This new book entitled "Non-Alcoholic Fatty Liver Disease Research 2016" covers a selection of recent research topics and current review articles in the field of nonalcoholic fatty liver disease ...(NAFLD) that have been recently published in a monographic Special Issue of the International Journal of Molecular Sciences (IJMS) journal. <false,>NAFLD is an “umbrella” definition that encompasses a spectrum of histopathological liver changes ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) with/without fibrosis, “cryptogenic” cirrhosis and hepatocellular carcinoma. <false,>NAFLD has become one of the most common forms of chronic liver disease worldwide and its prevalence is expected to continue rising. <false,>It is now becoming increasingly clear that the clinical and economic burden of NAFLD does not only affect the liver, but also affects the risk of developing cardiovascular disease, type 2 diabetes mellitus, colo-rectal neoplasms, chronic kidney disease and other extra-hepatic diseases that have a considerable impact on health-care expenditures. <false,>Against this background, further research is needed to better understand the natural history, and the molecular pathogenesis of NAFLD, as well as to elucidate the underlying mechanisms by which NAFLD contributes to the increased cardiometabolic risk, and to disclose novel and effective treatment strategies for this increasingly prevalent and burdensome disease.<false,>Some of the leading international researchers in this area expressed a willingness to contribute to this book providing an updated, state-of-the-art view on the aforementioned topics, and also suggesting novel research avenues for NAFLD.
In recent years, the incidence rate of nonalcoholic fatty liver disease (NAFLD) has ascended with the increasing number of metabolic diseases such as obesity and diabetes, which will bring great ...medical burden to society. At present, multiple scientific experiments have found that the CCR4-NOT complex can participate in regulating obesity and energy metabolism. This study is designed to explore the role and mechanism of CCR4-NOT transcription complex subunit 7 (CNOT7), a subunit of the CCR4-NOT complex in liver lipid deposition.
To establish the NAFLD cell model, palmitic acid (PA) was utilized to stimulate HepG2 cells and LO2 cells, promoting intracellular lipid deposition. CNOT7 was knockdown by siRNA and lentivirus to evaluate the effect of CNOT7 in NAFLD.
Our results demonstrated that the expression of CNOT7 was increased in the NAFLD cell model. After knocking down CNOT7, the lipid deposition declined in HepG2 or LO2 cells treated by PA reduced. We found the lipid synthesis genes and the lipid uptake and transport factors in the CNOT7 knockdown group were significantly downregulated compared to the non-knockdown group. Furthermore, knockdown of CNOT7 might promote fatty acid oxidation.
Knocking down CNOT7 can improve lipid deposition and CNOT7 may be a potential therapeutic target for NAFLD.
•CNOT7 could become a target for improving liver lipid deposition.•After knocking down CNOT7, the lipid synthesis genes were significantly downregulated.•The knock down of CNOT7 also affected lipid uptake and transport factors and fatty acid oxidation genes.•CNOT7 could regular plenty of metabolic genes.
Non-alcoholic fatty liver disease (NAFLD) is now a public health issue worldwide, but no drug has yet received approval. Genistein, an isoflavonoid derived from soybean, ameliorates ...high-fat-diet-induced NAFLD in mice, but the molecular underpinnings remain largely elusive. Arachidonic acid (AA) is a major ingredient of animal fats, and the AA cascade has been implicated in chronic inflammation. In this study, we investigated whether genistein was against NAFLD by targeting the AA cascade. Using a mouse model, we showed that genistein supplementation improved high-fat-diet-induced NAFLD by normalizing hepatomegaly, liver steatosis, aminotransferase abnormalities, and glucose tolerance. The thromboxane A2 (TXA2) pathway was aberrantly active in NAFLD, evidenced by an elevation of circulating TXA2 and hepatic thromboxane A2 receptor expression. Mechanistically, we found that genistein directly targeted cyclooxygenase-1 activity as well as its downstream TXA2 biosynthesis, while the TXA2 pathway might mediate NAFLD progression by impairing insulin sensitivity. Taken together, our study revealed a crucial pathophysiological role of the TXA2 pathway in NAFLD and provided an explanation as to how genistein was against NAFLD progression.
Objective: Obesity affects 60% of adults in Europe. Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent obesity consequences that increase cardiovascular and hepatic morbidity and ...mortality. Here; it was aimed to compare NAFLD indexes with hepatic ultrasonography (USG) and determine whether these indexes could be used as predictors of hepatosteatosis in patients with obesity. Method: Eighty randomly chosen patients from our obesity center were included in the study. Patients ≥18 years-old, having files with all research parameters were included and having acute/chronic hepatic disease/malignancy, getting any kind of treatment for hepatosteatosis, having alcohol consumption above recommended amounts were excluded. All patients’ age, gender, weight, height, body mass index (BMI), waist circumference, gasting blood glucose, high-density lipoprotein, triglyceride, low-density lipoprotein, insulin, alanine transaminase (ALT), aspartate aminotransferase, gamma-glutamyl transferase, hepatic USG results, accompanying diseases and medicines were recorded. Nonalcoholic fatty liver disease indexes: Hepatosteatosis index (HSI), visceral adiposity index (VAI), fatty liver index (FLI) and lipid accumulation product index (LAP) were calculated. Results were evaluated using SPSS program. Results: Sixty-five female and 15 male, totally 80 people with obesity were included in the study. Mean age was 44.29±12.82 years in women and 38.27±12.88 years in men. In general population HS rates were: No hepatosteatosis 10%, first degree 17.05%, second degree: 58.75% and third degree: 13.75%. Weight, WC, ALT, diabetes mellitus, hypertension, being on medication for accompanying diseases and alcohol consumption within recommended rates were higher in HS(+) group when compared to HS(-) group. When HS levels were compared with mean NAFLD index values, there was statistically significant difference for HSI mean group values. There was no statistically significant difference for other NAFLD indexes. There was a positive correlation between BMI and LAP, FLI and HSI. There was no significant correlation between BMI and VAI. Conclusion: As NAFLD is a strong predictor of cardiometabolic morbidity and mortality, it is important to make a diagnosis before progression in people living with obesity and simple non-invasive screening/diagnostic tools are needed for this purpose. VAI, LAP, FLI, HSI are easily calculated scientific models that are found to be predicting NAFLD. Although we could only partially found this prediction, they could be used sufficiently after national validation studies that determine the cut-off values and help to achieve prevention of NAFLD-related complications with early diagnosis.
To assess the role of adipose tissue insulin resistance (Adipo-IR) in the pathogenesis of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and to determine Adipo-IR ...evolution during a lifestyle intervention program.
In this prospective, cohort study, children and adolescents with severe obesity were recruited between July 2020 and December 2022 at an inpatient pediatric rehabilitation center. Treatment consisted of dietary intervention and physical activity. Liver steatosis and fibrosis were evaluated using ultrasound and transient elastography with controlled attenuation parameter and liver stiffness measurement. Every 4 to 6 months, anthropometric measurements, serum biochemical analysis, ultrasound and elastography were repeated. Adipo-IR was estimated by the product of the fasting serum insulin times the fasting free fatty acid concentration and hepatic IR by the homeostatic model assessment for insulin resistance (HOMA-IR), respectively.
56% of 200 patients with obesity had evidence of steatosis on ultrasound and 26% were diagnosed with fibrosis (≥F2). Adipo-IR increased progressively from lean controls to patients with obesity to patients with MASLD and MASLD with fibrosis. Adipo-IR was already elevated in patients with only mild steatosis (p = 0.0403). Patients with more insulin-sensitive adipose tissue exhibited lower liver fat content (p < 0.05) and serum alanine transaminase levels (p = 0.001). Adipo-IR correlated positively with visceral adipose tissue weight, waist circumference, and the visceral adipose tissue/gynoid adipose tissue ratio (p < 0.001), but not with total body fat percentage (p = 0.263). After 4 to 6 months of lifestyle management, both MASLD and Adipo-IR improved.
Our data suggest that Adipo-IR is associated with the presence of pediatric MASLD, particularly steatosis.
The identification of biomarkers for the early diagnosis of nonalcoholic fatty liver disease (NAFLD) is urgently needed. Here, we aimed to identify NAFLD biomarkers in the early stages of steatosis ...(SS) and nonalcoholic steatohepatitis (NASH) based on differential gene expression from bioinformatics data.
A meta-analysis was performed from transcriptomic databases retrieved from public repositories containing data from biopsies of patients at various stages of NAFLD development. The status of the selected molecules was validated in the serum of patients with NAFLD by ELISA.
: We identified 121 differentially expressed genes (DEGs) associated with SS and 402 associated with NASH. Gene Ontology (GO) enrichment revealed that the altered genes were primarily associated with dysfunction of primary cellular processes, and pathway analyses were mainly related to cholesterol metabolism. We identified ACSS2, PCSK9, and CYP7A1 as candidate biomarkers for SS and ANGPTL3, CD36, CYP51A1, FASN, FAS, FDFT1, and LSS as candidate biomarkers for NASH.
By experimental validation of bioinformatics data from patients with NAFLD, we identified promising biomarkers for detecting SS and NASH that might be useful for screening and diagnosing early NAFLD stages in humans.
Background & Aims Some patients with nonalcoholic fatty liver disease (NAFLD) develop liver-related complications and have higher mortality than other patients with NAFLD. We determined the accuracy ...of simple, noninvasive scoring systems in identification of patients at increased risk for liver-related complications or death. Methods We performed a retrospective, international, multicenter cohort study of 320 patients diagnosed with NAFLD, based on liver biopsy analysis through 2002 and followed through 2011. Patients were assigned to mild-, intermediate-, or high-risk groups based on cutoff values for 2 of the following: NAFLD fibrosis score, aspartate aminotransferase/platelet ratio index, FIB-4 score, and BARD score. Outcomes included liver-related complications and death or liver transplantation. We used multivariate Cox proportional hazard regression analysis to adjust for relevant variables and calculate adjusted hazard ratios (aHRs). Results During a median follow-up period of 104.8 months (range, 3−317 months), 14% of patients developed liver-related events and 13% died or underwent liver transplantation. The aHRs for liver-related events in the intermediate-risk and high-risk groups, compared with the low-risk group, were 7.7 (95% confidence interval CI: 1.4−42.7) and 34.2 (95% CI: 6.5−180.1), respectively, based on NAFLD fibrosis score; 8.8 (95% CI: 1.1−67.3) and 20.9 (95% CI: 2.6−165.3) based on the aspartate aminotransferase/platelet ratio index; and 6.2 (95% CI: 1.4−27.2) and 6.6 (95% CI: 1.4−31.1) based on the BARD score. The aHRs for death or liver transplantation in the intermediate-risk and high-risk groups compared with the low-risk group were 4.2 (95% CI: 1.3−13.8) and 9.8 (95% CI: 2.7−35.3), respectively, based on the NAFLD fibrosis scores. Based on aspartate aminotransferase/platelet ratio index and FIB-4 score, only the high-risk group had a greater risk of death or liver transplantation (aHR = 3.1; 95% CI: 1.1−8.4 and aHR = 6.6; 95% CI: 2.3−20.4, respectively). Conclusions Simple noninvasive scoring systems help identify patients with NAFLD who are at increased risk for liver-related complications or death. NAFLD fibrosis score appears to be the best indicator of patients at risk, based on HRs. The results of this study require external validation.
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