RNA modification may protect against liver disease, explain liver fat differences between sexes

FINDINGSA chemical modification that occurs in some RNA molecules as they carry genetic instructions from DNA to cells ’ protein-making machinery may offer protection against non-alcoholic fatty liver, a condition that results from a build-up of fat in the liver and can lead to advanced liver disease, according to a new study by UCLA researchers.The study, conducted in mice, also suggests that this modification — known as m6A, in which a methyl group attaches to an RNA chain — may occurat a different ratein femalesthan it does inmales, potentially explaining why females tend to have higher fat content in the liver. The researchers found that without the m6A modification, differences in liver fat content between the sexes were reduced dramatically.In addition, in a preclinical model, the investigators demonstrated that gene therapy can be used to enhance or add modifications to key RNAs to slow down or reduce the severity of liver disease.BACKGROUNDFatty liver can develop when liver fat content increases due to dietary or genetic factors, potentially leading to advanced liver scarring and disease, as seen in cirrhosis and other conditions. High liver fat content is also associated with increased risk of cardiovascular disease.In recent years, scientists have identified hundreds of chemical modifications like m6A that can occur in RNA molecules, altering the RNA ’s instructions for making proteins without affecting the core DNA. Some modifications can be...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news

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Contributors : Xuezhu Li ; Dipankar Bhattacharya ; Scott L Friedman ; John C HeSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusNon-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) that underlies a growing prevalence of cirrhosis and liver cancer worldwide. Clinical studies suggest that NASH is an independent risk factor for chronic kidney disease (CKD), but models and mechanisms linking these two diseases are lacking. Here, we have characterized the renal function, histological features, and transcriptomic profile in a well-validated murin...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
In light of a global rise in obesity and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) represent an increasingly important underlying etiology of hepatocellular carcinoma (HCC). HCCs arising from lipotoxicity-mediated chronic inflammation due to excessive accumulation of neutral lipids in the liver are characterized by several unique features: In contrast to viral-driven HCC, up to 50% of NAFLD-HCC occurs in patients without cirrhosis, and annual HCC incidence is comparatively low, complicating current surveillance strategies.
Source: Journal of Hepatology - Category: Gastroenterology Authors: Tags: Thematic Miniseries on NAFLD-derived HCC Source Type: research
This study was undertaken to investigate the characteristics and survival course of this patient group.METHODS: We retrospectively analyzed the database of patients with HCC at a tertiary center during a 10-year period (2009-2019). All demographic, clinical, laboratory, and tumoral features with survival outcomes were compared between the HCC-CL and HCC-NCL groups.RESULTS: Out of 384 HCC cases, 11.2% (n = 43) had no cirrhosis. The dominant etiology in the HCC-NCL group was hepatitis B virus (n = 26, 60.5%), followed by non-alcoholic fatty liver disease (n = 10, 23.2%), and hepatitis C virus (n = 7, 16.3%). The maximum tumo...
Source: The Turkish Journal of Gastroenterology - Category: Gastroenterology Authors: Source Type: research
CONCLUSION: Polyphenols are relevant bioactive compounds in terms of prevention and treatment of NAFLD, which exhibit low bioavailability and instability in biological systems that could limit their health effects. These drawbacks reinforce the necessity of further studies to improve the efficacy of polyphenol formulations for human interventions.PMID:34525916 | DOI:10.2174/0929867328666210825111350
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Source Type: research
This study was undertaken to investigate the characteristics and survival course of this patient group.METHODS: We retrospectively analyzed the database of patients with HCC at a tertiary center during a 10-year period (2009-2019). All demographic, clinical, laboratory, and tumoral features with survival outcomes were compared between the HCC-CL and HCC-NCL groups.RESULTS: Out of 384 HCC cases, 11.2% (n = 43) had no cirrhosis. The dominant etiology in the HCC-NCL group was hepatitis B virus (n = 26, 60.5%), followed by non-alcoholic fatty liver disease (n = 10, 23.2%), and hepatitis C virus (n = 7, 16.3%). The maximum tumo...
Source: The Turkish Journal of Gastroenterology - Category: Gastroenterology Authors: Source Type: research
Biochem Pharmacol. 2021 Sep 13:114764. doi: 10.1016/j.bcp.2021.114764. Online ahead of print.ABSTRACTChronic liver disease (CLD) is considered the leading cause of global mortality. In westernized countries, increased consumption of alcohol and overeating foods with high fat/ high glucose promote progression of CLD such as alcoholic liver disease (ALD) and non-alcoholic liver disease (NAFLD). Accumulating evidence and research suggest that ubiquitin, a 75 amino acid protein, plays crucial role in the pathogenesis of CLD through dynamic post-translational modifications (PTMs) exerting diverse cellular outcomes such as prote...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research
CONCLUSION: Polyphenols are relevant bioactive compounds in terms of prevention and treatment of NAFLD, which exhibit low bioavailability and instability in biological systems that could limit their health effects. These drawbacks reinforce the necessity of further studies to improve the efficacy of polyphenol formulations for human interventions.PMID:34525916 | DOI:10.2174/0929867328666210825111350
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Source Type: research
Animal experimentation is limited by unethical procedures, time-consuming protocols, and high cost. Thus, the development of innovative approaches for disease treatment based on alternative models in a fast, safe, and economic manner is an important, yet challenging goal. In this paradigm, the fruit-fly Drosophila melanogaster has become a powerful model for biomedical research, considering its short life cycle and low-cost maintenance. In addition, biological processes are conserved and homologs of ∼75% of human disease-related genes are found in the fruit-fly. Therefore, this model has been used in innovative approac...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
g Il Lee Seung Up Kim Non-alcoholic fatty liver disease (NAFLD) is associated with an increased hepatocellular carcinoma (HCC) risk. We established and validated a liver stiffness (LS)-based risk prediction model for HCC development in patients with NAFLD. A total of 2666 and 467 patients with NAFLD were recruited in the training and validation cohorts, respectively. NAFLD was defined as controlled attenuated parameter ≥238 dB/m by transient elastography. Over a median of 64.6 months, HCC developed in 22 (0.8%) subjects in the training cohort. Subjects who developed HCC were older and had higher prevalence of diab...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Exp Cell Res. 2021 Aug 24:112787. doi: 10.1016/j.yexcr.2021.112787. Online ahead of print.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) and its more advanced stages, Non-alcoholic steatohepatitis and Cirrhosis, are the most common liver diseases in the worldwide, especially in developing countries. NAFLD is distinguished by the accumulation of triglycerides within hepatocytes. An increasing body of evidence suggests that hepatic MicroRNAs play an important role in NAFLD by controlling lipid metabolism, inflammation, and fibrosis. However, the precise causative functions of miRNA in NAFLD remain unknown. Here, we discov...
Source: Experimental Cell Research - Category: Cytology Authors: Source Type: research
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