Bile acids aggravate nonalcoholic steatohepatitis and cardiovascular disease in SHRSP5/Dmcr rat model

Yamamoto, Sadaki; Sato, Ikumi; Fukuhama, Natsuki; Akiyama, Natsumi; Sakai, Miku; Kumazaki, Shota; Ran, Shang; Hirohata, Satoshi; Kitamori, Kazuya; Yamori, Yukio; Watanabe, Shozo

doi:10.1016/j.yexmp.2020.104437

Cited by 11 publications

(6 citation statements)

References 42 publications

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“…Our findings of a close association between conjugated BA, LAVI and septal e ′ could indicate that BA signalling is involved in the underlying pathology of diastolic dysfunction. Some experimental studies have reported that excessive BA promote structural myocardial changes, including diffuse fibrosis and hypertrophy 6,14 . Although we did find increased total BA and conjugated BA levels in patients with increased myocardial ECV, the correlations between the BA composition, myocardial ECV and myocardial mass were weak and disappeared when adjusted for MELD score.…”

Section: Discussioncontrasting

confidence: 86%

“…Some experimental studies have reported that excessive BA promote structural myocardial changes, including diffuse fibrosis and hypertrophy. 6,14 Although we did find increased total BA and conjugated BA levels in patients with increased myocardial ECV, the correlations between the BA composition, myocardial ECV and myocardial mass were weak and disappeared when adjusted for MELD score. Hence, the relationship between the BA composition and diastolic dysfunction cannot be explained by BA-induced structural myocardial changes.…”

Section: Lowmentioning

confidence: 57%

“…They showed an aggravation of NASH and cardiovascular disease when rats were fed a diet with increasing BA concentrations. Furthermore, they reported left ventricular dysfunction and myocardial fibrosis, as well as severe hepatic fibrosis, in rats receiving the highest amounts of BA 14 . We have previously investigated the relationship between serum total BA and cardiac dysfunction in cirrhosis in a study using echocardiography and found close associations between increased concentrations of total BA, cardiac output and left atrial volume 8 .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, they reported left ventricular dysfunction and myocardial fibrosis, as well as severe hepatic fibrosis, in rats receiving the highest amounts of BA. 14 We have previously investigated the relationship between serum total BA and cardiac dysfunction in cirrhosis in a study using echocardiography and found close associations between increased concentrations of total BA, cardiac output and left atrial volume. 8 In the current study, we included cardiac MRI, which is the gold standard for assessing structural and functional cardiac abnormalities, and we analysed a broad panel of serum BA to add granularity to our previous findings.…”

Section: Discussionmentioning

confidence: 99%

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Altered serum bile acid composition is associated with cardiac dysfunction in cirrhosis

Wiese

Danielsen

Busk

et al. 2023

Aliment Pharmacol Ther

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Background: Elevated serum bile acids (BA) are harmful to the heart and alterations in the BA composition have been suggested to cause cardiovascular disturbances in cirrhosis. Aim: To investigate any associations between specific groups or individual serum BA and structural and functional cardiac abnormalities in patients with cirrhosis. Methods: An explorative study in 86 patients with cirrhosis. All participants underwent extensive cardiac assessment, including cardiac MRI with quantification of myocardial extracellular volume (ECV), which is indicative of diffuse myocardial fibrosis. A panel of 15 individual serum BA and C4, a marker of de novo bile acid synthesis, were assessed.Results: Patients with advanced cirrhosis had higher levels of total BA and conjugated BA, as well as lower C4 levels (p < 0.001). Conjugated BA levels were higher in patients with a high cardiac index (p < 0.001), increased left atrial volume index (LAVI) (p < 0.001), and in those with an abnormal myocardial ECV (p < 0.05). We also found several strong correlations between conjugated BA, both as a group and individually, and parameters of cardiac dysfunction. In a model adjusted for sex, age, BMI and MELD, conjugated BA remained significantly associated with LAVI, septal e′, left ventricular volumes and cardiac index. In addition, taurocholic acid correlated closely with hepatic venous pressure gradient (HVPG) (p = 0.01). Conclusions: Increased serum concentrations of conjugated BA are associated with several cardiac parameters, indicating a potential role in the development of hyperdynamic circulation and cardiac dysfunction in cirrhosis. Moreover, taurine-conjugated BA are associated with portal hypertension.

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Section: Discussioncontrasting

confidence: 86%

Section: Lowmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Altered serum bile acid composition is associated with cardiac dysfunction in cirrhosis

Wiese

Danielsen

Busk

et al. 2023

Aliment Pharmacol Ther

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“… 2019 ; Yamamoto et al. 2020 ). IL-1β and −6 are classic indicators of inflammation, and TNFα is a pro-inflammatory factor produced by macrophages, which can stimulate monocytes and neutrophils to secrete IL-1β and −6 (Chaudhari and Kumar 2020 ; Fouad et al.…”

Section: Discussionmentioning

confidence: 99%

Swertia mussotii prevents high-fat diet-induced non-alcoholic fatty liver disease in rats by inhibiting expression the TLR4/MyD88 and the phosphorylation of NF-κB

Dong

Cheng

et al. 2022

Pharmaceutical Biology

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Context Swertia mussotii Franch. (Gentianaceae) is a source of the traditional Tibetan medicine, ZangYinChen, and is used to treat chronic hepatitis and many types of jaundice. Objective This study explored the therapeutic effects and mechanism of S. mussotii on non-alcoholic fatty liver disease in diet-induced hypercholesterolaemia. Materials and methods After a week of adaptive feeding, 32 Sprague-Dawley rats were divided into four groups: (1) Control, (2) Control-S, (3) Model, and (4) Model-S. During the 12 experimental weeks, we established the Model using a high-fat diet. Control-S and Model-S were given 1.0 g/kg S. mussotii water extract via gavage starting in the fifth week until the end of experiment. Results When compared with Model rats, the S. mussotii water extract led to a reduction in high-density lipoproteins (43.9%) and albumin (13.9%) and a decrease in total cholesterol (54.0%), triglyceride (45.6%), low-density lipoproteins (8.6%), aspartate aminotransferase (11.0%), alanine aminotransferase (15.5%), alkaline phosphatase (19.1%), total protein (6.4%), and glucose (20.8%) in serum. A reduction in three cytokines (IL-1β, IL-6, and TNFα) was detected. Histopathological examination showed that liver steatosis was significantly relieved in S. mussotii -treated high-fat diet rats. S. mussotii also caused a downregulation in the expression of TLR4 (43.2%), MyD88 (33.3%), and a decrease in phosphorylation of NF-κB. Discussion and conclusions Our findings indicate that S. mussotii may act as a potential anti-inflammation drug via inhibition of the TLR4/MyD88/NF-κB pathway. Further in vivo and in vitro studies are needed to validate its potential in clinical medicine.

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Farnesoid X receptor (FXR) agonists induce hepatocellular apoptosis and impair hepatic functions via FXR/SHP pathway

Zhang

Feng²,

et al. 2022

Arch Toxicol

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Bile acids aggravate nonalcoholic steatohepatitis and cardiovascular disease in SHRSP5/Dmcr rat model

Cited by 11 publications

References 42 publications

Altered serum bile acid composition is associated with cardiac dysfunction in cirrhosis

Altered serum bile acid composition is associated with cardiac dysfunction in cirrhosis

Swertia mussotii prevents high-fat diet-induced non-alcoholic fatty liver disease in rats by inhibiting expression the TLR4/MyD88 and the phosphorylation of NF-κB

Farnesoid X receptor (FXR) agonists induce hepatocellular apoptosis and impair hepatic functions via FXR/SHP pathway

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