Unitat de Recerca Biomèdica (CRB-URB) Hospital Universitari de Sant Joan Institut d'Investigació Sanitària Pere Virgili (IISPV) Universitat Rovira i Virgili C/ Sant Joan s/n 43201 Reus SPAIN
Abstract: BACKGROUND: MicroRNAs have the potential for clinical application. Probable modulation by plant-derived polyphenols might open preventive measures using simple dietary recommendations. METHODS: We assessed the ability of continuous administration of high-dose polyphenols to modulate hepatic metabolism and microRNA expression in diet-induced fatty liver disease in commercially available hyperlipidemic mice using well-established and accepted procedures that included the development of new antibodies against modified quercetin. RESULTS: Weight gain, liver steatosis, changes in the composition of liver tissue, and insulin resistance were all attenuated by the continuous administration of polyphenols. We also demonstrated that metabolites of polyphenols accumulate in immune cells and at the surface of hepatic lipid droplets indicating not only bioavailability but a direct likely action on liver cells. The addition of polyphenols also resulted in changes in the expression of miR-103, miR-107 and miR-122. CONCLUSIONS: Polyphenols prevent fatty liver disease under these conditions. The differential expression of mRNAs and miRNAs was also associated with changes in lipid and glucose metabolism and with the activation of 5'-adenosine monophosphate-activated protein kinase, effects that are not necessarily connected. miRNAs function via different mechanisms and miRNA-mRNA interactions are difficult to ascertain with current knowledge. Further, cell models usually elicit contradictory results with those obtained in animal models. General significance Our data indicate that plant-derived polyphenols should be tested in humans as preventive rather than therapeutic agents in the regulation of hepatic fatty acid utilization. A multi-faceted mechanism of action is likely and the regulation of liver miRNA expression blaze new trails in further research.
Abstract: We explored whether the Asp42Gly polymorphism (rs12075) in the DARC gene represents a confounding factor in the interpretation of monocyte chemoattractant protein-1 (MCP-1) concentration in circulating blood.
Abstract: The paraoxonase (PON) group of enzymes, composed of PON1, PON2, and PON3, play an important role in decreasing oxidative stress by degrading lipid peroxides. PON1 synthesis is upregulated by PPAR. Several pharmacological compounds (acting as antioxidants and, hence, atheroprotective) stimulate both PPAR activity and PON1 expression. Recent evidence suggests that PON1 and the monocyte chemoattractant protein-1 (MCP-1) are involved in coordinating the inflammatory response in damaged tissues; PPAR may be central in the regulation of these biochemical pathways. This article reviews the state of knowledge on PON1 biochemistry and function, the influence of genetic variation, and the regulation of PON1 expression by pharmaceutical compounds that increase PPAR activity. We also describe recent lines of evidence suggesting links between PON1 and MCP-1 and how their production may be regulated by PPAR.
Abstract: The recently observed association between the APOC3-related rs10892151 polymorphism and serum triglyceride levels has prompted us the possibility to explore whether this genetic variant may play a major role in human immunodeficiency virus (HIV)/antiretroviral therapy-induced dyslipidemia.
Abstract: Liver steatosis is frequent in patients with chronic hepatitis viral infections. Intracellular fatty acid synthase (FASN) seems to play a substantial role in its pathogenesis. FASN can also be found in circulation and is significantly increased in HIV-infected individuals, especially if they are co-infected with hepatitis C virus (HCV).
