title: Trans-resveratrol induces a potential anti-lipogenic effect in lipopolysaccharide-stimulated enterocytes.
abstract: A DNA microarray analysis was conducted in Caco-2 cells to analyse the protective effects of trans-resveratrol on enterocyte physiology and metabolism in pro-inflammatory conditions. Cells were pre-treated with 50 μΜ of trans-resveratrol and, subsequently, lipopolysaccharide (LPS) was added for 48 h. The microarray analysis revealed 121 genes differentially expressed between resveratrol-treated and non-treated cells (B> 0, is the odd thatthe gene is differentially expressed). 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 blocked by trans-resveratrol pre-treatment (padj< 0.05, after adjusting for Benjamini-Hocheberg procedure). Moreover, genes implicated in synthesis of lipids (z-score= -1.195) and concentration of cholesterol (z-score= -0.109), were markedly downregulated by trans-resveratrol. Other genes involved in fat turnover, but also in cell death and survival function, such as transcription factors Krüppel-like factor 5 (KLF5) and amphiregulin (AREG), were also significantly inhibited by trans-resveratrol pre-treatment. 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 this stilbene and have been previously associated with fatty acid synthesis and obesity in other tissues. This study envisages that trans-resveratrol might exert an important anti-lipogenic effect at intestinal level under pro-inflammatory conditions, which has not been previously described.
authors.affiliation: University of Navarra Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research Pamplona Spain.
authors.forename: U
authors.initials: U
authors.lastname: Etxeberria
authors.affiliation: University of Navarra Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research Pamplona Spain.
authors.forename: R
authors.initials: R
authors.lastname: Castilla-Madrigal
authors.affiliation: University of Navarra Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research Pamplona Spain.
authors.forename: M P
authors.initials: MP
authors.lastname: Lostao
authors.affiliation: University of Navarra Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research Pamplona Spain jalfmtz@unav.es.
authors.forename: J A
authors.initials: JA
authors.lastname: Martínez
authors.affiliation: University of Navarra Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research Pamplona Spain.
authors.forename: F I
authors.initials: FI
authors.lastname: Milagro
mesh_terms: D066258:Amphiregulin; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D018938:Caco-2 Cells; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism*; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D066255:EGF Family of Proteins / Q000235:genetics / Q000378:metabolism; D020895:Enterocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D050155:Lipogenesis / Q000187:drug effects* / Q000235:genetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D046228:Microarray Analysis; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011506:Proteins; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*; D000099053:Histidine-Rich Glycoprotein; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D000924:Anticholesteremic Agents; D066255:EGF Family of Proteins; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D010750:Phosphoproteins; D011506:Proteins; C486055:SPRY1 protein, human; D013267:Stilbenes; D000099053:Histidine-Rich Glycoprotein; D002784:Cholesterol; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human; C410382:LIPG protein, human; D008049:Lipase; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; D000077185:Resveratrol