Metabolic-associated fatty liver disease (MAFLD) is characterized by hepatic steatosis accompanied by one of three features: overweight or obesity, T2DM, or lean or normal weight with evidence of metabolic dysregulation. It is distinguished by excessive fat accumulation in hepatocytes, and a decrease in the liver's ability to oxidize fats, the accumulation of ectopic fat, and the activation of proinflammatory pathways. Chronic damage will keep this pathophysiologic cycle active causing progression from hepatic steatosis to cirrhosis and eventually, hepatocarcinoma. Epigenetics affecting gene expression without altering DNA sequence allows us to study MAFLD pathophysiology from a different perspective, in which DNA methylation processes, histone modifications, and miRNAs expression have been closely associated with MAFLD progression. However, these considerations also faced us with the circumstance that modifying those epigenetics patterns might lead to MAFLD regression. Currently, epigenetics is an area of great interest because it could provide new insights in therapeutic targets and non-invasive biomarkers. This review comprises an update on the role of epigenetic patterns, as well as innovative therapeutic targets and biomarkers in MAFLD.
AbstractmiRNAs are involved in the development of metabolic associated fatty liver disease (MAFLD) and nonalcoholic steatohepatitis (NASH). We aimed to evaluate modifications by prolonged-release pirfenidone (PR-PFD) on key hepatic miRNAs expression in a MAFLD/NASH model. First, male C57BL/6J mice were randomly assigned into groups and fed with conventional diet (CVD) or high fat and carbohydrate diet (HFD) for 16 weeks. At the end of the eighth week, HFD mice were divided in two and only one half was treated with 300 mg/kg/day of PR-PFD mixed with food. Hepatic expression of miRNAs and target genes that participate in inflammation and lipid metabolism was determined by qRT-PCR and transcriptome by microarrays. Increased hepatic expression of miR-21a-5p, miR-34a-5p, miR-122-5p and miR-103-3p in MAFLD/NASH animals was reduced with PR-PFD. Transcriptome analysis showed that 52 genes involved in lipid and collagen biosynthesis and inflammatory response were downregulated in PR-PFD group. The expression of Il1b, Tnfa, Il6, Tgfb1, Col1a1, and Srebf1 were decreased in PR-PFD treated animals. MAFLD/NASH animals compared to CVD group showed modifications in gene metabolic pathways implicated in lipid metabolic process, inflammatory response and insulin resistance; PR-PFD reversed these modifications.
Background and aims. Metabolic Associated Fatty Liver Disease (MAFLD) encompasses a spectrum of diseases from simple steatosis to nonalcoholic steatohepatitis (NASH). Here, we investigated the hepatoprotective role of Moringa oleifera aqueous extract on hepatic miRNAs, genes and protein expression, as well as histological and biochemical parameters in an experimental model of NASH. Methods. Male C57BL/6J mice were fed with a high fat diet (HFD, 60% lipids, 42 gr/L sugar in water) for 16 weeks. Moringa extract was administered via gavage during the final 8 weeks. Insulin Tolerance Test (ITT) and HOMA-IR were calculated. Serum levels of insulin, resistin, leptin and PAI-1 and hepatic expression of miR-21a-5p, miR-103-3p, miR-122-5p, miR-34a-5p and SIRT1, AMPKα and SREBP1c protein were evaluated. Alpha-SMA immunohistochemistry and hematoxylin-eosin, Masson’s trichrome and sirius red staining were made. Hepatic transcriptome was analyzed using microarrays. Results. Animals treated with Moringa extract improved ITT and decreased SREBP1c hepatic protein, while SIRT1 increased. Hepatic expression of miR-21a-5p, miR-103-3p and miR-122-5p, miR34a-5p was downregulated. Hepatic histologic analysis showed in Moringa group (HF + MO) a significant decrease in inflammatory nodules, macro steatosis, fibrosis, collagen and αSMA reactivity. Analysis of hepatic transcriptome showed down expression of mRNAs implicated in DNA response to damage, endoplasmic reticulum stress, lipid biosynthesis and insulin resistance. Moringa reduced insulin resistance, de novo lipogenesis, hepatic inflammation and ER stress. Conclusions. Moringa prevented progression of liver damage in a model of NASH and improved biochemical, histological and hepatic expression of genes and miRNAs implicated in MAFLD/NASH development.
Diet containing Mexican ancestral foods such as cocoa, nopal, avocado, and common bean have been individually reported to have beneficial effects on obesity and comorbidities. Methods: A systematic review and meta-analysis on the effect of Mexican ancestral foods on the anthropometric, lipid, and glycemic control variables in obese patients was performed following PRISMA guidelines. Data were analyzed using a random-effects model. Results: We selected 4664 articles from an initial search, of which only fifteen studies satisfied the inclusion criteria. Data for 1670 participants were analyzed: 843 in the intervention group and 827 in the control group. A significant reduction in body mass index (mean difference: −0.80 (−1.31 to −0.30)) (95% confidence interval), p = 0.002, heterogeneity I2 = 92% was showed after the ingestion of cocoa, nopal, avocado, or common bean. The mean difference for body weight was −0.57 (−1.93 to 0.79), waist of circumference: −0.16 (−2.54 to −2.21), total cholesterol: −5.04 (−11.5 to 1.08), triglycerides: −10.11 (−27.87 to 7.64), fasting glucose: −0.81 (−5.81 to 4.19), and insulin: −0.15 (−0.80 to 0.50). Mexican ancestral food supplementation seems to improve anthropometric, lipid, and glycemic control variables in obesity; however, more randomized controlled trials are needed to have further decisive evidence about dosage and method of supplementation and to increase the sample size.
Research Article OJGH (2019) 2:27 Gallic acid produces hepatoprotection by modulating EGFR expression and phosphorylation in induced preneoplastic liver foci in rats The purpose of this study was to analyze the role of gallic acid as liver protector and identify its role in the regulation of EGFR expression and phosphorylation in induced preneoplastic liver lesions in rats. Male Wistar rats were randomly divided into four groups. (1) Control; (2) animals receiving gallic acid (AG) 50 mg/ kg v.o. for 8 weeks; (3) animals with preneoplasia (P) induced by a single dose of diethylnitrosamine 200 mg/kg i.p. (DEN) and two weeks after a single dose of carbon tetrachloride 2 mL/kg i.p. (CCl4); and (4) animals with preneoplasia treated with GA during 8 weeks. In order to evaluate GA hepatoprotection on preneoplastic lesions, we performed histological examination of liver tissue using H&E staining as well as an immunohistochemical analysis for PCNA. To evaluate the effect of GA on EGFR expression and phosphorylation, we performed an immunohistochemical and western blot analysis. The results indicated that GA significantly decreased EGFR expression and pY1068 EGFR phosphorylation in animals with preneoplastic lesions. GA significantly decreased PCNA expression in animals with preneoplastic lesions, suggesting it may work as an antiproliferative agent. Additionally, GA improved the architecture and organization of liver tissue and significantly decreased serum AST, ALT and FA, which are indicators of hepatocellular damage. By histopathological and immunohistochemical analysis we demonstrated an improvement in liver morphology, a reduction of preneoplastic liver foci and a reduction of cell proliferation, as well as an improvement on liver functionality. In conclusion, GA produces hepatoprotection by modulating EGFR expression and phosphorylation in preneoplastic lesions.
En el presente estudio se elaboró un producto de limpieza de origen natural utilizando el extracto de hojas de Cymbogon Citratus estas presentan propiedades repelentes y relajantes como una alternativa interesante como coadyuvante en la prevención de la picadura del mosquito Aedes Aegypti transmisor del dengue. El Cymbogon Citratus contiene compuestos químicos como saponinas, taninos, antraquinonas, flavonoides, fenoles y alcaloides, además de terpenos, aldehídos, alcoholes y ésteres los cuales cuentan con propiedades prometedoras para diseñar productos que se aplican sobre las diversas zonas de la piel expuesta con el fin de protegerla creando una barrera contra las picaduras de distintos tipos de insectos. Con base en lo anterior, el dengue es una enfermedad viral transmitida por la picadura del mosquito Aedes Aegipty. En Jalisco se ha identificado un incremento en los casos reportados en los últimos años, lo que podría deberse a factores como el cambio climático, alteraciones en su habitad natural o la falta de medidas sanitarias adecuadas, el dengue ha sido uno de los principales problemas a enfrentar para el sector de salud pública a nivel nacional. La elaboración de un producto de limpieza con propiedades relajantes y repelentes, sumado a su fácil aplicación, permitirá que esta problemática que aqueja a distintos sectores de la población disminuya, aportando novedosas alternativas en el desarrollo de diversos coadyuvantes ecológicos.
La obesidad es una patología multifactorial caracterizada por un exceso de grasa corporal y representa un alarmante problema de salud debido a su alta prevalencia. Desafortunadamente, los cambios notorios en la industrialización de los alimentos y el estilo de vida actual han incrementado el consumo de alimentos ricos en grasas y azúcares, dejando a un lado la ingesta de alimentos saludables. Los alimentos ancestrales empleados en México como el cacao, el frijol común, el nopal, el grillo y el aguacate contienen componentes con actividad antioxidante, antiinflamatoria, hipoglucemiante y favorecen la disminución de niveles de colesterol y lípidos.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.