scholarly journals Expression of genes encoding mitochondrial proteins can distinguish nonalcoholic steatosis from steatohepatitis.

2007 ◽  
Vol 54 (2) ◽  
pp. 341-348 ◽  
Author(s):  
Piotr Bragoszewski ◽  
Andrzej Habior ◽  
Bozena Walewska-Zielecka ◽  
Jerzy Ostrowski
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Expression Profiles ◽  
Liver Steatosis ◽  
Mitochondrial Proteins ◽  
Morphological Examination ◽  
Nonalcoholic Fatty Liver ◽  
Triglyceride Accumulation ◽  
Genes Encoding

In patients without substantial alcohol use, triglyceride accumulation in the liver can lead to nonalcoholic fatty liver disease (NAFLD) that may progress to nonalcoholic steatohepatitis (NASH). The differential diagnosis between NAFLD and NASH can be accomplished only by morphological examination. Although the relationship between mitochondrial dysfunction and the progression of liver pathologic changes has been described, the exact mechanisms initiating primary liver steatosis and its progression to NASH are unknown. We selected 16 genes encoding mitochondrial proteins which expression was compared by quantitative RT-PCR in liver tissue samples taken from patients with NAFLD and NASH. We found that 6 of the 16 examined genes were differentially expressed in NAFLD versus NASH patients. The expression of hepatic HK1, UCP2, ME2, and ME3 appeared to be higher in NASH than in NAFLD patients, whereas HMGCS2 and hnRNPK expression was lower in NASH patients. Although the severity of liver morphological injury in the spectrum of NAFLD-NASH may be defined at the molecular level, expression of these selected 6 genes cannot be used as a molecular marker aiding histological examination. Moreover, it is still unclear whether these differences in hepatic gene expression profiles truly reflect the progression of morphological abnormalities or rather indicate various metabolic and hormonal states in patients with different degrees of fatty liver disease.

scholarly journals Sex Dimorphism of Nonalcoholic Fatty Liver Disease (NAFLD) in Pparg-Null Mice

2021 ◽  
Vol 22 (18) ◽  
pp. 9969
Author(s):  
Mariano Schiffrin ◽  
Carine Winkler ◽  
Laure Quignodon ◽  
Aurélien Naldi ◽  
Martin Trötzmüller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Liver Steatosis ◽  
Whole Body ◽  
Sex Dimorphism ◽  
Nonalcoholic Fatty Liver

Men with nonalcoholic fatty liver disease (NAFLD) are more exposed to nonalcoholic steatohepatitis (NASH) and liver fibrosis than women. However, the underlying molecular mechanisms of NALFD sex dimorphism are unclear. We combined gene expression, histological and lipidomic analyses to systematically compare male and female liver steatosis. We characterized hepatosteatosis in three independent mouse models of NAFLD, ob/ob and lipodystrophic fat-specific (PpargFΔ/Δ) and whole-body PPARγ-null (PpargΔ/Δ) mice. We identified a clear sex dimorphism occurring only in PpargΔ/Δ mice, with females showing macro- and microvesicular hepatosteatosis throughout their entire life, while males had fewer lipid droplets starting from 20 weeks. This sex dimorphism in hepatosteatosis was lost in gonadectomized PpargΔ/Δ mice. Lipidomics revealed hepatic accumulation of short and highly saturated TGs in females, while TGs were enriched in long and unsaturated hydrocarbon chains in males. Strikingly, sex-biased genes were particularly perturbed in both sexes, affecting lipid metabolism, drug metabolism, inflammatory and cellular stress response pathways. Most importantly, we found that the expression of key sex-biased genes was severely affected in all the NAFLD models we tested. Thus, hepatosteatosis strongly affects hepatic sex-biased gene expression. With NAFLD increasing in prevalence, this emphasizes the urgent need to specifically address the consequences of this deregulation in humans.

scholarly journals Nonalcoholic Fatty Liver Disease (NAFLD)—A New Cardiovascular Risk Factor in Peritoneal Dialysis Patients

2016 ◽  
Vol 36 (4) ◽  
pp. 427-432 ◽  
Author(s):  
Ivana Mikolasevic ◽  
Sandra Milic ◽  
Sanjin Racki ◽  
Luka Zaputovic ◽  
Davor Stimac ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Carotid Atherosclerosis ◽  
Liver Steatosis ◽  
Dialysis Patients ◽  
Cvd Risk ◽  
Nonalcoholic Fatty Liver

BackgroundRecent investigations indicated that nonalcoholic fatty liver disease (NAFLD), a hepatic component of metabolic syndrome (MS), is associated with an increased risk of cardiovascular disease (CVD). Accordingly, we were interested in exploring the frequency of NAFLD in peritoneal dialysis (PD) patients and analyzing factors in PD patients associated with NAFLD occurrence. In addition, we were interested in investigating whether NAFLD is associated with higher CVD risk in our PD patients.MethodsIn the present cross-sectional study, we analyzed 58 PD patients. The controlled attenuation parameter (CAP) was used to detect and quantify liver steatosis with the help of transient elastography (TE) (FibroScan, Echosense SA, Paris, France). A carotid ultrasound was performed in all patients to measure carotid intimae media thickness (IMT) and plaque as surrogate measures of increased CVD risk, and we investigated their association with NAFLD.ResultsNonalcoholic fatty liver disease was present in 74.1% of PD patients. Peritoneal dialysis/nonalcoholic fatty liver disease patients had statistically greater daily (136.5 ± 62.6 vs 93.6 ± 36.1; p = 0.02) and monthly (4,095.3 ± 1,877.7 vs 2,806.6 ± 1,083.2; p = 0.02) glucose load in comparison to the non-NAFLD/PD patients. In the next step, we were interested in analyzing what demographic and clinical characteristics in our PD patients are associated with a higher NAFLD occurrence. Presence of diabetes mellitus (DM), arterial hypertension (AH), dyslipidemia, body mass index > 25 kg/m2, and daily glucose load > 100 g were associated with NAFLD occurrence. Peritoneal dialysis patients with NAFLD showed more carotid atherosclerosis than PD patients without NAFLD. In addition, CAP values (as indicator of liver steatosis) showed strong positive association with IMT (r = 0.801; p < 0.0001). Nonalcoholic fatty liver disease was a strong predictor of carotid atherosclerosis in PD patients.ConclusionNonalcoholic fatty liver disease is highly prevalent in PD patients. Peritoneal dialysis patients with NAFLD are at high risk of atherosclerosis. Assessment of NAFLD in PD patients may be helpful for CVD risk stratification.

scholarly journals Nonalcoholic fatty liver disease without obesity: the problem to be solved

2017 ◽  
Vol 89 (12-2) ◽  
pp. 226-232
Author(s):  
A O Bueverov ◽  
P O Bogomolov
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Lifestyle Modification ◽  
Regulatory Element ◽  
Normal Weight ◽  
Atherogenic Dyslipidemia ◽  
Nonalcoholic Fatty Liver ◽  
Genes Encoding

It is generally agreed that nonalcoholic fatty liver disease (NAFLD) is a component of metabolic syndrome and is frequently associated with obesity, type 2 diabetes mellitus, atherogenic dyslipidemia, and other components of the syndrome. However, there is no doubt that not all overweight people develop NAFLD and, conversely, the latter may be present in normal weight individuals. The prevalence of NAFLD without obesity in different countries is very variable from 3 to 30%. Its risk factors are considered to be both exogenous (for example, excess intakes of cholesterol and rapidly assimilable fructose) and genetically determined (allelic variants of the genes encoding adiponutrin, the cholesteryl ester transport protein, sterol-regulatory element-binding protein 2). The methods for the diagnosis of NAFLD without obesity do not differ in essence from those for classic NAFLD. Analysis of the conducted investigations gives grounds to claim that lifestyle modification as exercises and dietary restrictions improves biochemical parameters and histological pattern. The efficiency of drug treatments needs further investigation.

scholarly journals Effects of Short- and Long-Term Soy Protein Feeding on Hepatic Cytochrome P450 Expression in Obese Nonalcoholic Fatty Liver Disease Rat Model

2021 ◽  
Vol 8 ◽  
Author(s):  
Melisa Kozaczek ◽  
Walter Bottje ◽  
Diyana Albataineh ◽  
Reza Hakkak
Keyword(s):  
Cytochrome P450 ◽  
Liver Disease ◽  
Fatty Liver ◽  
Rat Model ◽  
Soy Protein ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Short Term ◽  
Nonalcoholic Fatty Liver

Obesity can lead to chronic health complications such as nonalcoholic fatty liver disease (NAFLD). NAFLD is characterized by lipid aggregation in the hepatocytes and inflammation of the liver tissue as a consequence that can contribute to the development of cirrhosis and hepatocellular carcinoma (HCC). Previously, we reported that feeding obese Zucker rats with soy protein isolate (SPI) can reduce liver steatosis when compared with a casein (CAS) diet as a control. However, the effects of SPI on cytochrome P450 (CYP) in an obese rat model are less known. In addition, there is a lack of information concerning the consumption of soy protein in adolescents and its effect in reducing the early onset of NAFLD in this group. Our main goal was to understand if the SPI diet had any impact on the hepatic CYP gene expression when compared with the CAS diet. For this purpose, we used the transcriptomic data obtained in a previous study in which liver samples were collected from obese rats after short-term (eight-week) and long-term (16-week) feeding of SPI (n = 8 per group). To analyze this RNAseq data, we used Ingenuity Pathway Analysis (IPA) software. Comparing short- vs long-term feeding revealed an increase in the number of downregulated CYP genes from three at 8 weeks of SPI diet to five at 16 weeks of the same diet (P ≤ 0.05). On the other hand, upregulated CYP gene numbers showed a small increase in the long-term SPI diet compared to the short-term SPI diet, from 14 genes at 8 weeks to 17 genes at 16 weeks (P ≤ 0.05). The observed changes may have an important role in the attenuation of liver steatosis.

scholarly journals Hepatopulmonary syndrome: a rare manifestation of cirrhosis in patient with diencephalic obesity and nonalcoholic fatty liver disease after surgery for craniopharyngioma

2021 ◽  
Vol 67 (5) ◽  
pp. 58-66
Author(s):  
N. A. Mazerkina ◽  
A. N. Savateev ◽  
S. K. Gorelyshev ◽  
S. A. Mariashev ◽  
S. A. Beregovskaya ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Hepatopulmonary Syndrome ◽  
Surgical Excision ◽  
Nonalcoholic Fatty Liver ◽  
Triglyceride Accumulation ◽  
Rare Manifestation ◽  
End Stage

We describe a 15-year girl, who developed panhypopituitarism and diencephalic obesity after surgical excision of craniopharyngioma, followed by nonalcoholic fatty liver disease and cirrhosis 5 years after surgery. Cirrhosis in this case manifested by hypoxia due to hepatopulmonary syndrome, and despite cure of craniopharyngioma by surgery and radiosurgery treatment and adequate hormonal substitution therapy patient died 9 years after surgery. Growth hormone substitutional therapy in patients with hypopituitarism, and steatohepatitis may decrease liver triglyceride accumulation and prevent end-stage liver disease.

scholarly journals From Nonalcoholic Fatty Liver Disease (NAFLD) to Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) – New Terminology in Pediatric Patients as a Step in Good Scientific Direction?

2021 ◽  
Author(s):  
Marta Flisiak-Jackiewicz ◽  
Anna Bobrus-Chociej ◽  
Natalia Wasilewska ◽  
Dariusz Lebensztejn
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Visceral Obesity ◽  
Metabolic Dysfunction ◽  
Nonalcoholic Fatty Liver ◽  
Set Up ◽  
End Stage

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, which predispose to more serious hepatic conditions. It ranges from simple liver steatosis to nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis and even end-stage liver disease. Since obesity became one of the most important health concerns wordwide, a considerable increase in the prevalance of NAFLD and other metabolic implications has been observed, both in adults, and children. Due to the coexistence of visceral obesity, insulin resistance, dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome (MetS). These relationship between NAFLD and MetS led to set up in adults new term combining both of these conditions, called metabolic dysfunction-associated fatty liver disease (MAFLD). Based of these findings, we propose set of criteria, which may be useful to diagnose MAFLD in children and adolescents.

scholarly journals The Effects of Butyrate on Induced Metabolic-Associated Fatty Liver Disease in Precision-Cut Liver Slices

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4203
Author(s):  
Grietje H. Prins ◽  
Melany Rios-Morales ◽  
Albert Gerding ◽  
Dirk-Jan Reijngoud ◽  
Peter Olinga ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Type I Collagen ◽  
Smooth Muscle Actin ◽  
Liver Steatosis ◽  
Acid Oxidation ◽  
Type I ◽  
Triglyceride Accumulation ◽  
Liver Slices

Metabolic-associated fatty liver disease (MAFLD) starts with hepatic triglyceride accumulation (steatosis) and can progress to more severe stages such as non-alcoholic steatohepatitis (NASH) and even cirrhosis. Butyrate, and butyrate-producing bacteria, have been suggested to reduce liver steatosis directly and systemically by increasing liver β-oxidation. This study aimed to examine the influence of butyrate directly on the liver in an ex vivo induced MAFLD model. To maintain essential intercellular interactions, precision-cut liver slices (PCLSs) were used. These PCLSs were prepared from male C57BL/6J mice and cultured in varying concentrations of fructose, insulin, palmitic acid and oleic acid, to mimic metabolic syndrome. Dose-dependent triglyceride accumulation was measured after 24 and 48 h of incubation with the different medium compositions. PCLSs viability, as indicated by ATP content, was not affected by medium composition or the butyrate concentration used. Under induced steatotic conditions, butyrate did not prevent triglyceride accumulation. Moreover, it lowered the expression of genes encoding for fatty acid oxidation and only increased C4 related carnitines, which indicate butyrate oxidation. Nevertheless, butyrate lowered the fibrotic response of PCLSs, as shown by reduced gene expression of fibronectin, alpha-smooth muscle actin and osteopontin, and protein levels of type I collagen. These results suggest that in the liver, butyrate alone does not increase lipid β-oxidation directly but might aid in the prevention of MAFLD progression to NASH and cirrhosis.

scholarly journals Noninvasive Markers of Improvement of Liver Steatosis Achieved by Weight Reduction in Patients with Nonalcoholic Fatty Liver Disease

2015 ◽  
Vol 53 (1) ◽  
pp. 56-64 ◽  
Author(s):  
Ionel Copaci ◽  
Ioana Lupescu ◽  
Elena Caceaune ◽  
Grethi Chiriac ◽  
G. Ismail
Keyword(s):  
Physical Activity ◽  
Liver Disease ◽  
Waist Circumference ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Weight Reduction ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Moderate Intensity ◽  
Nonalcoholic Fatty Liver

Abstract Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance and metabolic syndrome, which are linked to obesity. The aim of the study was to assess if weight reduction through 12 months of lifestyle intervention and exercise would lead to improvement of steatosis. Methods. In a prospective observational study 86 overweight subjects (51 men, 35 women) with steatosis were recruited, after excluding other etiologies. Patients were assigned a caloric goal and a daily fat goal. Physical activity focused on moderate-intensity activities. Blood samples (biochemistry, HOMA-IR, cytokine levels, steatotest) were collected at entry and months 6 and 12. All subjects underwent abdominal CT scan before commencement and after 12 months to assess visceral and subcutaneous adipose tissue (VAT/SAT) area. Results. After 12 months baseline descriptive characteristics (weight, BMI, waist circumference) decreased significantly. Biochemical parameters that decreased significantly were: GGT (40.0 ± 18.0 vs 31.1 ± 13; p = 0.01), ALT (58.5 ± 23.5 vs 32,7 ± 14.8; p = 0.001), cholesterol (236.4 ± 54.8 vs 204.8 ± 91; p = 0.05), LDL (160.1 ± 47.4 vs 125.3 ± 40; p = 0.05) and HOMA-R (4.86 ± 0.63 vs 3 ± 0.41; p = 0.018). Steatotest improved significantly (0.68 ± 0.16 vs 0.38 ± 0.14; p = 0.02). Modification of adipocytokines was significant for leptin (p = 0.018) and adiponectin (p = 0.003). Factors associated with regression of steatosis were weight, BMI, ALT, waist circumference, GGT, HOMA, leptin, VAT and steatotest. Multivariate logistic regression showed the following factors related to improved steatosis: BMI < 25 kg/m2, ALT < 42 U/L, leptin < 10.5 ng/ml and adiponectin > 8.4 μg/ml. Conclusions. Overweight persons who achieve significant reductions in body weight through 12 months of physical activity and low caloric diet can decrease liver fat, VAT and SAT. Even in those with minimal weight loss ALT levels, steatosis, adipokines and cardiovascular risk factors improved.

scholarly journals Diagnostic Accuracy of Platelet Count and Platelet Indices in Noninvasive Assessment of Fibrosis in Nonalcoholic Fatty Liver Disease Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Tamara Milovanovic Alempijevic ◽  
Milica Stojkovic Lalosevic ◽  
Igor Dumic ◽  
Nevena Jocic ◽  
Aleksandra Pavlovic Markovic ◽  
...  
Keyword(s):  
Platelet Count ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Distribution Width ◽  
Nonalcoholic Fatty Liver ◽  
Significant Difference

Objective. Keeping in mind the rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the need to establish noninvasive tests for its detection, the aim of our study was to investigate whether platelet count (PC), mean platelet volume (MPV), and platelet distribution width (PDW) can predict the presence of liver fibrosis in this group of patients. Methods. In 98 patients with NAFLD and 60 healthy volunteers, complete blood counts with automated differential counts were performed and values of PC, PDW, MPV, and PCT were analyzed. Results. Patients with NAFLD had lower PC and higher MPV, PCT, and PDW compared to the controls (P < 0.05). When NAFLD group was stratified according to severity of liver fibrosis, there was a statistically significant difference in the average values of PDW and PC between the groups (P < 0.05). Conclusion. Patients with NAFLD have significantly higher values of PCT, PDW, and MPV when compared to the healthy controls. Further studies are needed to establish their potential use for prediction of the degree of liver steatosis and fibrosis in NAFLD patients.

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