Trans-resveratrol induces a potential anti-lipogenic effect in lipopolysaccharide-stimulated enterocytes

Background: Resveratrol has been demonstrated to exert pleiotropic health beneficial effects. Among the various mechanisms of action antioxidant, anti-inflammatory, cardio- and cancer-protective outcomes have been reported. Particularly, an important function of this natural compound against atherosclerosis has been postulated and the action of resveratrol on lipids and lipoprotein levels seems to be of relevance in this pathology, but also for other metabolic diseases. Accordingly, taking into consideration the straight contact of resveratrol with the intestine, this study aimed to gain insights into the protective effects of trans-resveratrol on enterocyte physiology and metabolism in proinflammatory conditions. For this purpose, a DNA microarray analysis was conducted in Caco-2 cells where global gene expression profile at intestinal level was screened. Cells were pretreated with 50 of trans-resveratrol and, subsequently, lipopolysaccharide (LPS) was added for 48 h. Results: The microarray analysis revealed 121 genes differentially expressed between resveratrol-treated and non-treated cells (B> 0). Four genes, inhibitor of DNA binding 1(ID1), histidine-rich glycoprotein (HRG), NADPH oxidase (NOX1) and sprouty homolog 1 (SPRY), were upregulated by LPS treatment, but significantly downregulated with trans-resveratrol pretreatment (padj< 0.05). Moreover, genes implicated in pathways related to lipid metabolism, such as synthesis of lipids (z-score= -1.195) and concentration of cholesterol (z-score= -0.109), were markedly downregulated by trans-resveratrol. Other genes implicated in lipid metabolism, but also in cell death and survival function, such as transcription factors Krppel-like factor 5 (KLF5) and amphiregulin (AREG), were also significantly inhibited by trans-resveratrol pretreatment. RT-qPCR-data confirmed the microarray results. Special mention deserves acyl-CoA synthetase long-chain family member 3 (ACSL3) and endothelial lipase (LIPG), which were downregulated by the stilbene and have been previously associated with fatty acid synthesis and obesity in other tissues. Conclusions: This study envisages that trans-resveratrol might exert important anti-lipogenic effect at intestinal level under proinflammatory conditions, which have not been previously described.

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