TNF-α is not the cause of fatty liver disease in obese diabetic mice

Background and AimCirculating levels of interleukin (IL)-6, a well-known inflammatory cytokine, are often elevated in coronavirus disease-2019 (COVID-19). Elevated IL-6 levels are also observed in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Our study aimed to describe the association between circulating IL-6 levels and MAFLD at hospital admission with risk of severe COVID-19.MethodsA total of 167 patients with laboratory-confirmed COVID-19 from three Chinese hospitals were enrolled. Circulating levels of IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured at admission. All patients were screened for fatty liver by computed tomography. Forty-six patients were diagnosed as MAFLD.ResultsPatients with MAFLD (n = 46) had higher serum IL-6 levels (median 7.1 [interquartile range, 4.3–20.0] vs. 4.8 [2.6–11.6] pg/mL, p = 0.030) compared to their counterparts without MAFLD (n = 121). After adjustment for age and sex, patients with MAFLD had a ~2.6-fold higher risk of having severe COVID-19 than those without MAFLD. After adjustment for age, sex and metabolic co-morbidities, increased serum IL-6 levels remained associated with higher risk of severe COVID-19, especially among infected patients with MAFLD (adjusted-odds ratio 1.14, 95% CI 1.05–1.23; p = 0.002). There was a significant interaction effect between serum IL-6 levels and MAFLD for risk of severe COVID-19 (p for interaction = 0.008).ConclusionsPatients with MAFLD and elevated serum IL-6 levels at admission are at higher risk for severe illness from COVID-19.

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Effect of dietary intervention, with or without co-interventions, on inflammatory markers in patients with nonalcoholic fatty liver disease: a systematic literature review

Nutrition Reviews ◽

10.1093/nutrit/nuz029 ◽

2019 ◽

Vol 77 (11) ◽

pp. 765-786 ◽

Cited By ~ 2

Author(s):

Anjana J Reddy ◽

Elena S George ◽

Stuart K Roberts ◽

Audrey C Tierney

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Inflammatory Markers ◽

Fatty Liver Disease ◽

Dietary Intervention ◽

Cochrane Library ◽

Dietary Interventions ◽

Nonalcoholic Fatty Liver ◽

Tnf Α

Abstract Context Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver disorders, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), with inflammation acting as a key driver in its pathogenesis and progression. Diet has the potential to mediate the release of inflammatory markers; however, little is known about the effects of various diets. Objective This systematic review aimed to evaluate the effect of dietary interventions on cytokines and adipokines in patients with NAFLD. Data Sources The electronic databases MEDLINE, EMBASE, CINAHL, and Cochrane Library were searched for clinical trials investigating dietary interventions, with or without supplementation, on cytokines and adipokines in NAFLD patients. Data Extraction Basic characteristics of populations, dietary intervention protocol, cytokines, and adipokines were extracted for each study. Quality of evidence was assessed using the American Dietetic Association criteria. Data Analysis Nineteen studies with a total of 874 participants were included. The most frequently reported inflammatory outcomes were C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), adiponectin, and leptin. Hypocaloric, isocaloric, or low-fat diets significantly (P < 0.05) lowered levels of CRP, TNF-α, and adiponectin. The addition of nutraceutical or pharmacological supplementation to dietary interventions appeared to elicit additional benefits for all of the most frequently reported inflammatory markers. Conclusions Hypo- or isocaloric diets alone, or with co-interventions that included a nutraceutical or pharmacological supplementation, appear to improve the inflammatory profile in patients with NAFLD. Thus, anti-inflammatory diets may have the potential to improve underlying chronic inflammation that underpins the pathophysiological mechanisms of NAFLD. In the absence of any known liver-sensitive markers, the use of cytokines and adipokines as a surrogate marker of liver disease should be further investigated in well-controlled trials.

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LPS-induced TNF-α factor mediates pro-inflammatory and pro-fibrogenic pattern in non-alcoholic fatty liver disease

Oncotarget ◽

10.18632/oncotarget.5163 ◽

2015 ◽

Vol 6 (39) ◽

pp. 41434-41452 ◽

Cited By ~ 55

Author(s):

Sara Ceccarelli ◽

Nadia Panera ◽

Marco Mina ◽

Daniela Gnani ◽

Cristiano De Stefanis ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Tnf Α ◽

Alcoholic Fatty Liver Disease

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Raw Bowl Tea (Tuocha) Polyphenol Prevention of Nonalcoholic Fatty Liver Disease by Regulating Intestinal Function in Mice

Biomolecules ◽

10.3390/biom9090435 ◽

2019 ◽

Vol 9 (9) ◽

pp. 435 ◽

Cited By ~ 11

Author(s):

Bihui Liu ◽

Jing Zhang ◽

Peng Sun ◽

Ruokun Yi ◽

Xiaoyan Han ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Density Lipoprotein ◽

The Body ◽

Lipoprotein Cholesterol ◽

Intestinal Function ◽

Alcoholic Fatty Liver ◽

Body Tissues ◽

Tnf Α

A high-fat diet-induced C57BL/6N mouse model of non-alcoholic fatty liver disease (NAFLD) was established. The effect and mechanism of Raw Bowl Tea polyphenols (RBTP) on preventing NAFLD via regulating intestinal function were observed. The serum, liver, epididymis, small intestine tissues, and feces of mice were examined by biochemical and molecular biological methods, and the composition of RBTP was analyzed by HPLC assay. The results showed that RBTP could effectively reduce the body weight, liver weight, and liver index of NAFLD mice. The serum effects of RBTP were: (1) decreases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), D-lactate (D-LA), diamine oxidase (DAO), lipopolysaccharide (LPS), and an increase of high density lipoprotein cholesterol (HDL-C) levels; (2) a decrease of inflammatory cytokines such as interleukin 1 beta (IL-1β), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α), and interferon gamma (INF-γ); (3) a decrease the reactive oxygen species (ROS) level in liver tissue; and (4) alleviation of pathological injuries of liver, epididymis, and small intestinal tissues caused by NAFLD and protection of body tissues. qPCR and Western blot results showed that RBTP could up-regulate the mRNA and protein expressions of LPL, PPAR-α, CYP7A1, and CPT1, and down-regulate PPAR-γ and C/EBP-α in the liver of NAFLD mice. In addition, RBTP up-regulated the expression of occludin and ZO-1, and down-regulated the expression of CD36 and TNF-α in the small intestines of NAFLD mice. Studies on mice feces showed that RBTP reduced the level of Firmicutes and increased the minimum levels of Bacteroides and Akkermansia, as well as reduced the proportion of Firmicutes/Bacteroides in the feces of NAFLD mice, which play a role in regulating intestinal microecology. Component analysis showed that RBTP contained seven polyphenolic compounds: Gallic acid, (-)-epigallocatechin, catechin, L-epicatechin, (-)-epigallocatechin gallate, (-)-gallocatechin gallate, and (-)-epicatechin gallate (ECG), and high levels of caffeine, (-)-epigallocatechin (EGC), and ECG. RBTP improved the intestinal environment of NAFLD mice with the contained active ingredients, thus playing a role in preventing NAFLD. The effect was positively correlated with the dose of 100 mg/kg, which was even better than that of the clinical drug bezafibrate.

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Rhein lysinate decreases inflammation and adipose infiltration in KK/HlJ diabetic mice with non-alcoholic fatty liver disease

Archives of Pharmacal Research ◽

10.1007/s12272-016-0770-4 ◽

2016 ◽

Vol 39 (7) ◽

pp. 960-969 ◽

Cited By ~ 7

Author(s):

Jie Wei ◽

Yong-Zhan Zhen ◽

Ju Cui ◽

Fa-Lin He ◽

Tao Shen ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Diabetic Mice ◽

Alcoholic Fatty Liver ◽

Rhein Lysinate ◽

Alcoholic Fatty Liver Disease

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P95 Effects of GH and IGF-1 treatments on body composition, glucose metabolism and hepatic gene expression in obese/diabetic mice with nonalcoholic fatty liver disease

Growth Hormone & IGF Research ◽

10.1016/s1096-6374(10)70195-7 ◽

2010 ◽

Vol 20 ◽

pp. S74-S75

Author(s):

E.O. List ◽

J.D. Blischak ◽

D.E. Berryman ◽

E. Lubbers ◽

R. Malgor ◽

...

Keyword(s):

Gene Expression ◽

Body Composition ◽

Liver Disease ◽

Glucose Metabolism ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Hepatic Gene Expression ◽

Diabetic Mice ◽

Nonalcoholic Fatty Liver

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Jian-Gan-Xiao-Zhi Decoction Alleviates Inflammatory Response in Nonalcoholic Fatty Liver Disease Model Rats through Modulating Gut Microbiota

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5522755 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Jiabao Liao ◽

Xuehua Xie ◽

Jinmei Gao ◽

Zhaiyi Zhang ◽

Fei Qu ◽

...

Keyword(s):

Liver Disease ◽

16S Rrna ◽

Inflammatory Response ◽

Gut Microbiota ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Gut Permeability ◽

16S Rrna Analysis ◽

Nonalcoholic Fatty Liver ◽

Tnf Α

Background. Jian-Gan-Xiao-Zhi decoction (JGXZ), composed of Salvia miltiorrhiza Bunge, Panax notoginseng, Curcuma zedoaria, and other 9 types of herbs, has demonstrated beneficial effects on nonalcoholic fatty liver disease (NAFLD). However, the mechanisms behind JGXZ’s impact on NAFLD remain unknown. Methods. In this study, a NAFLD rat model induced by a high-fat diet (HFD) received oral treatment of JGXZ (8 or 16 g crude herb/kg) for 12 weeks. The therapeutic effects of JGXZ on NAFLD model rats were investigated through blood lipid levels and pathological liver changes. 16S rRNA analysis was used to study the changes in gut microbiota after JGXZ treatment. The expressions of occludin and tight junction protein 1 (ZO-1) in the colon were investigated using immunostaining to study the effects of JGXZ on gut permeability. The anti-inflammatory effects of JGXZ were also studied through measuring the levels of IL-1β, IL-6, and TNF-α in the serum and liver. Results. JGXZ treatment could decrease body weight and ameliorate dyslipidemia in NAFLD model rats. H&E and Oil Red O staining indicated that JGXZ reduced steatosis and infiltration of inflammatory cells in the liver. 16S rRNA analysis showed that JGXZ impacted the diversity of gut microbiota, decreasing the Firmicutes–to-Bacteroidetes ratio, and increasing the relative abundance of probiotics, such as Alloprevotella, Lactobacillus, and Turicibacter. Gut permeability evaluation found that the expressions of ZO-1 and occludin in the colon were increased after JGXZ treatment. Moreover, JGXZ treatment could decrease the levels of IL-1β, IL-6, and TNF-α in the serum and liver. Conclusions. Our study illustrated that JGXZ could ameliorate NAFLD through modulating gut microbiota, decreasing gut permeability, and alleviating inflammatory response.

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Features of a necrotic and inflammatory process in different forms of nonalcoholic fatty liver disease

Terapevticheskii arkhiv ◽

10.17116/terarkh201789252-58 ◽

2017 ◽

Vol 89 (2) ◽

pp. 52-58 ◽

Cited By ~ 2

Author(s):

I V Kurbatova ◽

O P Dudanova

Keyword(s):

Gene Expression ◽

Liver Disease ◽

Fatty Liver ◽

Proinflammatory Cytokines ◽

Fatty Liver Disease ◽

Inflammatory Process ◽

Caspase 3 ◽

Control Group ◽

Nonalcoholic Fatty Liver ◽

Tnf Α

Aim. To identify the features of development of a necrotic and inflammatory process in different forms of nonalcoholic fatty liver disease (NAFLD), by comparatively analyzing a full set of clinical and laboratory parameters, including the cytokine status and the expression level of enzyme genes controlling the apoptosis of peripheral leukocytes. Subjects and methods 86 patients with NAFLD, including 8 (9.3%) with hepatic steatosis (HS), 70 (81.4%) with nonalcoholic steatohepatitis (NASH), 40, 19, and 11 with mild, moderate, and high disease activity, respectively, and 8 (9.3%) with liver cirrhosis (LC), were examined. A control group consisted of 34 healthy donors. Clinical and biochemical blood indices, cytokine profile, and the level of caspase gene transcripts in the peripheral blood leukocytes (PBL) were estimated. Results. As compared to the controls, the patients with HS had higher tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) levels and lower caspase 3, 6, and 8 mRNA in PBL. The concentration of IL-10 in NASH was higher than that in steatosis and positively correlated with the level of proinflammatory cytokines. The levels of TNF-α and IL6 were higher in the patients with NASH than in the controls. Those of C-reactive protein, γ-globulin, IL-6, and cytokeratin-18 fragment increased with the progression of NASH. In the latter, the transcriptional activity of caspase-3 gene decreased relative to the reference value and negatively correlated with the level of proinflammatory cytokines. In the patients with LC, the gene expression profile of caspases in PBL was similar to that in the control group; the level of IL-6 was higher than that in steatosis and NASH, that of IL-1β was higher than in HS and positively correlated the concentration of IL-6 and the activity of alanine aminotransferase and aspartate aminotransferase. Conclusion. The features of a necrotic and inflammatory process were identified in different forms of NAFLD. When the latter progressed, the cytokine profile and gene expression levels of caspases in PBL altered along with a change in the general clinical picture.

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