Obesity-linked suppression of membrane-bound O -Acyltransferase 7 (MBOAT7) drives non-alcoholic fatty liver disease

Recent studies have identified a genetic variant rs641738 near two genes encoding membrane boundO-acyltransferase domain-containing 7 (MBOAT7) and transmembrane channel-like 4 (TMC4) that associate with increased risk of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related cirrhosis, and liver fibrosis in those infected with viral hepatitis1-7. Based on hepatic expression quantitative trait loci analysis it has been suggested thatMBOAT7 loss of function promotes liver disease progression1-7, but this has never been formally tested. Here we show thatMboat7 loss, but notTmc4, in mice is sufficient to promote the progression of NAFLD in the setting of high fat diet.Mboat7 loss of function is associated with accumulation of its substrate lysophosphatidylinositol (LPI) lipids, and direct administration of LPI promotes hepatic inflammatory and fibrotic transcriptional changes in anMboat7-dependent manner. These studies reveal a novel role for MBOAT7-driven acylation of LPI lipids in suppressing the progression of NAFLD.
Source: eLife - Category: Biomedical Science Tags: Human Biology and Medicine Source Type: research

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This article reviews the most updated information about NAFLD-related HCC and provides some insight into strategies that must be considered to reduce its potential disease burden.
Source: Hepatology International - Category: Infectious Diseases Source Type: research
The objective of the present study was to gain deeper knowledge about the metabolic processes involved in the NASH animal model, and particularly in the effect of PH by using metabolomics. For achieving such information, twelve 8-week-old male C57BL/6 J mice, fed commercial chow (control diet) or methionine and choline-Deficient diet (MCD) for three weeks were subjected to PH and sacrificed 2 weeks later. Livers were removed and submitted to metabolic profiling analysis through RP-LC/MS (qTOF), GC/MS (qTOF) and CE/MS(TOF). More than 3000 different features were detected and repeated measurements one-way ANOVA analys...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research
Conclusions: The constantly increasing prevalence of NAFLD in the general population can contribute to a growing role of NAFLD/NASH in HCC epidemiology. Moreover, some particular challenges specific for patients with liver steatosis may impede proper HCC diagnosis, treatment and follow-up. PMID: 31631714 [PubMed - as supplied by publisher]
Source: Current Medical Research and Opinion - Category: Research Tags: Curr Med Res Opin Source Type: research
idinis Liver cancer is one of the leading causes of death worldwide due to late diagnosis and scarcity of treatment options. The major risk factor for liver cancer is cirrhosis with the underlying causes of cirrhosis being viral infection (hepatitis B or C), metabolic deregulation (Non-alcoholic fatty liver disease (NAFLD) in the presence of obesity and diabetes), alcohol or cholestatic disorders. Lysophosphatidic acid (LPA) is a bioactive phospholipid with numerous effects, most of them compatible with the hallmarks of cancer (proliferation, migration, invasion, survival, evasion of apoptosis, deregulated metabolism, ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Authors: Marjot T, Moolla A, Cobbold JF, Hodson L, Tomlinson JW Abstract Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease, extending from simple steatosis, through to inflammation and fibrosis with a significant risk for the development of cirrhosis. It is highly prevalent and is associated with significant adverse outcomes both through liver-specific morbidity and mortality, but perhaps more importantly, through adverse cardiovascular and metabolic outcomes. It is tightly associated with type 2 diabetes and obesity and both of these conditions drive progressive disease towards the more advanced s...
Source: Endocrine Reviews - Category: Endocrinology Tags: Endocr Rev Source Type: research
(NAFLD) is a global health problem, with an estimated prevalence of 30% among adults in industrialized countries, and associated with obesity and type 2 diabetes mellitus. NAFLD is defined histologically and represents a spectrum from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Hepatic triglyceride droplet accumulation is considered the first feature in the natural history; in some patients, this is associated with inflammation and fibrosis, through the interaction of environmental and host factors.
Source: Medicine - Category: Internal Medicine Authors: Tags: Common european liver disorders Source Type: research
CONCLUSION: Despite some limitations of our study, such as the small number of patients, and the use of two different methods of evaluation (biopsy and elastography), the data obtained allow us to conclude that of the 39 evaluated cases, 33% (13) presented progression of fibrosis and the total group of 50 patients, 42% had cirrhosis or died due to liver disease. The presence of NASH on hepatic biopsy did not prove to be, in our study, a predictive of the evolution of hepatic fibrosis in the patients.RESUMO CONTEXTO: A doen ça hepática gordurosa não alcoólica vem sendo diagnosticada com frequ&eci...
Source: Arquivos de Gastroenterologia - Category: Gastroenterology Source Type: research
Non-alcoholic fatty liver disease (NAFLD) is a growing challenge to global public health. It is defined as the increased accumulation of hepatic triglyceride (>5%) in the absence of excessive alcohol consumption or other causes of liver disease. The NAFLD spectrum encompasses steatosis (non-alcoholic fatty liver, NAFL) and non-alcoholic steatohepatitis (NASH), an inflammatory form of the condition marked by the presence of hepatocyte damage and progressive fibrosis that may lead to cirrhosis.[1,2] Although NAFLD may occur in patients with normal weight, it is closely associated with the presence of the metabolic syndrom...
Source: Journal of Hepatology - Category: Gastroenterology Authors: Source Type: research
Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the leading liver diseases worldwide. NAFLD is characterised by hepatic steatosis and may progress to an inflammatory condition termed non-alcoholic steatohepatitis, (NASH), liver cirrhosis and hepatocellular carcinoma. It became evident in the last years that NAFLD pathophysiology is complex and involves diverse immunological and metabolic pathways. An association between intestinal signals (e.g. derived from the gut microbiota) and the development of obesity and its metabolic consequences such as NAFLD are increasingly recognized. Preclinical studies have sh...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Publication date: Available online 3 September 2019Source: Redox BiologyAuthor(s): Mi Hye Kim, Jung Bae Seong, Jae-Won Huh, Yong Chul Bae, Hyun-Shik Lee, Dong-Seok LeeAbstractNon-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease globally. NAFLD—which can develop into liver fibrosis, nonalcoholic steatohepatosis, cirrhosis, and hepatocellular carcinoma—is defined as an excess accumulation of fat caused by abnormal lipid metabolism and excessive reactive oxygen species (ROS) generation in hepatocytes. Recently, we reported that Peroxiredoxin 5 (Prx5) plays an essential role i...
Source: Redox Biology - Category: Biology Source Type: research
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