scholarly journals Relationship between IL-8 Circulating Levels and TLR2 Hepatic Expression in Women with Morbid Obesity and Nonalcoholic Steatohepatitis

2020 ◽  
Vol 21 (11) ◽  
pp. 4189 ◽  
Author(s):  
Teresa Auguet ◽  
Laia Bertran ◽  
Jessica Binetti ◽  
Carmen Aguilar ◽  
Salomé Martínez ◽  
...  
Keyword(s):  
Morbid Obesity ◽  
Nonalcoholic Steatohepatitis ◽  
Normal Liver ◽  
Normal Weight ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Expression ◽  
Tnf Α ◽  
Noninvasive Biomarkers ◽  
The Relationship ◽  
Circulating Levels

The progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) is linked to systemic inflammation. Currently, two of the aspects that need further investigation are diagnosis and treatment of NASH. In this sense, the aim of this study was to assess the relationship between circulating levels of cytokines, hepatic expression of toll-like receptors (TLRs), and degrees of NAFLD, and to investigate whether these levels could serve as noninvasive biomarkers of NASH. The present study assessed plasma levels of cytokines in 29 normal-weight women and 82 women with morbid obesity (MO) (subclassified: normal liver (n = 29), simple steatosis (n = 32), and NASH (n = 21)). We used enzyme-linked immunosorbent assays (ELISAs) to quantify cytokine and TLR4 levels and RTqPCR to assess TLRs hepatic expression. IL-1β, IL-8, IL-10, TNF-α, tPAI-1, and MCP-1 levels were increased, and adiponectin levels were decreased in women with MO. IL-8 was significantly higher in MO with NASH than in NL. To sum up, high levels of IL-8 were associated with the diagnosis of NASH in a cohort of women with morbid obesity. Moreover, a positive correlation between TLR2 hepatic expression and IL-8 circulating levels was found.

scholarly journals Circulating Levels of Pro-Neurotensin and Its Relationship with Nonalcoholic Steatohepatitis and Hepatic Lipid Metabolism

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 373
Author(s):  
Beatriz Villar ◽  
Laia Bertran ◽  
Carmen Aguilar ◽  
Jessica Binetti ◽  
Salomé Martínez ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Nonalcoholic Steatohepatitis ◽  
Liver Lipid ◽  
Normal Liver ◽  
Normal Weight ◽  
Published Data ◽  
Mrna Levels ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Expression ◽  
Liver Lipid Metabolism

Recent studies suggest a link between pro-neurotensin (pro-NT) and nonalcoholic fatty liver disease (NAFLD), but the published data are conflicting. Thus, we aimed to analyze pro-NT levels in women with morbid obesity (MO) and NAFLD to investigate if this molecule is involved in NAFLD and liver lipid metabolism. Plasma levels of pro-NT were determined in 56 subjects with MO and 18 with normal weight (NW). All patients with MO were subclassified according to their liver histology into the normal liver (NL, n = 20) and NAFLD (n = 36) groups. The NAFLD group had 17 subjects with simple steatosis (SS) and 19 with nonalcoholic steatohepatitis (NASH). We used a chemiluminescence sandwich immunoassay to quantify pro-NT in plasma and RT-qPCR to evaluate the hepatic mRNA levels of several lipid metabolism-related genes. We reported that pro-NT levels were significantly higher in MO with NAFLD than in MO without NAFLD. Additionally, pro-NT levels were higher in NASH patients than in NL. The hepatic expression of lipid metabolism-related genes was found to be altered in NAFLD, as previously reported. Additionally, although pro-NT levels correlated with LDL, there was no association with the main lipid metabolism-related genes. These findings suggest that pro-NT could be related to NAFLD progression.

scholarly journals Deregulated Serotonin Pathway in Women with Morbid Obesity and NAFLD

Life ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 245
Author(s):  
Jessica Binetti ◽  
Laia Bertran ◽  
David Riesco ◽  
Carmen Aguilar ◽  
Salomé Martínez ◽  
...  
Keyword(s):  
Morbid Obesity ◽  
Normal Liver ◽  
Protective Role ◽  
Normal Weight ◽  
Pcr Analysis ◽  
Alcoholic Fatty Liver ◽  
Hepatic Expression ◽  
Important Regulator ◽  
The Relationship ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) extends from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH). Peripheral serotonin (5-HT) has become as an important regulator of different metabolic pathways. 5-HT has been related to obesity and lipid accumulation in the liver. The objective of this study was to assess the relationship between the 5-HT signaling pathway and the degree of NAFLD, as well as to investigate whether peripheral 5-HT levels are related to the hepatic and jejunal mRNA abundance of serotonin receptors (HTR) in a cohort of women with morbid obesity (MO) and NAFLD. ELISA was used to quantify the serum 5-HT from normal-weight subjects (n = 26) and patients with MO (n = 58). We used RTq-PCR analysis to evaluate the relative expression of HTR in women with MO with normal liver (n = 22), SS (n = 21), and NASH (n = 15). The 5-HT was diminished in women with MO under a hypocaloric diet, regardless of the presence of NAFLD. Additionally, we report a negative correlation of 5-HT levels with metabolic syndrome criteria, suggesting that serotonin may have a protective role in obesity. Additionally, the hepatic expression of HTR2A and HTR2B were decreased in women with MO and NAFLD, but no significant differences in the HTR jejunal expression according to the presence of NAFLD were found.

scholarly journals The Potential Protective Role of RUNX1 in Nonalcoholic Fatty Liver Disease

2021 ◽  
Vol 22 (10) ◽  
pp. 5239
Author(s):  
Laia Bertran ◽  
Angela Pastor ◽  
Marta Portillo-Carrasquer ◽  
Jessica Binetti ◽  
Carmen Aguilar ◽  
...  
Keyword(s):  
Morbid Obesity ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Normal Liver ◽  
Protective Role ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Expression

The pathogenic mechanisms underlying nonalcoholic fatty liver disease (NAFLD) are beginning to be understood. RUNX1 is involved in angiogenesis, which is crucial in inflammation, but its role in nonalcoholic steatohepatitis (NASH) remains unclear. The aim of this study was to analyze RUNX1 mRNA hepatic and jejunal abundance in women with morbid obesity (MO) and NAFLD. RUNX1, lipid metabolism-related genes, and TLRs in women with MO and normal liver (NL, n = 28), NAFLD (n = 41) (simple steatosis (SS, n = 24), or NASH (n = 17)) were analyzed by RT-qPCR. The RUNX1 hepatic expression was higher in SS than in NL or NASH, as likewise confirmed by immunohistochemistry. An increased expression of hepatic FAS was found in NAFLD. Hepatic RUNX1 correlated positively with FAS. There were no significant differences in the jejunum RUNX1 expressions in the different groups. Jejunal FXR expression was lower in NASH than in NL, while the TLR9 expression increased as NAFLD progressed. Jejunal RUNX1 correlated positively with jejunal PPARγ, TLR4, and TLR5. In summary, the hepatic expression of RUNX1 seems to be involved in the first steps of the NAFLD process; however, in NASH, it seems to be downregulated. Our findings provide important insights into the role of RUNX1 in the context of NAFLD/NASH, suggesting a protective role.

The association between a metabolically healthy overweight/obesity phenotype and markers of inflammation among Chinese children and adolescents aged 10–18 years

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jinyu Zhou ◽  
Ling Bai ◽  
Yangyang Dong ◽  
Rongrong Cai ◽  
Wenqing Ding
Keyword(s):  
Children And Adolescents ◽  
Inflammatory Markers ◽  
Normal Weight ◽  
Chinese Children ◽  
Metabolic Phenotypes ◽  
Tnf Α ◽  
Metabolically Healthy ◽  
Hs Crp ◽  
The Relationship ◽  
Chinese Children And Adolescents

Abstract Objectives The association between metabolically healthy overweight/obesity (MHO) and inflammatory markers remains controversial. The aim of the present study was to describe the prevalence of different metabolic phenotypes and to examine the relationship of different metabolic phenotypes with inflammatory markers among Chinese children and adolescents. Methods The study included 1,125 children and adolescents aged 10–18 years using a cross-sectional survey, and all subjects were classified into four groups based on a combination of BMI and metabolic status. In addition, the inflammatory markers we measured were high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Results The prevalence of metabolically healthy with normal-weight (MHNW), MHO, metabolically unhealthy with normal-weight (MUNW), and metabolically unhealthy overweight/obesity (MUO) phenotypes was 38.76, 7.11, 38.67 and 15.47%, respectively. The results of logistic regression analysis showed that the MHO was associated with the z scores of hs-CRP in Chinese children and adolescents (OR=0.57, 95% CI: 0.39–0.83). Meanwhile, multivariate adjusted regression analysis showed that the relationship between hs-CRP and MHO among the overweight/obese was consistent with the results above, but among the normal-weight, only the highest quartile of TNF-α could increase the risk of MUNW (OR=1.65, 95% CI: 1.09–2.52). Conclusions MHO phenotypes were not common in Chinese children and adolescents. Individuals with MHO had a more beneficial hs-CRP profile than those with MUO.

scholarly journals Effects of Caffeine and Chlorogenic Acid on Nonalcoholic Steatohepatitis in Mice Induced by Choline-Deficient, L-Amino Acid-Defined, High-Fat Diet

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3886
Author(s):  
Erdenetsogt Dungubat ◽  
Shiori Watabe ◽  
Arisa Togashi-Kumagai ◽  
Masato Watanabe ◽  
Yasuyuki Kobayashi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Chlorogenic Acid ◽  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
Cell Injury ◽  
Control Diet ◽  
Experimental Studies ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Expression

Several recent experimental studies have investigated the effects of caffeine and chlorogenic acid (CGA), representative ingredients of coffee, on nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). However, the results are conflicting, and their effects are yet to be clarified. In the present study, we examined the effects of caffeine and CGA on choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-fed mice, relatively new model mice of NASH. Seven-week-old male C57BL/6J mice were divided into the following groups: Control diet (control), CDAHFD (CDAHFD), CDAHFD supplemented with 0.05% (w/w) caffeine (caffeine), and CDAHFD supplemented with 0.1% (w/w) CGA (CGA). After seven weeks, the mice were killed and serum biochemical, histopathological, and molecular analyses were performed. Serum alanine aminotransferase (ALT) levels were significantly higher in the caffeine and CGA groups than in the CDAHFD group. On image analysis, the prevalence of Oil red O-positive areas (reflecting steatosis) was significantly higher in the caffeine group than in the CDAHFD group, and that of CD45R-positive areas (reflecting lymphocytic infiltration) in the hepatic lobule was significantly higher in the caffeine and CGA groups than in the CDAHFD group. Hepatic expression of interleukin (IL)-6 mRNA was higher in the caffeine and CGA groups than in the CDAHFD group, and the difference was statistically significant for the caffeine group. In conclusion, in the present study, caffeine and CGA significantly worsened the markers of liver cell injury, inflammation, and/or steatosis in NASH lesions in mice.

scholarly journals Hepatic transcriptome signatures in patients with varying degrees of nonalcoholic fatty liver disease compared with healthy normal-weight individuals

2019 ◽  
Vol 316 (4) ◽  
pp. G462-G472 ◽  
Author(s):  
Malte P. Suppli ◽  
Kristoffer T. G. Rigbolt ◽  
Sanne S. Veidal ◽  
Sara Heebøll ◽  
Peter Lykke Eriksen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Fatty Liver Disease ◽  
Normal Weight ◽  
Histological Techniques ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Hepatic Transcriptome

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of conditions ranging from simple steatosis (NAFL), over nonalcoholic steatohepatitis (NASH) with or without fibrosis, to cirrhosis with end-stage disease. The hepatic molecular events underlying the development of NAFLD and transition to NASH are poorly understood. The present study aimed to determine hepatic transcriptome dynamics in patients with NAFL or NASH compared with healthy normal-weight and obese individuals. RNA sequencing and quantitative histomorphometry of liver fat, inflammation and fibrosis were performed on liver biopsies obtained from healthy normal-weight ( n = 14) and obese ( n = 12) individuals, NAFL ( n = 15) and NASH ( n = 16) patients. Normal-weight and obese subjects showed normal liver histology and comparable gene expression profiles. Liver transcriptome signatures were largely overlapping in NAFL and NASH patients, however, clearly separated from healthy normal-weight and obese controls. Most marked pathway perturbations identified in both NAFL and NASH were associated with markers of lipid metabolism, immunomodulation, extracellular matrix remodeling, and cell cycle control. Interestingly, NASH patients with positive Sonic hedgehog hepatocyte staining showed distinct transcriptome and histomorphometric changes compared with NAFL. In conclusion, application of immunohistochemical markers of hepatocyte injury may serve as a more objective tool for distinguishing NASH from NAFL, facilitating improved resolution of hepatic molecular changes associated with progression of NAFLD. NEW & NOTEWORTHY Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. NAFLD is associated with the metabolic syndrome and can progress to the more serious form, nonalcoholic steatohepatitis (NASH), and ultimately lead to irreversible liver damage. Using gold standard molecular and histological techniques, this study demonstrates that the currently used diagnostic tools are problematic for differentiating mild NAFLD from NASH and emphasizes the marked need for developing improved histological markers of NAFLD progression.

scholarly journals Cardiac Morphology, Function, and Hemodynamics in Patients With Morbid Obesity and Nonalcoholic Steatohepatitis

2021 ◽  
Vol 10 (8) ◽  
Author(s):  
Grzegorz Styczynski ◽  
Piotr Kalinowski ◽  
Łukasz Michałowski ◽  
Rafał Paluszkiewicz ◽  
Bogna Ziarkiewicz‐Wróblewska ◽  
...  
Keyword(s):  
Morbid Obesity ◽  
Liver Biopsy ◽  
Right Ventricular ◽  
Nonalcoholic Steatohepatitis ◽  
Left Ventricular ◽  
Interquartile Range ◽  
Additional Risk Factor ◽  
Nonalcoholic Fatty Liver ◽  
Cardiac Morphology ◽  
Hyperdynamic Circulation

Background The patients with nonalcoholic fatty liver disease demonstrate an increased cardiovascular risk. The adverse influence of liver abnormalities on cardiac function are among many postulated mechanisms behind this association. The aim of the study was to evaluate cardiac morphology and function in patients with morbid obesity referred for bariatric surgery with liver biopsy. Methods and Results We evaluated with echocardiography 171 consecutive patients without known cardiac disease (median age 42 [interquartile range, 37–48] years, median body mass index 43.7 [interquartile range, 41.0–47.5], 67% female patients. Based on the liver biopsy results, there were 44 patients with nonalcoholic steatohepatitis (NASH), 69 patients with isolated steatosis, and 58 patients without steatosis. Patients with NASH demonstrated signs of left ventricular concentric remodeling and hyperdynamic circulation, including indexed left ventricular end‐diastolic diameter [cm/m 2 ]: NASH 1.87 [0.22]; isolated steatosis 2.03 [0.33]; without steatosis 2.01 [0.19], P =0.001; relative wall thickness: NASH 0.49±0.05, isolated steatosis 0.47±0.06, without steatosis 0.46±0.06, P =0.011; cardiac index [L/m 2 ]: NASH 3.05±0.54, isolated steatosis 2.80±0.44, without steatosis 2.79±0.50, P =0.013. After adjustment for sex, age, blood pressure, and heart rate, most of the measures of the left ventricular systolic and diastolic function, left atrial size, right ventricular function, and right ventricular size did not differ between groups. Conclusions In a group of patients with extreme obesity, NASH was associated with left ventricular concentric remodeling and hyperdynamic circulation. Increased cardiac output in NASH may represent an additional risk factor for incident cardiovascular events in this population.

scholarly journals Expression of Jejunal Taste Receptors in Women with Morbid Obesity

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2437
Author(s):  
Laia Bertran ◽  
Marta Portillo-Carrasquer ◽  
Salomé Martínez ◽  
Carmen Aguilar ◽  
Miguel Lopez-Dupla ◽  
...  
Keyword(s):  
Morbid Obesity ◽  
Metabolic Disorders ◽  
Normal Liver ◽  
Nutrient Sensing ◽  
Peroxisome Proliferator ◽  
Taste Receptors ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Glucose Levels ◽  
Hepatic Histology

Nutrient sensing plays important roles in promoting satiety and maintaining good homeostatic control. Taste receptors (TAS) are located through the gastrointestinal tract, and recent studies have shown they have a relationship with metabolic disorders. The aim of this study was to analyze the jejunal expression of TAS1R2, TAS1R3, TAS2R14 and TAS2R38 in women with morbid obesity, first classified according to metabolic syndrome presence (MetS; n = 24) or absence (non-MetS; n = 45) and then classified according to hepatic histology as normal liver (n = 28) or nonalcoholic fatty liver disease (n = 41). Regarding MetS, we found decreased expression of TAS2R14 in MetS patients. However, when we subclassified patients according to liver histology, we did not find differences between groups. We found negative correlations between glucose levels, triglycerides and MetS with TAS1R3 expression. Moreover, TAS2R14 jejunal expression correlated negatively with the presence of MetS and ghrelin levels and positively with the jejunal Toll-like receptor (TLR)4, peroxisome proliferator-activated receptor (PPAR)-γ, and interleukin (IL)-10 levels. Furthermore, TAS2R38 expression correlated negatively with TLR9 jejunal expression and IL-6 levels and positively with TLR4 levels. Our findings suggest that metabolic dysfunctions such as MetS trigger downregulation of the intestinal TASs. Therefore, taste receptors modulation could be a possible therapeutic target for metabolic disorders.

scholarly journals Equol Production Status is An Effective Predictor of Nonalcoholic Steatohepatitis in Women

2021 ◽  
Author(s):  
Takemi Akahane ◽  
Daisuke Kaya ◽  
Ryuichi Noguchi ◽  
Kosuke Kaji ◽  
Haruna Miyakawa ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Intestinal Microflora ◽  
Fasting Glucose ◽  
Antioxidant Activities ◽  
Nonalcoholic Fatty Liver ◽  
Histological Features ◽  
Menopausal Women ◽  
The Status ◽  
The Relationship ◽  
Nafld Activity Score

Abstract Equol is a metabolite of daidzein, a major soybean isoflavone with estrogenic and antioxidant activities. As the production of equol depends on the presence of certain members of the intestinal microflora, not all individuals can produce equol. The incidence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) increases in menopausal women, and estrogen is associated with the progression of NAFLD/NASH. Therefore, the status of equol production might also be related to the pathogenesis of NAFLD/NASH in women. We, thus, examined the relationship between NASH histological features and equol production. Thirty-eight NAFLD patients who underwent liver biopsy were included in this study. In women, the degree of fibrosis and ballooning in nonproducers was significantly higher than that in producers. The percentage of nonproducers with NAFLD activity score (NAS) ≥5 was significantly higher than that of producers. None of the histological features were significantly different between nonproducers and producers in men. Decision tree analysis identified the predictors of NAS ≥5 in women. The status of equol production was the strongest predictor, followed by fasting glucose. Equol can be noninvasively detected in urine, suggesting its application as a screening test for predicting the diagnosis and progression of NASH in women.

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