6533b853fe1ef96bd12ad524

RESEARCH PRODUCT

Coffee Restores Expression of lncRNAs Involved in Steatosis and Fibrosis in a Mouse Model of NAFLD

Salvatore PiroStefania Di MauroAlessandra ScamporrinoMaria GuidoRosaria Maria PipitoneAgnese FilippelloValentina CossigaRoberta MalaguarneraFrancesco PurrelloFederico SalomoneVincenzo LemboFilomena MoriscoStefania Grimaudo

subject

lncRNA.Liver CirrhosisMalemedicine.medical_specialtyGm16551; H19; NAFLD; coffee; lncRNA; Animals; Coffee; Disease Models Animal; Fatty Liver; Gene Expression; Liver; Liver Cirrhosis; Male; Mice; Mice Inbred C57BL; Non-alcoholic Fatty Liver Disease; RNA Long NoncodingCoenzyme ACircadian clockcoffeeGene ExpressionBiologyInbred C57BLArticlechemistry.chemical_compoundMicelncRNADownregulation and upregulationFibrosisSettore BIO/13 - Biologia ApplicataNon-alcoholic Fatty Liver DiseaseInternal medicineNAFLDmedicineAnimalsTX341-641Messenger RNANutrition and DieteticsH19Nutrition. Foods and food supplyAnimalGm16551Fatty liverNAFLD; coffee; lncRNA; Gm16551; H19nutritional and metabolic diseasesmedicine.diseaseMice Inbred C57BLFatty LiverDisease Models AnimalEndocrinologychemistryLiverLipogenesisDisease ModelsRNARNA Long NoncodingLong NoncodingSteatosisFood Science

description

Background and aim: Coffee intake exerts protective effects against non-alcoholic fatty liver disease (NAFLD), although without fully cleared mechanisms. In this study we aimed to assess whether coffee consumption may influence the expression of long non-coding RNAs (lncRNAs) in the liver. Methods: C57BL/6J mice were fed a 12-week standard diet (SD), high-fat diet (HFD) or HFD plus decaffeinated coffee solution (HFD + coffee). Expression of specific lncRNAs involved in NAFLD was analyzed by real-time PCR. For the most differentially expressed lncRNAs, the analysis was also extended to their mRNA targets. Results: Decaffeinated coffee intake reduced body weight gain, prevented NAFLD, lowered hyperglycemia and hypercholesterolemia. NAFLD was associated with lower hepatic expression of Gm16551, a lncRNA inhibiting de novo lipogenesis, and higher expression of H19, a lncRNA promoting fibrogenesis. Coffee intake restored Gm16551 to levels observed in lean mice and downregulated gene expression of its targets acetyl coenzyme A carboxylase 1 and stearoyl coenzyme A desaturase 1. Furthermore, coffee consumption markedly decreased hepatic expression of H19 and of its target gene collagen alpha-1(I) chain; consistently, in mice fed HFD + coffee liver expression of αSMA protein returned to levels of mice fed SD. Expression of lncRNA involved in circadian clock such as fatty liver-related lncRNA 1 (FLRL1) and fatty liver-related lncRNA 2 (FLRL2) were upregulated by HFD and were also modulated by coffee intake. Conclusion. Hepatoprotective effects of coffee may be depending on the modulation of lncRNAs involved in key pathways of NAFLD onset and progression.

10.3390/nu13092952http://hdl.handle.net/11577/3451160