Dataset Information

Nonalcoholic Steatohepatitis is Associated with Cardiac Remodeling and Dysfunction.

ABSTRACT:

Objective

Preliminary data suggest that nonalcoholic fatty liver disease is associated with early heart failure (HF). However, whether nonalcoholic steatohepatitis (NASH) is directly associated with echocardiographic changes in cardiac structure or function remains unknown.

Methods

A retrospective cohort was identified of individuals (N?=?65) without known heart disease, undergoing elective bariatric surgery with perioperative liver biopsy, and available recent transthoracic echocardiography (TTE). TTE measures were evaluated by NASH status using correlation coefficients, ANOVA, and linear regression, accounting for cardiometabolic factors.

Results

Median age was 47 years; 22% (n?=?14) had NASH. NASH patients had increased median left atrial (LA) volume (28.6 mL/m² vs. 24.8 mL/m² ; P?2 vs. 78.6 g/m² ; P?1 ?=?7.16 [SE: 4.95]; P?=?0.001) and LA volume index (ß¹ ?=?0.19 [SE: 0.08]; P?=?0.001) and reduced lateral and septal E' (ß¹ ?=?-0.91, P?=?0.015; ß¹ ?=?-0.89, P?=?0.047, respectively).

Conclusions

In this bariatric cohort, NASH was associated with changes in myocardial structure and in load-dependent indices of LV diastolic function, suggestive of subclinical HF.

SUBMITTER: Simon TG

PROVIDER: S-EPMC5648006 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

Nonalcoholic Steatohepatitis is Associated with Cardiac Remodeling and Dysfunction.

Simon Tracey G TG Bamira Daniel G DG Chung Raymond T RT Weiner Rory B RB Corey Kathleen E KE

Obesity (Silver Spring, Md.) 20170801 8

<h4>Objective</h4>Preliminary data suggest that nonalcoholic fatty liver disease is associated with early heart failure (HF). However, whether nonalcoholic steatohepatitis (NASH) is directly associated with echocardiographic changes in cardiac structure or function remains unknown.<h4>Methods</h4>A retrospective cohort was identified of individuals (N = 65) without known heart disease, undergoing elective bariatric surgery with perioperative liver biopsy, and available recent transthoracic echoc ...[more]

PMID: 28745025

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Project description:Objective: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here we aim to investigate the interaction between adipose tissue and liver in NAFLD, and identify potential early plasma markers that predict NASH. Research Design and Methods: C57Bl/6 mice were chronically fed a high fat diet to induce NAFLD and compared with mice fed low fat diet. Extensive histological and phenotypical analyses coupled with a time-course study of plasma proteins using multiplex assay was performed. Results: Mice exhibited pronounced heterogeneity in liver histological scoring, leading to classification into 4 subgroups: LF-low (LFL) responders displaying normal liver morphology, LF-high (LFH) responders showing benign hepatic steatosis, HF-low (HFL) responders displaying pre-NASH with macrovesicular lipid droplets, and HF-high (HFH) responders exhibiting overt NASH characterized by ballooning of hepatocytes, presence of Mallory bodies, and activated inflammatory cells. Compared to HFL responders, HFH mice gained weight more rapidly and exhibited adipose tissue dysfunction characterized by decreased final fat mass, enhanced macrophage infiltration and inflammation, and adipose tissue remodelling. Plasma haptoglobin, IL-1β, TIMP-1, adiponectin and leptin were significantly changed in HFH mice. Multivariate analysis indicated that in addition to leptin, plasma CRP, haptoglobin, eotaxin and MIP-1α early in the intervention were positively associated with liver triglycerides. Intermediate prognostic markers of liver triglycerides included IL-18, IL-1β, MIP-1γ and MIP-2, whereas insulin, TIMP-1, GCP-2 and MPO emerged as late markers. Conclusions: Our data support the existence of a tight relationship between adipose tissue dysfunction and NASH pathogenesis and point to several novel potential predictive biomarkers for NASH. Keywords: Expression profiling by array Male wildtype C57Bl/6 mice were fed LFD or HFD for 21 weeks. Mice were divided into 4 groups based on liver histology.

Project description:The activated c-Jun N-terminal kinase (JNK) specifically combined with SH3 domain-binding protein 5 (Sab) may mediate damage to the mitochondrial respiratory chain. Whether mitochondrial dysfunction induced by the JNK/Sab signaling pathway plays a pivotal role in the lipotoxic injury of nonalcoholic steatohepatitis (NASH) remains a lack of evidence. Scoparone, a natural compound from Traditional Chinese Medicine herbs, has the potential for liver protection and lipid metabolism regulation. However, the effect of scoparone on NASH induced by a high-fat diet (HFD) as well as its underlying mechanism remains to be elucidated. The HepG2 and Huh7 cells with/without Sab-knockdown induced by palmitic acid (PA) were used to determine the role of JNK/Sab signaling in mitochondrial dysfunction and cellular lipotoxic injury. To observe the effect of scoparone on the lipotoxic injured hepatocytes, different dose of scoparone together with PA was mixed into the culture medium of HepG2 and AML12 cells to incubate for 24 h. In addition, male C57BL/6J mice were fed with an HFD for 22 weeks to induce the NASH model and were treated with scoparone for another 8 weeks to investigate its effect on NASH. Molecules related to JNK/Sab signaling, mitochondrial function, and lipotoxic injury were detected in in vitro and/or in vivo experiments. The results showed that PA-induced activation of JNK/Sab signaling was blocked by Sab knockdown in hepatocytes, which improved mitochondrial damage, oxidative stress, hepatosteatosis, cell viability, and apoptosis. Scoparone demonstrated a similar effect on the PA-induced hepatocytes as Sab knockdown. For the NASH mice, treatment with scoparone also downregulated the activation of JNK/Sab signaling, improved histopathological changes of liver tissues including mitochondrial number and morphology, lipid peroxide content, hepatosteatosis and inflammation obviously, as well as decreased the serum level of lipid and transaminases. Taken together, this study confirms that activation of the JNK/Sab signaling pathway-induced mitochondrial dysfunction plays a crucial role in the development of NASH. Scoparone can improve the lipotoxic liver injury partially by suppressing this signaling pathway, making it a potential therapeutic compound for NASH.

Dataset Information

Nonalcoholic Steatohepatitis is Associated with Cardiac Remodeling and Dysfunction.

Objective

Methods

Results

Conclusions

Publications

Nonalcoholic Steatohepatitis is Associated with Cardiac Remodeling and Dysfunction.

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