scholarly journals The impact of PNPLA3 and TM6SF2 in cirrhosis related complications

2021 ◽  
Author(s):  
Haruki Uojima ◽  
Xue Shao ◽  
Taeang Arai ◽  
Yuji ogawa ◽  
Toru Setsu ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Hepatic Encephalopathy ◽  
Odds Ratio ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Fibrosis Progression ◽  
Cirrhotic Patients ◽  
The Impact

Patatin-like phospholipase domain-containing 3 (PNPLA3) and transmembrane 6-superfamily member 2 (TM6SF2) polymorphisms have major impact for fibrosis due to steatohepatitis. However, there are scant data about correlations between cirrhosis-related complications and the polymorphisms of these genes. Therefore, we aimed to determine the role of the PNPLA3 and TM6SF2 polymorphisms in fibrosis progression for patients with liver cirrhosis. A multicenter study was performed at six hospitals in Japan enrolling 400 patients with liver cirrhosis caused by virus (n = 157), alcohol (n = 104), nonalcoholic fatty liver disease (NAFLD) (n = 106), or autoimmune disease (n = 33). These cirrhotic patients included those with complications of variceal bleeding, hepatic ascites, and/or hepatic encephalopathy and those without. To assess the role of the PNPLA3 and TM6SF2 polymorphisms in patients with cirrhosis related complications, we calculated the odds ratio and relative risk for the rs738409 and rs58542926 polymorphisms. We also accessed whether or not the interaction between these two polymorphisms contributed to cirrhosis related complications. As a result, the odds ratio for complications in the NAFLD group significantly increased in the presence of the rs738409 GG genotype when the CC genotype was used as the reference. There were no significant risks between complications and the presence of the rs738409 G allele in the virus or alcohol groups. There were no significant risks of complications in the frequency of the rs58542926 T polymorphism regardless of the etiology of liver cirrhosis. The interaction between the trs738409 and rs58542926 polymorphisms had the highest odds ratio of 2.415 for complications in the rs738409 GG + rs58542926 (CT+TT) group when rs738409 (CC+CG) + TM6SF2 CC was used as the reference in the NAFLD group.

scholarly journals The risk of cirrhosis and its complications based on PNPLA3 rs738409 G allele frequency

2021 ◽  
Author(s):  
Xue Shao ◽  
Haruki Uojima ◽  
Taeang Arai ◽  
Yuji Ogawa ◽  
Toru Setsu ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Hepatic Encephalopathy ◽  
Odds Ratio ◽  
Fatty Liver Disease ◽  
Wild Type ◽  
Nonalcoholic Fatty Liver ◽  
Entire Cohort ◽  
Significant Difference ◽  
Background Data

Background: Data regarding the influence of patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism for patients with liver cirrhosis (LC) are scarce. Objective: This study assesses the role of the PNPLA3 polymorphism for the development of LC and its complications by the findings of genetic examinations. Methods: Patients with LC caused by virus (n = 157), alcohol (n = 104), nonalcoholic fatty liver disease (NAFLD) (n = 106), or autoimmune disease (n = 33) and without LC (n = 128) were enrolled. LC were composed of the present and absent of complications, such as variceal bleeding, hepatic ascites, and/or hepatic encephalopathy. To assess the role of the PNPLA3 polymorphism, odds ratio (OR) for the rs738409 variant was calculated for the patients between (i) with LC and without LC in the entire cohort, and (ii) the present and absent of complications in the patients with LC. Results: There was a significant difference among the patients without LC and those with alcohol, NAFLD related LC in the frequency of G alleles (p < 0.001, both). According to complications of LC, the OR for NAFLD related cirrhosis significantly increased in the presence of the two mutated alleles (OR = 3.165; p = 0.046) when the wild type was used as the reference. However, there were no significant risks for the complications in the virus and alcohol related cirrhosis unless there was a presence of G alleles. Conclusion: The PNPLA3 polymorphism was associated with the risk of NAFLD related LC and its complications.

scholarly journals Up-Regulated MicroRNA-27b Promotes Adipocyte Differentiation via Induction of Acyl-CoA Thioesterase 2 Expression

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Yuka Murata ◽  
Takashi Yamashiro ◽  
Takaomi Kessoku ◽  
Israt Jahan ◽  
Haruki Usuda ◽  
...  
Keyword(s):  
Liver Disease ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Adipocyte Differentiation ◽  
Aberrant Expression ◽  
Nonalcoholic Fatty Liver ◽  
Important Pathway ◽  
The Impact ◽  
Intracellular Triglyceride

Nonalcoholic fatty liver disease (NAFLD) is characterized by a spectrum of liver pathologies, from simple steatosis to steatohepatitis. Recent studies have increasingly noted the aberrant expression of microRNAs closely related to NAFLD pathologies. We have previously shown the presence of increased levels of microRNA-27b (miR-27b) in patients with NAFLD. In this study, we investigated the role of miR-27b in NAFLD by examining the impact of up-regulated miR-27b on the differentiation of preadipocytes into mature adipocytes. We found that miR-27b-3p remarkably enhances the adipocyte differentiation of 3T3-L1 cells associated with lipid accumulation and intracellular triglyceride contents. Furthermore, we have demonstrated not only that miR-27b-3p induces acyl-CoA thioesterase 2 (ACOT2) expression in 3T3-L1 cells, but also that the knockdown of ACOT2 suppresses lipid accumulation and adipocyte differentiation in both the presence and absence of miR-27b-3p treatment. Our data strongly suggest that the miR-27b-ACOT2 axis is an important pathway in adipocyte differentiation and may play a role in the pathogenesis of NAFLD.

scholarly journals Role of gut microbiota in liver disease

2020 ◽  
Vol 318 (1) ◽  
pp. G84-G98 ◽  
Author(s):  
Somaya A. M. Albhaisi ◽  
Jasmohan S. Bajaj ◽  
Arun J. Sanyal
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Fatty Liver Disease ◽  
Biological Functions ◽  
Nonalcoholic Fatty Liver ◽  
Major Player ◽  
Normal Composition

The gut microbiome is the natural intestinal inhabitant that has been recognized recently as a major player in the maintenance of human health and the pathophysiology of many diseases. Those commensals produce metabolites that have various effects on host biological functions. Therefore, alterations in the normal composition or diversity of microbiome have been implicated in various diseases, including liver cirrhosis and nonalcoholic fatty liver disease. Moreover, accumulating evidence suggests that progression of dysbiosis can be associated with worsening of liver disease. Here, we review the possible roles for gut microbiota in the development, progression, and complication of liver disease.

scholarly journals Role of perilipins in the development of fatty liver disease.

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Erica Kubascik ◽  
Madison DeGoey ◽  
Dr. Gupta ◽  
Dr. Kostrominova
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Intracellular Distribution ◽  
Nonalcoholic Fatty Liver ◽  
Intracellular Receptor ◽  
The Impact ◽  
Oligomerization Domain

Background and Hypothesis: Lipid droplets (LDs) are fatty acid (FA) containing structures within cells. In obesity, hepatic LDs accumulate more FA which may cause steatosis and nonalcoholic fatty liver disease (NAFLD). Perilipins (PLINs) are a family of LDassociated proteins involved in intracellular trafficking and signaling. In hepatocytes, NAFLD alters expression of PLINs. Using metabolomics, Dr. Gupta’s laboratory previously showed enlarged LDs and altered PLIN1, 3, and 4 content in NOD2-/- compared to wild type (WT) mice on high fat diet (HFD). Nucleotide-binding and oligomerization domain (NOD) is an intracellular receptor that regulates sensitivity to obesity. To expand on Dr. Gupta’s study, we quantified diet-induced alterations and visualized intracellular distribution of PLINs in mouse livers. We hypothesized that PLIN2, 3, and 4 concentrations would increase whereas PLIN1 would decrease in NOD2-/-HFD compared to WTHFD mice. Methods: Immunostaining was used to visualize intracellular distribution of PLINs. Western blotting was used to quantify differences in PLINs protein expression.  Results: LD distribution showed WT regular chow (RC) = NOD2-/-RC < WTHFD<<NOD2-/-HFD. Bright LD-associated staining for PLIN2 was observed in both small and large LDs in all four groups. PLIN3 brightly stained the bile ducts, and it stained small LDs but not large LDs. PLIN4 stained small intracellular LDs in all four groups. PLIN1 showed a trend for decrease in both NOD2-/-HFD and WTHFD compared with RC mice. PLIN2 appears to be decreased in WTHFD and both NOD2-/- groups compared to WTRC. PLIN3 seemed to show increased expression in WTHFD but not in NOD2-/-. PLIN4 showed a trend for decreased expression in both NOD2-/-RC and NOD2-/-HFD mice compared to WTRC. Conclusion: Despite enlarged LD size, there was no detectable increase in PLINs expression in NOD2-/-HFD compared to WTHFD. This may be due to the impact of other LDassociated proteins in the livers of NOD2-/- mice.

scholarly journals Nonalcoholic fatty liver disease and the risk of atrial fibrillation stratified by body mass index: a nationwide population-based study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
So-Ryoung Lee ◽  
Kyung-Do Han ◽  
Eue-Keun Choi ◽  
Seil Oh ◽  
Gregory Y. H. Lip
Keyword(s):  
Atrial Fibrillation ◽  
Body Mass Index ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Body Mass ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Increased Risk ◽  
The Impact

AbstractWe evaluated the association between nonalcoholic fatty liver disease (NAFLD) and incident atrial fibrillation (AF) and analyzed the impact of NAFLD on AF risk in relation to body mass index (BMI). A total of 8,048,055 subjects without significant liver disease who were available fatty liver index (FLI) values were included. Subjects were categorized into 3 groups based on FLI: < 30, 30 to < 60, and ≥ 60. During a median 8-year of follow-up, 534,442 subjects were newly diagnosed as AF (8.27 per 1000 person-years). Higher FLI was associated with an increased risk of AF (hazard ratio [HR] 1.053, 95% confidence interval [CI] 1.046–1.060 in 30 ≤ FLI < 60, and HR 1.115, 95% CI 1.106–1.125 in FLI ≥ 60). In underweight subjects (BMI < 18.5 kg/m2), higher FLI raised the risk of AF (by 1.6-fold in 30 ≤ FLI < 60 and by twofold in FLI ≥ 60). In normal- and overweight subjects, higher FLI was associated with an increased risk of AF, but the HRs were attenuated. In obese subjects, higher FLI was not associated with higher risk of AF. NAFLD as assessed by FLI was independently associated with an increased risk of AF in nonobese subjects with BMI < 25 kg/m2. The impact of NAFLD on AF risk was accentuated in lean subjects with underweight.

scholarly journals Role of Docosahexaenoic Acid Treatment in Improving Liver Histology in Pediatric Nonalcoholic Fatty Liver Disease

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e88005 ◽  
Author(s):  
Valerio Nobili ◽  
Guido Carpino ◽  
Anna Alisi ◽  
Rita De Vito ◽  
Antonio Franchitto ◽  
...  
Keyword(s):  
Liver Disease ◽  
Docosahexaenoic Acid ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Acid Treatment ◽  
Liver Histology ◽  
Nonalcoholic Fatty Liver

scholarly journals Role of folate in nonalcoholic fatty liver disease

2017 ◽  
Vol 95 (10) ◽  
pp. 1141-1148 ◽  
Author(s):  
Victoria Sid ◽  
Yaw L. Siow ◽  
Karmin O
Keyword(s):  
Type 2 Diabetes ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Serum Folate ◽  
Nonalcoholic Fatty Liver ◽  
Obesity And Diabetes

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver conditions that are characterized by steatosis, inflammation, fibrosis, and liver injury. The global prevalence of NAFLD is rapidly increasing in proportion to the rising incidence of obesity and type 2 diabetes. Because NAFLD is a multifaceted disorder with many underlying metabolic abnormalities, currently, there is no pharmacological agent that is therapeutically approved for the treatment of this disease. Folate is a water-soluble B vitamin that plays an essential role in one-carbon transfer reactions involved in nucleic acid biosynthesis, methylation reactions, and sulfur-containing amino acid metabolism. The liver is the primary organ responsible for storage and metabolism of folates. Low serum folate levels have been observed in patients with obesity and diabetes. It has been reported that a low level of endogenous folates in rodents perturbs folate-dependent one-carbon metabolism, and may be associated with development of metabolic diseases such as NAFLD. This review highlights the biological role of folate in the progression of NAFLD and its associated metabolic complications including obesity and type 2 diabetes. Understanding the role of folate in metabolic disease may position this vitamin as a potential therapeutic for NAFLD.

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