Adipokines and Endotoxemia Correlate with Hepatic Steatosis in Non-Alcoholic Fatty Liver Disease (NAFLD)

Nier, Anika; Huber, Yvonne; Labenz, Christian; Michel, Maurice Stephan; Bergheim, Ina; Schattenberg, Jörn M.

doi:10.3390/nu12030699

Cited by 41 publications

(41 citation statements)

References 36 publications

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“…In line with these findings, bacterial endotoxin levels in plasma of NAFLD patients were also significantly higher, all suggesting that intestinal barrier function of NAFLD patients was impaired, and subsequently, translocation of bacterial toxins was increased. These findings are in line with the findings of others and earlier studies of our own group in adults and children with early and progressed signs of the disease all suggesting that the development and progression of NAFLD is associated with changes in intestinal barrier function and an increased translocation of bacterial endotoxin [26][27][28][29] . Somewhat contrasting the findings for bacterial endotoxin and the other markers of intestinal barrier function, LTA levels in plasma were not markedly higher in NAFLD patients; however, we found that data varied considerably and were sort of clustered.…”

Section: Discussionsupporting

confidence: 93%

Toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease

Baumann

Nier

Hernández-Arriaga

et al. 2021

Sci Rep

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Toll-like receptors (TLRs) in the liver compartment have repeatedly been attributed to the development of non-alcoholic fatty liver disease (NAFLD). Knowledge on TLR expression in blood cells and their relation to intestinal microbiota and NAFLD development is limited. Here, we determined TLR expression patterns in peripheral blood mononuclear cells (PBMCs) of NAFLD patients and controls, their relation to intestinal microbiota and the impact of TLRs found altered in NAFLD development. Markers of intestinal permeability in blood and TLR mRNA expression in PBMCs were determined in 37 NAFLD patients and 15 age-matched healthy controls. Fecal microbiota composition was evaluated in 21 NAFLD patients and 9 controls using 16S rRNA gene amplicon sequencing. Furthermore, TLR1−/− and C57BL/6 mice (n = 5–6/group) were pair-fed a liquid control or a fat-, fructose- and cholesterol-rich diet. Intestinal microbiota composition and markers of intestinal permeability like zonulin and bacterial endotoxin differed significantly between groups with the latter markers being significantly higher in NAFLD patients. Expression of TLR1-8 and 10 mRNA was detectable in PBMCs; however, only TLR1 expression, being higher in NAFLD patients, were significantly positively correlated with the prevalence of Holdemanella genus while negative correlations were found with Gemmiger and Ruminococcus genera. TLR1−/− mice were significantly protected from the development of diet-induced NAFLD when compared to wild-type mice. While intestinal microbiota composition and permeability differed significantly between NAFLD patients and healthy subjects, in PBMCs, only TLR1 expression differed between groups. Still, targeting these alterations might be a beneficial approach in the treatment of NAFLD in some patients.

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Section: Discussionsupporting

confidence: 93%

Toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease

Baumann

Nier

Hernández-Arriaga

et al. 2021

Sci Rep

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“…These translocation episodes bring potent immunogenic factors into systemic level, contributing to the global inflammatory burden 39 . The most studied antigen has been bacterial endotoxin, which has shown to be increased in blood of NAFLD patients 33,34 . However, other antigenic products may also reach systemic circulation and have shown their clinical relevance, not only in advanced chronic liver disease 40 but also in other chronic pathologies such as Crohn's disease 41 or morbid obesity 42 …”

Section: Discussionmentioning

confidence: 99%

“…CpG motifs on bacterial DNA, lipopolysaccharide (LPS) derived from gram‐negative bacteria and lipotheicoic acid (LTA) derived from gram‐positive bacteria are recognized by Toll‐like receptor (TLR)‐9, TLR‐4 and TLR2 respectively. Although all three BT have shown to induce the systemic upregulation of soluble inflammatory mediators, 32 only LPS and its correlation with severity of hepatic steatosis has been described in NAFLD patients, 33,34 while the translocation of the other antigens and their contribution in the systemic inflammatory burden of these patients has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Bacterial antigen translocation and age as BMI‐independent contributing factors on systemic inflammation in NAFLD patients

Gómez‐Hurtado

Gallego‐Durán

Zapater

et al. 2020

Liver International

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Background & Aims Low‐grade systemic inflammation is a crucial landmark in NAFLD favouring disease progression and comorbidities. We evaluated the input of circulating bacterial antigens on systemic markers of inflammation in NAFLD patients. Patients & Methods Multicenter cross‐sectional study including consecutive patients with biopsy‐proven NAFLD. Demographic, metabolic and fibrosis‐related variables were collected. Circulating bacterial antigens were quantified in blood. Toll‐like receptor SNPs were genotyped. Serum cytokine levels were evaluated. Peripheral blood mononuclear cell response to bacterial antigens was evaluated in vitro. Results Three hundred and fifteen patients from five Spanish hospitals were distributed by BMI. At least, one bacterial antigenic type was found in 66 patients with BMI < 30 (63.4%) and 163 patients with BMI > 30 (77.3%) (P = .014). HOMA‐IR was significantly higher in the presence of circulating antigens among patients with BMI < 30. NASH and significant fibrosis in non‐obese patients were more frequent in the presence of at least two circulating antigenic types. Allelic frequencies of TLR variants were similar to controls and did not affect clinical or laboratory parameters. Pro‐inflammatory cytokines were significantly increased in patients with bacterial antigens, regardless of BMI. TLR gene and protein expression levels were significantly increased in PBMCs from patients with bacterial antigens. Antigen concentrations independently influenced TNF‐α and IL‐6, in both BMI subgroups of patients. Age independently influenced TNF‐α and IL‐6 in non‐obese patients, and TNF‐α in obese patients. Conclusion Serum circulating bacterial antigens as well as age were BMI‐independent factors related to increased systemic inflammation in NAFLD and provides insight on the multifaceted sources of inflammation in these patients.

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“…Hypothyroid subjects have altered adiponectin levels that can contribute to IR development. The modified adipocytokines registered have hepatotoxic properties, can promote oxygen radical release, and furnish liver inflammation and fibrosis [ 160 , 161 ]. Leptin is one hormone that is in charge of appetite modulation, can promote hepatic collagen synthesis hepatic IR, and is involved in hepatic fibrogenesis [ 162 ].…”

Section: Immunopathogenesismentioning

confidence: 99%

Hypothyroidism-Induced Nonalcoholic Fatty Liver Disease (HIN): Mechanisms and Emerging Therapeutic Options

Gosav

Neculae

Costea

et al. 2020

IJMS

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Nonalcoholic fatty liver disease (NAFLD) is an emerging worldwide problem and its association with other metabolic pathologies has been one of the main research topics in the last decade. The aim of this review article is to provide an up-to-date correlation between hypothyroidism and NAFLD. We followed evidence regarding epidemiological impact, immunopathogenesis, thyroid hormone-liver axis, lipid and cholesterol metabolism, insulin resistance, oxidative stress, and inflammation. After evaluating the influence of thyroid hormone imbalance on liver structure and function, the latest studies have focused on developing new therapeutic strategies. Thyroid hormones (THs) along with their metabolites and thyroid hormone receptor β (THR-β) agonist are the main therapeutic targets. Other liver specific analogs and alternative treatments have been tested in the last few years as potential NAFLD therapy. Finally, we concluded that further research is necessary as well as the need for an extensive evaluation of thyroid function in NAFLD/NASH patients, aiming for better management and outcome.

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Adipokines and Endotoxemia Correlate with Hepatic Steatosis in Non-Alcoholic Fatty Liver Disease (NAFLD)

Cited by 41 publications

References 36 publications

Toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease

Toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease

Bacterial antigen translocation and age as BMI‐independent contributing factors on systemic inflammation in NAFLD patients

Hypothyroidism-Induced Nonalcoholic Fatty Liver Disease (HIN): Mechanisms and Emerging Therapeutic Options

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