consumption of Spinach and Tomato Modifies Lipid Metabolism, Reducing Hepatic Steatosis in Rats

“…This lipid-lowering effect of carotenoids has been described in other previous studies in obese animals with NAFLD [ 38 , 39 ] and is due to different mechanisms. Thus, lycopene has been shown to have a hypocholesterolemic effect, as it is capable of inhibiting the cholesterol synthesis limiting enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) [ 40 , 41 ], although it is also capable of modulating the expression of genes involved in lipid metabolism, mainly due to the modulation of genes involved in the signaling pathways of PPARs [ 10 , 11 , 12 , 14 ]. The lipid-lowering and hypocholesterolemic effects are directly related to the accumulation of lycopene after ingestion, since this was the majority carotenoid in the experimental diets and the only carotenoid found at the plasma level, with concentrations ranging from 13 to 15 ng/mL, as a function of lycopene concentration in the diets.…”

“…Carotenoid analysis in experimental diets, liver and feces was performed according to the method described by Seybold et al [ 29 ] with some modifications, as have been described in previous investigations [ 11 , 12 , 14 ]. The samples were extracted twice in tetrahydrofuran/methanol (1/1, v / v ) with 0.1% of butylhydroxytoluene, and, after elimination of the solvent, the residues were reconstituted with a TBME/MeOH solution (1:1), centrifuged at 14,000 rpm for 10 min at room temperature and filtered.…”

“…Vegetables such as spinach and tomato are a good source of dietary carotenoids, with values that can reach 10.87 and 7.82 mg/100 g of fresh weight, respectively [ 9 ]. Although carotenoids are recognized as antioxidants, the dietetic supplementation of carotenoids has not been used in the treatment of patients with NAFLD, but its beneficial effects have been studied experimentally using animal models [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”

“…Likewise, changes occurred in the expression of genes related to lipid metabolism, mainly through the overexpression of PPAR [ 14 ]. On the other hand, we found that lycopene-rich tomato juice is a therapeutic agent against NAFLD, since it reduces fat accumulation and inflammation in the liver, increasing the activity of mitochondrial and peroxisomal β-oxidation, the metabolite levels related to the antioxidant response, and modulating the expression of genes involved in lipid metabolism [ 10 , 11 , 12 ]. However, most of these findings related to the beneficial effect of carotenoids in NAFLD were investigated in animal models and were observed when dietary carotenoids were administered together with a high-fat diet.…”

The Molecular and Mechanistic Insights Based on Gut–Liver Axis: Nutritional Target for Non-Alcoholic Fatty Liver Disease (NAFLD) Improvement

“…For example, the inflammatory response in RAW264.7 macrophages or isolated primary macrophages from mice induced by LPS were shown to be mitigated by β-carotene, which was associated with the inactivation of nuclear factor-κB (NF-κB) and enhanced antioxidant capacity [159]. Although few reports support the regulation of carotenoids on bile acids, FXR, a palliative factor for hepatic steatosis, has been shown to be up-regulated in the liver of rats exposed to high-fat diet feeding with lycopene [160]. Polyphenols appertain to a highly diverse category of compounds that present naturally in plants [161].…”