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Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease

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World Journal of Hepatology 2024年第5期16卷 832-842页

作者： Elisa Carolina Lange pabulo henrique rampelotto Larisse Longo Laura Bainy Rodrigues de Freitas Carolina Uribe-Cruz Mario Reis Alvares-da-Silva Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Brazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-007Brazil Bioinformatics and Biostatistics Core Facility Universidade Federal do Rio Grande do SulPorto Alegre 91501-970Brazil Graduate Program in Biological Sciences:Pharmacology and Therapeutics Universidade Federal do Rio Grande do SulPorto Alegre 90035-007Brazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadasMisiones 3300Argentina Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007RSBrazil Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)researcher Brasília 71605-001Brazil

BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic *** suggest ornithine aspartate(LOLA)as drug *** To analyze the influence of LOLA intake on gut microbiota using a nutritional model of *** Adult male Sprague Dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLD(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were *** fecal DNA extraction,the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™*** Alpha and beta diversity metrics were comparable between MASLD and LOLA.3 OTUs were differentially abundant between MASLD and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides *** functional prediction provided two different metabolic profiles between MASLD and *** 9 pathways differentially abundant in MASLD are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides *** 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA *** Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD,it was associated with changes in specific gut microbes and their related metabolic pathways.

关键词： Animal model Gut microbiota Metabolic-associated steatotic liver disease Metabolic prediction Ornithine aspartate

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Gut dysbiosis and systemic inflammation promote cardiomyocyte abnormalities in an experimental model of steatohepatitis

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World Journal of Hepatology 2021年第12期13卷 2052-2070页

作者： Larisse Longo pabulo henrique rampelotto Eduardo Filippi-Chiela Valessa Emanoele Gabriel de Souza Fernando Salvati Carlos Thadeu Cerski Themis Reverbel da Silveira Cláudia P Oliveira Carolina Uribe-Cruz Mário ReisÁlvares-da-Silva Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Graduate Program in Genetics and Molecular Biology Universidade Federal do Rio Grande do SulPorto Alegre 90035-903Rio Grande do SulBrazil Center of Biotechnology Universidade Federal do Rio Grande do SulPorto Alegre 91501-970Rio Grande do SulBrazil Department of Morphological Sciences Universidade Federal do Rio Grande do SulPorto Alegre 90050-170Rio Grande do SulBrazil Experimental Research Center Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil School of Medicine Instituto Meridional de Educação-IMEDPasso Fundo 99070-220Rio Grande do SulBrazil Unit of Surgical Pathology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Department of Gastroenterology(LIM07) Faculdade de Medicina da Universidade de São PauloSão Paulo 01246903Brazil Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil

BACKGROUND Cardiovascular disease is the main cause of death in metabolic-associated fatty liver disease,and gut microbiota dysbiosis is associated with both of *** To assess the relationship between gut dysbiosis and cardiovascular risk(CVR)in an experimental model of *** Adult male Sprague-Dawley rats were randomized to a control group(n=10)fed a standard diet and an intervention group(n=10)fed a high-fat choline-deficient diet for 16 ***,molecular,hepatic,and cardiac *** microbiota variables were *** The intervention group had a significantly higher atherogenic coefficient,Castelli’s risk index(CRI)-I and CRI-II,interleukin-1β,tissue inhibitor of metalloproteinase-1(all P<0.001),monocyte chemoattractant protein-1(P=0.005),and plasminogen activator inhibitor-1(P=0.037)than the control *** expression of miR-33a increased(P=0.001)and miR-126(P<0.001)decreased in the intervention *** with fibrosis was seen in the intervention group,and heart computerized histological imaging analysis showed a significant decrease in the percentage of cardiomyocytes with a normal morphometric appearance(P=0.007),reduction in the mean area of cardiomyocytes(P=0.037),and an increase of atrophic cardiomyocytes(P=0.007).There were significant correlations between the cardiomyocyte morphometry markers and those of progression and severity of liver disease and *** intervention group had a lower Shannon diversity index and fewer changes in the structural pattern of gut microbiota(both P<0.001)than *** microbial families that are involved in lipid metabolism were differentially abundant in intervention group and were significantly correlated with markers of liver injury and *** The study found a link between gut dysbiosis and significant cardiomyocyte abnormalities in animals with steatohepatitis.

关键词： Animal model Cardiovascular diseases Gut microbiota Metabolic-associated fatty liver disease Predicted lipid metabolism Risk cardiovascular Steatohepatitis

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