Simple Nonalcoholic Fatty Liver Research Articles

Nonalcoholic fatty liver disease test: an external validation cohort

PurposeNon-invasive diagnosis of nonalcoholic fatty liver disease (NAFLD) and its advanced phenotypes (e.g., nonalcoholic steatohepatitis; NASH) is a hot research topic. The aim of this report was the validation of a novel non-invasive index of NAFLD, the “NAFLD test,” recently introduced for the diagnosis of NAFLD (vs. non-NAFLD controls).MethodsThis was a post-hoc analysis of a previous study. The NAFLD test was calculated in NAFLD patients and non-NAFLD controls; the performance of the test was compared with that of other non-invasive indices of NAFLD (fatty liver index [FLI] and hepatic steatosis index [HSI]), and other indices of NASH (index of NASH [ION] and cytokeratin-18/homeostasis model assessment-insulin resistance/aspartate transaminase index [CHAI]).ResultsThe NAFLD test was higher in NAFLD patients than in controls (1.89 ± 0.14 vs. 1.30 ± 0.06, respectively; p < 0.001). In NAFLD patients, the NAFLD test was higher in NASH patients than in those with simple nonalcoholic fatty liver (NAFL) (2.21 ± 0.24 vs. 1.57 ± 0.08, respectively; p = 0.007). The area under the receiver operating characteristic curve (AUC) of the NAFLD test was 0.84 (95% CI: 0.74–0.94; p < 0.001) for differentiation between NAFLD and non-NAFLD controls and its performance was similar to that for FLI and HSI. For differentiation between NASH and NAFL patients, the AUC of the NAFLD test was 0.88 (95% CI: 0.62–0.96; p = 0.007) and its performance was superior to that for ION and CHAI.ConclusionsThe NAFLD test was validated in this external cohort for the non-invasive diagnosis of NAFLD patients vs. non-NAFLD individuals. It was also shown to differentiate between NASH and NAFL patients with acceptable accuracy.

Curcumin protects against high-fat diet-induced nonalcoholic simple fatty liver by inhibiting intestinal and hepatic NPC1L1 expression via down-regulation of SREBP-2/HNF1α pathway in hamsters

Niemann-pick C1-like 1 (NPC1L1) mediates cholesterol absorption and plays a key role in the pathogenesis of nonalcoholic simple fatty liver (NASFL). Our previous study showed that curcumin reduced NPC1L1 expression and cholesterol absorption in Caco-2 cells. This study aimed to investigate whether curcumin could inhibit intestinal and hepatic NPC1L1 expression through suppressing sterol regulatory element binding protein-2 (SREBP-2) / hepatocyte nuclear factor 1α (HNF1α) pathway, then exert anti-NASFL effects. Six-week hamsters were fed high-fat diet (HFD) with or without 0.1% curcumin for 12 weeks. Curcumin supplementation lowered blood total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol levels (20.2%, 48.7%, and 36.5%), and reduced liver TC and TG contents (26.1% and 26.5%). Oil Red O staining demonstrated that curcumin significantly alleviated HFD-induced liver fat accumulation and hepatic steatosis, which was accompanied by reduced intestinal and hepatic NPC1L1, SREBP-2 and HNF1α expression (P < .05) and increased fecal neutral sterol excretion (114.5%). Furthermore, curcumin decreased cholesterol absorption in Caco-2 cells and HepG2 cells (49.2 % and 52.7 %). The inhibitory effects of curcumin on NPC1L1 expression and cholesterol absorption could be prevented by blockade of the SREBP-2 and HNF1α pathway. These findings indicated that curcumin protected against HFD-induced NASFL by inhibiting intestinal and hepatic NPC1L1 expression via down-regulation of SREBP-2/HNF1α pathway, thus reducing intestinal cholesterol absorption and hepatic biliary cholesterol reabsorption, consequently alleviating liver cholesterol accumulation and steatosis. Our study provides evidence for curcumin as a potential nutritional therapy for NASFL by regulating NPC1L1 and enterohepatic circulation of cholesterol.

Current insights in molecular characterization of non-alcoholic fatty liver disease and treatment.

There is a continuously rising incidence of non-alcoholic fatty liver disease (NAFLD) around the world, which parallels the increasing incidence of metabolic diseases. NAFLD is a range of liver conditions that contains simple non-alcoholic fatty liver and advanced non-alcoholic steatohepatitis. In serious cases, NAFLD may develop into cirrhosis or even liver cancer. NAFLD has an intense relationship with metabolic syndrome, type 2 diabetes mellitus. It is known that gut microbiota, and functional molecules such as adenosine monophosphate-activated protein kinase JNK, and peroxisome proliferator-activated receptors (PPARs) in progressing and treating NAFLD. Traditionally, the conventional and effective therapeutic strategy is lifestyle intervention. Nowadays, new medicines targeting specific molecules, such as farnesoid X receptor, PPARs, and GLP-1 receptor, have been discovered and shown beneficial effects on patients with NAFLD. In this article, we focus on the molecular mechanisms and therapeutic approaches to NAFLD.

Change lifestyle modification plan/transtheoretical model in non-alcoholic simple fatty liver disease: a pilot randomized study

BackgroundNon-alcoholic simple fatty liver disease patients have very low compliance with almost all types of physical activities. A transtheoretical model-oriented lifestyle modification plan awakens the patient’s consciousness in the pre-intention stage. Aim to evaluate whether a management by stages of change plan based on the Transtheoretical Model and Stages of Change promoted behavior change for patients with non-alcoholic simple fatty liver disease.MethodsPatients with simple fatty liver diagnosed from July to December 2019 were randomly divided into the transtheoretical model and non-transtheoretical model groups. Primary outcome was change in health belief and health behavior based on questionnaires. Secondary outcomes included changes in blood lipids, body mass indexes, and waist circumference 12-months after intervention.ResultsOf 200 enrolled patients 194 were analyzed (non-transtheoretical model group n = 98, transtheoretical model group n = 96). After intervention, total health belief scores (120.91 ± 4.94 vs. 118.82 ± 5.48) and total health behavior scores (131.71 ± 5.87 vs. 119.96 ± 7.12) were higher in the transtheoretical model group (all P < 0.05). Blood lipids, body mass index, and waist circumference more obviously improved in the transtheoretical model group (all P < 0.05).ConclusionA transtheoretical model-based lifestyle modification intervention can be effectively applied to patients with non-alcoholic simple fatty liver.Clinical Research Registration NumberChiCTR2100049354. The registration date is August 1, 2021.

Nonalcoholic Steatohepatitis Diagnosis - A Model-Related Personalized Medicine Approach.

Nonalcoholic fatty liver disease (NAFLD) is a clinical syndrome, and pathologically characterized by diffuse macro-vesicular fatty change in the hepatocytes. NAFLD includes simple nonalcoholic fatty liver disease, nonalcoholic steatohepatitis (NASH) and hepatic cirrhosis. NASH is a disease evolving under the influence of various stimuli still poorly understood, but where insulin resistance is prominently. In this paper, we present a new diagnosis model to predict NASH.

Analysis of hub genes and molecular mechanisms in non-alcoholic steatohepatitis based on the gene expression omnibus database

Objective: To explore the hub genes and mechanisms in the pathological process of non-alcoholic steatohepatitis (NASH) by bioinformatics methods. Methods: Microarray datasets GSE89632 were downloaded from the Gene Expression Omnibus (GEO) database, which including 20 simple non-alcoholic fatty liver disease patients, 19 NASH patients and 24 healthy control individuals. The differentially expressed genes (DEGs) in patients with simple non-alcoholic fatty liver disease and NASH were compared with healthy control individuals respectively, and the intersection of the two groups of DEGs was taken. GO functional annotation and KEGG pathway enrichment analysis of DEGs were performed with DAVID 6.8 and KOBAS 3.0 separately. Protein-protein interaction network (PPI) was constructed by STRING database, then the mRNA hub genes were selected by Cytoscape software. The Attie Lab Diabetes database was used to verify the relative expression of hub genes mRNA in the liver of 4 groups of C57BL/6 mice (4-week-old normal group, 4-week-old obese group, 10-week-old normal group and 10-week-old obese group, 5 mice in each group). Spearman's correlation analysis was performed to analyze the correlation between hub gens and prognostic clinical parameters. Results: From the GSE89632 dataset, 365 common DEGs (115 up-regulated genes and 250 down-regulated genes) were identified in patients with simple non-alcoholic fatty liver disease and NASH patients compared with control individuals. GO analysis showed that DEGs were mainly enriched in biological processes such as inflammatory response and immune response. KEGG pathway analysis showed that up-regulated genes were mainly enriched in cholesterol metabolism, bile secretion and fat digestion and absorption signal pathways. Down-regulated genes were mainly enriched in interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, advanced glycation end products and their receptors of diabetic complications. Seven key hub genes were identified by PPI analysis, which were FOS, EGR1, FOSB, JUNB, FOSL1, MYC and NR4A1.The mRNA relative expression levels of EGR1 and JUNB in the liver of 10-week-old obese mice were lower than those of normal mice (P<0.05).The relative expression levels of NR4A1 in the liver of obese mice at 4-and 10-week-old were lower than those of normal mice at the same age (P values<0.05). Spearman's correlation analysis showed that the expression of EGR1 was negatively correlated with the degree of hepatic steatosis (r=-0.785, P<0.001).The expression levels of FOSB, MYC and NR4A1 were negatively correlated with the level of alanine aminotransferase (r=-0.649, -0.597 and-0.580 respectively, all P values<0.001). Conclusion: EGR1, FOSB, MYC, JUNB and NR4A1 might be the hub genes in the pathological process of NASH and the inflammatory and immune response in hepatocytes, IL-17 signaling pathway and TNF signaling pathway might be the key molecular mechanisms in the occurrence and development of NASH.

Flaxseed Powder Attenuates Non-Alcoholic Steatohepatitis via Modulation of Gut Microbiota and Bile Acid Metabolism through Gut-Liver Axis.

Non-alcoholic steatohepatitis (NASH) is gradually becoming one of the most common and health-endangering diseases; therefore, it is very important to prevent the occurrence of NASH and prevent simple non-alcoholic fatty liver (NAFL) from further developing into NASH. We fed mice a high-fat diet (HFD, 60% fat) for 14 weeks to induce NAFL and then fed different doses of flaxseed powder (low (10%), middle (20%), and high (30%)) to the mice for 28 weeks. After the animal experiment, we analyzed fecal bile acid (BA) profiles of the HFD mice, flaxseed-fed (FLA-fed) mice, and control mice with a normal diet (10% fat) using a targeted metabolomics approach, and we analyzed the gut microbiota at the same time. We also investigated the mechanistic role of BAs in NASH and identified whether the altered BAs strongly bind to colonic FXR or TGR5. In the present study, we found that 28-week FLA treatment notably alleviated NASH development in NAFL model mice fed with an HFD, and the beneficial effects may be attributed to the regulation of and improvement in the gut flora- and microbiota-related BAs, which then activate the intestinal FXR-FGF15 and TGR5-NF-κB pathways. Our data indicate that FLA might be a promising functional food for preventing NASH through regulating microbiomes and BAs.

Impact of Nonalcoholic Steatohepatitis on the Outcome of Patients Undergoing Roux-en-Y Gastric Bypass Surgery: a Propensity Score\u2013Matched Analysis

PurposeIt is currently unknown whether NASH (nonalcoholic steatohepatitis), as compared to simple steatosis, is associated with impaired postoperative weight loss and metabolic outcomes after RYGB surgery. To compare the effectiveness of Roux-en-Y gastric bypass (RYGB) on patients with NASH versus those with simple nonalcoholic fatty liver (NAFL).Materials and MethodsWe retrospectively retrieved data from 515 patients undergoing RYGB surgery with concomitant liver biopsy. Clinical follow-up and metabolic assessment were performed prior to surgery and 12 months after surgery. We used multivariate analysis of variance (MANOVA) and propensity score matching and we assessed for changes in markers of hepatocellular injury and metabolic outcomes.ResultsThere were 421 patients with simple NAFL, and 94 with NASH. Baseline alanine and aspartate aminotransferases were significantly higher in patients with NASH (p < 0.01). Twelve months after the RYGB surgery, as determined by both MANOVA and propensity score matching, patients with NASH exhibited a significantly greater reduction in alanine aminotransferase (ß-coefficient − 12 iU/l [− 22 to − 1.83], 95% CI, adjusted p = 0.021) compared to their NAFL counterparts (31 matched patients in each group with no loss to follow-up at 12 months). Excess weight loss was similar in both groups (ß-coefficient 4.54% [− 3.12 to 12.21], 95% CI, adjusted p = 0.244). Change in BMI was comparable in both groups (− 14 (− 16.6 to − 12.5) versus − 14.3 (− 17.3 to − 11.9), p = 0.784).ConclusionAfter RYGB surgery, patients with NASH experience a greater reduction in markers for hepatocellular injury and similar weight loss compared to patients with simple steatosis.

Impact of Non-Alcoholic Simple Fatty Liver Disease on Antituberculosis Drug-Induced Liver Injury.

ObjectiveTo observe the effect of non-alcoholic simple fatty liver disease on drug-induced liver injury caused by tuberculosis.MethodsWe retrospectively analyzed the incidence, characteristics, and risk factors of antituberculosis drug-induced liver injury in 104 patients with initial treatment of tuberculosis complicated with non-alcoholic simple fatty liver disease. The patients were divided into two groups according to whether there was liver injury or not. The differences in age, gender, body mass index (BMI), cholesterol, and triglycerides were studied between the two groups.ResultsAmong the 104 patients with initial treatment of tuberculosis complicated with non-alcoholic fatty liver disease, 24 (23%) patients developed a drug-induced liver injury. The remaining 80 (77%) patients did not develop drug-induced liver injury (χ2 = 60.308, P < 0.05). In the liver injury group, there were 20 cases of mild liver injury, two cases of moderate liver injury, two cases of severe liver injury, 22 cases of hepatocellular injury, two cases of cholestasis, and no cases of mixed liver injury. The time of abnormal liver function in antituberculosis treatment was 16.42 ± 9.18 days from the beginning of the antituberculosis treatment. There were no significant differences in gender, age, BMI, or triglyceride between the liver injury group and the non-liver injury group (χ2 = 2.063, t = 0.179, t = 0.703, t = 1.12, P > 0.05 in all), but there were significant differences in cholesterol (t = 3.08, P < 0.05). By logistic regression analysis, cholesterol was a high-risk factor for liver injury.ConclusionNon-alcoholic simple fatty liver disease may increase the risk of antituberculosis drug-induced liver injury.

Clinical Effect of Dyspepsia-Relieving and Liver-Nourishing Granule on Damp-Heat Blocking Syndrome Non-Alcoholic Simple Fatty Liver

Clinical Effect of Dyspepsia-Relieving and Liver-Nourishing Granule on Damp-Heat Blocking Syndrome Non-Alcoholic Simple Fatty Liver

LncRNA-Gm9795 promotes inflammation in non-alcoholic steatohepatitis via NF-kappa {}B/JNK pathway by endoplasmic reticulum stress

BackgroundNon-alcoholic steatohepatitis (NASH) is a key stage in leading development of non-alcoholic simple fatty liver (NAFL) into cirrhosis and even liver cancer. This study aimed at exploring the lncRNAs expression profile in NASH and the biological function of a novel LncRNA-gm9795.MethodsMicroarray analysis was performed to compare the expression profiles of lncRNAs in the liver of NASH, NAFLD and normal mice (5 mice for each group). Methionine-choline-deficient Medium (MCD) with Lipopolysaccharide (LPS) or palmitic acid (PA)were used to built NASH cell models. The role and mechanism of LncRNA-gm9795 in NASH were explored by knocking down or over-expressing its expression.ResultsA total of 381 lncRNAs were found to be not only highly expressed in NAFLD, but also is going to go even higher in NASH. A novel LncRNA-gm9795 was significantly highly expressed in liver tissues of NASH animal models and NASH cell models. By staining with Nile red, we found that gm9795 did not affect the fat accumulation of NASH. However, gm9795 in NASH cell models significantly promoted the expression of TNF alpha {}, IL-6, IL-1beta {}, the important inflammatory mediators in NASH. At the same time, we found that gm9795 upregulated the key molecules in endoplasmic reticulum stress (ERS), while NF-kappa {}B/JNK pathways were also activated. When ERS activator Thapsigargin (TG) was introduced in cells with Ggm9757 si-RNA, NF-kappa {}B and JNK pathways were activated. Conversely, ERS inhibitor Tauroursodeoxycholic acid (TUDCA) inhibited NF-kB and JNK pathways in cells with gm9795 overexpression plasmid.ConclusionLncRNA-gm9795 promotes inflammatory response in NASH through NF-kB and JNK pathways by ERS, which might provide theoretical basis for revealing the pathogenesis of NASH and discovering new therapeutic targets

A network pharmacology approach: Inhibition of the NF-κB signaling pathway contributes to the NASH preventative effect of an Oroxylum indicum seed extract in oleic acid-stimulated HepG2 cells and high-fat diet-fed rats

BackgroundThe incidence of nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), has significantly increased in recent years and has become an important public health issue. However, no U.S. Food and Drug Administration (FDA)-approved first-line drug is currently available for the treatment of NAFLD and NASH; therefore, research on new drugs is currently a hot topic. Oroxylum indicum (Linn.) Kurz is extensively distributed in South China and South Asia and has many biological activities. However, its effects on NAFLD or even NASH and the corresponding mechanisms are still not clear. PurposeTo investigate the effect and mechanism of O. indicum seed extract (OISE) on preventing anti-inflammatory action in the progression from simple nonalcoholic fatty liver (NAFL) to NASH. MethodsA network pharmacology method to construct ingredient-target networks and the protein-protein interaction (PPI) network of OISE in NASH were constructed for topological analyses and hub-target screening. Enrichment analyses were performed to identify the critical biological processes and signaling pathways. Simultaneously, in vitro and in vivo experiments investigated the effect and mechanism of OISE, baicalein, and chrysin on inflammation by biochemical indicator detection, luciferase reporters, pathological staining, and immunoblotting in oleic acid-stimulated HepG2 cells or in high-fat diet-fed rats. ResultsThe network pharmacology showed that OISE prevented the development and progression of NAFL into NASH through various pathways and targets and that the nuclear factor NF-κB (NF-κB) pathway regulated by baicalein and chrysin played an important role in the treatment of NASH. In in vitro experiments, we further showed that OISE and its ingredients, namely, baicalein and chrysin, all improved the inflammatory status in oleic acid-stimulated HepG2 cells, inhibited the nuclear transcriptional activities of NF-κB, increased the IκB level, and decreased the phosphorylation level of NF-κB. Furthermore, in a high-fat diet-induced NASH model in rats, we also showed that OISE prevented the development and progression of NASH by inhibiting the nuclear transcriptional activity of NF-κB. ConclusionOISE suppressed inflammatory responses and prevented the development and progression of NAFL into NASH through inhibition of the nuclear transcriptional activity of NF-κB. OISE may be used to treat NAFLD through many functions, including an increase in insulin sensitivity, a decrease in lipid accumulation in the liver, suppression of inflammation, and clearance of free radicals.

Development of a simple nonalcoholic fatty liver disease scoring system indicative of metabolic risks and insulin resistance.

BackgroundNonalcoholic fatty liver disease (NAFLD) is estimated to affect approximately 30% population worldwide. However, there is yet a basic and generally implementable approach to define individuals at risk for NAFLD estimative of metabolic risk.MethodsTotal of 3,634 general participants without history of liver disease and alcohol consumption who received the Korean National Health and Nutrition Examination Survey between 2008 and 2010 were studied. Logistic regression was used to identify significant covariates indicative of NAFLD. Multivariable-adjusted logistic regression was carried out for evaluation on estimative impact of the derived score on metabolic risks.ResultsSex [female; odd ratio (OR), 2.492; 95% confidence interval (CI), 1.921–3.233; P<0.001], waist circumference (WC) (OR, 1.093; 95% CI, 1.077–1.110, P<0.001) systolic blood pressure (OR, 1.033; 95% CI, 1.025–1.040; P<0.001), fasting serum glucose (FSG) (OR, 1.032; 95% CI, 1.026–1.038; P<0.001), triglyceride (OR, 1.007; 95% CI, 1.006–1.009; P<0.001), and alanine aminotransferase (OR, 1.110; 95% CI, 1.097–1.124; P<0.001) were independently indicative of NAFLD, which constituted the derived scoring system. The system revealed a significant correlation with the NAFLD liver fat score, fatty liver index (FLI), body mass index, age, alanine aminotransferase, and triglycerides (BAAT) score, lipid accumulation product, and hepatic steatosis index. In addition, the derived score was significantly estimative of insulin resistance.ConclusionsThe developed score may be supportive of stratification of individuals at high risk of NAFLD, non-invasive fast diagnosis of NAFLD, and estimation of metabolic risk. Future studies that compare the derived score with standard diagnostic tests-validated data, such as ultrasonography of the liver, are needed.

Diagnostic Assessment of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is characterized by fat accumulation at levels exceeding 5% in hepatocytes due to insulin resistance. The disease spectrum ranges from simple nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH)/NASH-related fibrosis or cirrhosis defined by histological findings. Unlike simple NAFL, NASH/NASH-related fibrosis or cirrhosis increases the risk of liver-related morbidity or mortality. Therefore, accurate diagnosis of NASH/NASH-related fibrosis or cirrhosis is needed for management of patients with these diseases. Currently, liver biopsy is the only way to confirm the presence of NASH in an individual with features of NAFLD, but this has some limitations, including sample error, interpretation error, and the invasiveness of the procedure. Therefore, there have been a number of attempts to develop noninvasive methods for differential diagnosis of NASH/NASH-related fibrosis or cirrhosis easily and quickly. Here, we review the assessments for diagnosing NAFLD and the methods for differential diagnosis of NASH/NASH-related fibrosis or cirrhosis.

Microbiota-Associated Therapy for Non-Alcoholic Steatohepatitis-Induced Liver Cancer: A Review.

Even though advancement in medicine has contributed to the control of many diseases to date, cancer therapy continues to pose several challenges. Hepatocellular carcinoma (HCC) etiology is multifactorial. Recently, non-alcoholic fatty liver disease (NAFLD) has been considered as an important risk factor of HCC. NAFLD can be divided into non-alcoholic simple fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) based on histopathological features. Recently, studies have indicated that the gut microbiota is associated with NAFLD and HCC. Therefore, in this review, we have discussed the effects of gut microbiota-related mechanisms, including dysbiosis and gut barrier function, and gut microbiota-derived metabolites on NAFLD and HCC pathogenesis and the potential therapeutic strategies for NAFLD and HCC. With a better understanding of the gut microbiota composition and function, new and improved diagnostic, prognostic, and therapeutic strategies for common liver diseases can be developed.

Lipoprotein A, combined with alanine aminotransferase and aspartate aminotransferase, contributes to predicting the occurrence of NASH: a cross-sectional study

BackgroundNonalcoholic steatohepatitis (NASH) progresses from simple nonalcoholic fatty liver (NAFL) and has a poor prognosis. Abnormal lipid metabolism is closely related to the occurrence and development of nonalcoholic fatty liver disease (NAFLD). This study aimed to study the relationships between serum lipid metabolites and NASH, and to improve the early diagnosis of NASH.MethodsThis study included 86 NAFLD patients (23 NASH and 63 NAFL), and 81 unaffected individuals as controls from West China Hospital between October 2018 and May 2019. With lipid metabolites as the focus of the study, the differences in lipid metabolites were compared between the control group, NAFL patients, and NASH patients. Logistic regression analysis was used to examine the risk factors of NASH. Finally, receiver operating characteristic curve (ROC curve) was used to analyze the efficacy of the metabolites in NASH prediction.ResultsThe levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipoprotein A (LPA) increased with the severity of NAFLD. In NAFLD patients, LPA (OR:1.61; 95%CI: 1.03–2.52) was a potential risk factor for NASH, and ROC analysis showed that the combination of LPA, ALT, and AST had a greater predictive efficiency for NASH.ConclusionsAbnormal apolipoprotein/lipoprotein is closely related to lipid metabolism disorder in patients with NAFLD. In NAFL, the combination of LPA, ALT, and AST contributes to predicting the occurrence of NASH. LPA may be a potential biomarker and therapeutic target for diagnosing and treating NASH.

Estudio descriptivo de la esteatosis hepática y la morbilidad asociada en atención primaria. (Estudio ESTEATOAP)

ObjectiveTo study the recorded prevalence of hepatic steatosis in Primary Care, as well as the proportion of patients diagnosed with fatty liver diseases (FLD) including simple non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) versus steatosis by other causes. In addition, the proportion of cardiometabolic morbidities associated with NAFLD liver was studied. Material and methodsA descriptive observational study was carried out on a population that included all patients with a recorded diagnosis of hepatic steatosis in an urban health centre that serves a population of 25,747 over the age of 14. A sample size of 229 patients was calculated. The demographic and clinical characteristics associated with hepatic steatosis are described. ResultsThe prevalence of steatosis was 2.17% and 1.51% for NAFLD. The mean age was 62.42 years. The study included 114 (50.2%) women and 113 (49.8%) males. NAFLD was found in 147 (64.8%), and 64 (28.2%) were steatosis due to other causes. The proportion of patients with NAFLD and high transaminases was 24.13%, and the proportion of patients with NAFLD and GGT elevation was 18.6%. A high proportion of NAFLD had been found with cardiometabolic risk factors: 93.9% overweight and obesity, 55.1% diabetes, 54.4% hypertension, 32.9% metabolic syndrome, 35.2% hypertriglyceridaemia, and HDL risk 19.6%. A significant association was found between cardiometabolic risk factors and NAFLD in diabetes, obesity, and metabolic syndrome. DiscussionPrevalence was only 1.51%, perhaps because of the low importance given to this disease. There is a high proportion of NAFLD with cardiometabolic risk factors and more in the general population. If all the causes of steatosis are considered there is a significant association between obesity, diabetes mellitus, and metabolic syndrome with NAFLD. ConclusionsThe recorded prevalence of NAFLD is much lower than that of population studies, and a high presence of cardiometabolic factors has been found in these patients.

MicroRNA-26a-CD36 signaling pathway: Pivotal role in lipid accumulation in hepatocytes induced by PM2.5 liposoluble extracts

Exposure to ambient particular matters (PM) has been associated with the development of non-alcoholic fatty liver disease (NAFLD), but the underlying mechanism remains unclear. Given that microRNA (miRNA) is recognized as a key regulator of lipid metabolism and a potential mediator of environmental cues, this study aimed to explore the role of miRNA-mRNA regulation underlying abnormal lipid metabolism triggered by PM2.5liposoluble extracts. We confirmed that 72-h exposure to liposoluble extracts of PM2.5 from Nanjing at 25 μg/cm2 induced lipid accumulation in HepG2 cells by promoting uptake of free fatty acids (FFAs). Notably, lipid accumulation induced by PM2.5 liposoluble extracts was associated with decreased expression of miR-26a and consequent upregulation of fatty acid translocase (FAT, also known as CD36). Using gain- and loss-of-function assays, we demonstrated that miR-26a negatively regulated CD36 to mediate lipid accumulation in HepG2 cells. We further confirmed that miR-26a directly acted on the 3′ untranslated region (3′UTR) of CD36. Furthermore, overexpression of miR-26a abolished steatosis in HepG2 cells treated with PM2.5 liposoluble extracts by suppressing CD36. In addition, we demonstrated that PM2.5 liposoluble extracts caused inflammation in HepG2 cells by raising p65 phosphorylation, thereby fuelling the transition from simple non-alcoholic fatty liver to non-alcoholic steatohepatitis. In conclusion, this study demonstrated a novel mechanism by which miR-26a-CD36 pathway mediated lipid accumulation induced by PM2.5 liposoluble extracts in hepatocytes. Lipid accumulation and inflammation induced by PM2.5 liposoluble extracts implied the potential role of PM2.5 in developing NAFLD.

Stable Isotope-Labeled Lipidomics to Unravel the Heterogeneous Development Lipotoxicity.

Non-alcoholic fatty liver disease (NAFLD) as a global health problem has clinical manifestations ranging from simple non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), cirrhosis, and cancer. The role of different types of fatty acids in driving the early progression of NAFL to NASH is not understood. Lipid overload causing lipotoxicity and inflammation has been considered as an essential pathogenic factor. To correlate the lipid profiles with cellular lipotoxicity, we utilized palmitic acid (C16:0)- and especially unprecedented palmitoleic acid (C16:1)-induced lipid overload HepG2 cell models coupled with lipidomic technology involving labeling with stable isotopes. C16:0 induced inflammation and cell death, whereas C16:1 induced significant lipid droplet accumulation. Moreover, inhibition of de novo sphingolipid synthesis by myriocin (Myr) aggravated C16:0 induced lipoapoptosis. Lipid profiles are different in C16:0 and C16:1-treated cells. Stable isotope-labeled lipidomics elucidates the roles of specific fatty acids that affect lipid metabolism and cause lipotoxicity or lipid droplet formation. It indicates that not only saturation or monounsaturation of fatty acids plays a role in hepatic lipotoxicity but also Myr inhibition exasperates lipoapoptosis through ceramide in-direct pathway. Using the techniques presented in this study, we can potentially investigate the mechanism of lipid metabolism and the heterogeneous development of NAFLD.

Role of CD36 in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) includes nonalcoholic simple fatty liver, nonalcoholic steatohepatitis, liver cirrhosis, and liver cancer and is the most common liver disease in the world. The complex pathogenesis of NAFLD is a major concern among researchers. CD36 is a transmembrane glycoprotein that takes up fatty acid and binds to oxidized low-density lipoprotein in the liver, and therefore, it is involved in the development and progression of NAFLD. With reference to the latest research findings, this article reviews the association between CD36 and NAFLD and the role of CD36.