scholarly journals The Potential Role of Cellular Senescence in Non-Alcoholic Fatty Liver Disease

2022 ◽  
Vol 23 (2) ◽  
pp. 652
Author(s):  
Cornelius Engelmann ◽  
Frank Tacke

Non-alcoholic fatty liver disease (NAFLD) represents an increasing global health burden. Cellular senescence develops in response to cellular injury, leading not only to cell cycle arrest but also to alterations of the cellular phenotype and metabolic functions. In this review, we critically discuss the currently existing evidence for the involvement of cellular senescence in NAFLD in order to identify areas requiring further exploration. Hepatocyte senescence can be a central pathomechanism as it may foster intracellular fat accumulation, fibrosis and inflammation, also due to secretion of senescence-associated inflammatory mediators. However, in some non-parenchymal liver cell types, such as hepatic stellate cells, senescence may be beneficial by reducing the extracellular matrix deposition and thereby reducing fibrosis. Deciphering the detailed interaction between NAFLD and cellular senescence will be essential to discover novel therapeutic targets halting disease progression.

2021 ◽  
Vol 93 (2) ◽  
pp. 169-173
Author(s):  
Ya. M. Vakhrushev ◽  
A. P. Lukashevich

Aim. To study the basic metabolic functions of the liver in patients with non-alcoholic fatty liver disease and to assess the relationship of these disorders with the bacterial overgrowth syndrome. Materials and methods. 50 patients with non-alcoholic fatty liver disease at the stage of steatosis were examined. In the verification of the diagnosis, hepatobiliary system ultrasound and FibroMax test data were used. A study was conducted of indicators of lipid, carbohydrate, protein, pigment, mineral metabolism and the exchange of enzymes in the blood. The bacterial overgrowth syndrome was studied by the results of a hydrogen breath test with lactulose using a LactofаH2 analyzer. Results. Patients with non-alcoholic fatty liver disease showed a significant increase in total cholesterol (median 5.9 mmol/l vs 5.0 mmol/l, p=0.000013), triglycerides (1.35 g/l vs 0.9 g/l, p=0.014), glucose (5.65 mmol/l against 5.1 mmol/l, p=0.000001) of blood serum compared with the control group. An increase in total protein and a tendency to decrease in albumin, an increase in serum sodium and calcium were detected. In patients with non-alcoholic fatty liver disease there is a significant increase in the markers of cytolysis and cholestasis compared with the control group. The bacterial overgrowth syndrome was detected in 72% of cases, with ileocecal valve function impaired in 50% of patients, gastrointestinal motility slowed down, or colon dysbiosis occurred. A correlation analysis revealed positive relationships between the bacterial overgrowth syndrome on the one hand and glucose (r=0.83, p0.05), total protein (r=0.35, p0.05), calcium (r=0.5, p0.05) on the other hand; negative relationship between the bacterial overgrowth syndrome and albumin (r=-0.8, p0.05). In this case, a positive relationship between the bacterial overgrowth syndrome and the increase in glycemia after glucose loading, that is, absorption in the small intestine, was revealed. Conclusion. The established violations of the metabolic functions of the liver with non-alcoholic fatty liver disease are closely related to the bacterial overgrowth syndrome.


2020 ◽  
Vol 9 (7) ◽  
pp. 2032 ◽  
Author(s):  
Lauren A. Newman ◽  
Michael J. Sorich ◽  
Andrew Rowland

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, affecting approximately one-third of the global population. Most affected individuals experience only simple steatosis—an accumulation of fat in the liver—but a proportion of these patients will progress to the more severe form of the disease, non-alcoholic steatohepatitis (NASH), which enhances the risk of cirrhosis and hepatocellular carcinoma. Diagnostic approaches to NAFLD are currently limited in accuracy and efficiency; and liver biopsy remains the only reliable way to confirm NASH. This technique, however, is highly invasive and poses risks to patients. Hence, there is an increasing demand for improved minimally invasive diagnostic tools for screening at-risk individuals and identifying patients with more severe disease as well as those likely to progress to such stages. Recently, extracellular vesicles (EVs)—small membrane-bound particles released by virtually all cell types into circulation—have emerged as a rich potential source of biomarkers that can reflect liver function and pathological processes in NAFLD. Of particular interest to the diagnosis and tracking of NAFLD is the potential to extract microRNAs miR-122 and miR-192 from EVs circulating in blood, particularly when using an isolation technique that selectively captures hepatocyte-derived EVs.


JHEP Reports ◽  
2021 ◽  
pp. 100301
Author(s):  
Abraham Stijn Meijnikman ◽  
Hilde Herrema ◽  
Torsten Scheithauer ◽  
Jeffrey Kroon ◽  
Max Nieuwdorp ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2072
Author(s):  
Tianhao Zhou ◽  
Debjyoti Kundu ◽  
Jonathan Robles-Linares ◽  
Vik Meadows ◽  
Keisaku Sato ◽  
...  

Fatty liver diseases, such as non-alcoholic fatty liver disease (NAFLD), are global health disparities, particularly in the United States, as a result of cultural eating habits and lifestyle. Pathological studies on NAFLD have been mostly focused on hepatocytes and other inflammatory cell types; however, the impact of other biliary epithelial cells (i.e., cholangiocytes) in the promotion of NAFLD is growing. This review article will discuss how cholestatic injury and cholangiocyte activity/ductular reaction influence NAFLD progression. Furthermore, this review will provide informative details regarding the fundamental properties of cholangiocytes and bile acid signaling that can influence NAFLD. Lastly, studies relating to the pathogenesis of NAFLD, cholangiopathies, and ductular reaction will be analyzed to help gain insight for potential therapies.


Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4946
Author(s):  
Ahran Song ◽  
Yoonjin Park ◽  
Boyong Kim ◽  
Seung Gwan Lee

Non-alcoholic fatty liver disease is caused by excessive lipid accumulation in hepatocytes. Although trans-anethole (TAO) affects hypoglycemia and has anti-immune activity and anti-obesity effects, its role in non-alcoholic fatty liver disease remains unknown. This study aimed to evaluate the effects of TAO on cellular senescence, lipid metabolism, and reinforcement of microenvironments in HepG2 cells. To analyze the lipid metabolic activity of TAO, PCR analysis, flow-cytometry, and Oil Red O staining were performed, and mitochondrial membrane potential (MMP) and cellular senescence kits were used for assessing the suppression of cellular senescence. At 2000 μg/mL TAO, the cellular viability was approximately 99%, and cell senescence decreased dose-dependently. In the results for MMP, activity increased with concentration. The levels of lipolytic genes, CPT2, ACADS, and HSL, strongly increased over 3 days and the levels of lipogenic genes, ACC1 and GPAT, were downregulated on the first day at 1000 μg/mL TAO. Consequently, it was found that TAO affects the suppression of cellular senescence, activation of lipid metabolism, and reinforcement of the microenvironment in HepG2 cells, and can be added as a useful component to functional foods to prevent fatty liver disease and cellular senescence, as well as increase the immunoactivity of the liver.


Author(s):  
Jeniffer Danielle M. Dutra ◽  
Quelson Coelho Lisboa ◽  
Silvia Marinho Ferolla ◽  
Carolina Martinelli M. L. Carvalho ◽  
Camila Costa M. Mendes ◽  
...  

Abstract. Some epidemiological evidence suggests an inverse correlation between non-alcoholic fatty liver disease (NAFLD) frequency and vitamin D levels. Likewise, a beneficial effect of vitamin D on diabetes mellitus (DM) and insulin resistance has been observed, but this is an unsolved issue. Thus, we aimed to investigate the prevalence of hypovitaminosis D in a NAFLD Brazilian population and its association with disease severity and presence of comorbidities. In a cross-sectional study, the clinical, biochemical and histological parameters of 139 NAFLD patients were evaluated according to two different cut-off points of serum 25-hydroxyvitamin D levels (20 ng/mL and 30 ng/mL). The mean age of the population was 56 ± 16 years, most patients were female (83%), 72% had hypertension, 88% dyslipidemia, 46% DM, 98% central obesity, and 82% metabolic syndrome. Serum vitamin D levels were < 30 ng/mL in 78% of the patients, and < 20 ng/mL in 35%. The mean vitamin D level was 24.3 ± 6.8 ng/mL. The comparison between the clinical, biochemical and histological characteristics of the patients according to the levels of vitamin D showed no significant difference. Most patients with NAFLD had hypovitaminosis D, but low vitamin D levels were not related to disease severity and the presence of comorbidities.


2008 ◽  
Vol 78 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Suano de Souza ◽  
Silverio Amancio ◽  
Saccardo Sarni ◽  
Sacchi Pitta ◽  
Fernandes ◽  
...  

Objectives: To evaluate the frequency of non-alcoholic fatty liver disease, the retinol serum levels, lipid profile, and insulin resistance in overweight/obese children. To relate these biochemical variables with the risk of this disease in the population studied. Methods: The study was cross-sectional and prospective, with 46 overweight/obese school children (28 female, 18 male; mean age 8.6 years). The control group consisted of 45 children, paired by age and gender. Hepatic steatosis, evaluated by ultrasound, was classified as normal, mild, moderate, or severe. Also evaluated were serum retinol levels; thiobarbituric acid reactive substances; lipid profile; and fasting glucose and serum insulin levels, used for the calculation of the Homeostasis Model Assessment. Results: Hepatic ultrasound alterations were found in 56.5% and 48,9% of the overweight/obese and control group children, respectively. Presence of obesity was associated with high levels of triglycerides (OR = 4.6; P = 0.002). In the studied children, the risk of steatosis was related to a trend to a higher percentage of retinol inadequacy (OR = 2.8; p = 0.051); there was no association with thiobarbituric acid reactive substances, lipid profile, or insulin resistance. Conclusions: The high frequency of non-alcoholic fatty liver disease in both groups, evaluated by hepatic ultrasound, in low-socioeconomic level children, independent of nutritional condition and without significant association with insulin resistance, emphasizes that especially in developing countries, other risk factors such as micronutrient deficiencies (e.g. vitamin A) are involved.


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