Characterization of two types of intranuclear hepatocellular inclusions in NAFLD

Schwertheim, Suzan; Kälsch, Julia; Jastrow, Holger; Schaefer, Christoph; Theurer, Sarah; Ting, Saskia; Canbay, Ali; Wedemeyer, Heiner; Schmid, Kurt Werner; Baba, Hideo A.

doi:10.1038/s41598-020-71646-y

Cited by 13 publications

(12 citation statements)

References 40 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The hepatic inflammation was confirmed by morphological analyses showing in BTBR mice liver damage characterized by steatosis, an increase in Kupffer cells, and numerous ultrastructural alterations (i.e., crenulate nucleus, nuclear inclusions, hypertrophic nucleoli, and congested rough ER). Nuclear inclusions are a common finding in hepatocytes with liver diseases, including non-alcoholic fatty liver disease [ 51 , 52 ], but they are also associated with the aging process [ 53 ]. We hypothesized that congested RER in the liver of BTBR mice is linked to ER stress.…”

Section: Discussionmentioning

confidence: 99%

The Hepatic Mitochondrial Alterations Exacerbate Meta-Inflammation in Autism Spectrum Disorders

et al. 2022

View full text Add to dashboard Cite

The role of the liver in autism spectrum disorders (ASD), developmental disabilities characterized by impairments in social interactions and repetitive behavioral patterns, has been poorly investigated. In ASD, it has been shown a dysregulation of gut–brain crosstalk, a communication system able to influence metabolic homeostasis, as well as brain development, mood and cognitive functions. The liver, with its key role in inflammatory and metabolic states, represents the crucial metabolic organ in this crosstalk. Indeed, through the portal vein, the liver receives not only nutrients but also numerous factors derived from the gut and visceral adipose tissue, which modulate metabolism and hepatic mitochondrial functions. Here, we investigated, in an animal model of ASD (BTBR mice), the involvement of hepatic mitochondria in the regulation of inflammatory state and liver damage. We observed increased inflammation and oxidative stress linked to hepatic mitochondrial dysfunction, steatotic hepatocytes, and marked mitochondrial fission in BTBR mice. Our preliminary study provides a better understanding of the pathophysiology of ASD and could open the way to identifying hepatic mitochondria as targets for innovative therapeutic strategies for the disease.

show abstract

Section: Discussionmentioning

confidence: 99%

The Hepatic Mitochondrial Alterations Exacerbate Meta-Inflammation in Autism Spectrum Disorders

et al. 2022

View full text Add to dashboard Cite

show abstract

“…By 28dpi, periportal and intraparenchymal inflammation was noted and hepatic nuclear inclusions (Fig. S13 Inset), known to be associated with liver disease such as hepatocellular carcinoma and non-alcoholic fatty liver disease, were observed 22,23 . In addition, karyomegaly (i.e.…”

Section: Resultsmentioning

confidence: 99%

Host genetic variation guides hepacivirus clearance, chronicity, and liver fibrosis in mice

Brown

Won

Wolfisberg

et al. 2023

Preprint

View full text Add to dashboard Cite

Background & Aims: Human genetic variation is thought to guide the outcome of hepatitis C virus (HCV) infection but model systems within which to dissect these host genetic mechanisms are limited. Norway rat hepacivirus (NrHV), closely related to HCV, causes chronic liver infection in rats but causes acute self-limiting hepatitis in typical strains of laboratory mice, which resolves in two weeks. The Collaborative Cross (CC) is a robust mouse genetics resource comprised of a panel of recombinant inbred strains, which model the complexity of the human genome and provide a system within which to understand diseases driven by complex allelic variation. Approach & Results: We infected a panel of CC strains with NrHV and identified several that failed to clear virus after 4 weeks. Strains displayed an array of virologic phenotypes ranging from delayed clearance (CC046) to chronicity (CC071, CC080) with viremia for at least 10 months. Body weight loss, hepatocyte infection frequency, viral evolution, T-cell recruitment to the liver, liver inflammation and the capacity to develop liver fibrosis varied among infected CC strains. Conclusions: These models recapitulate many aspects of HCV infection in humans and demonstrate that host genetic variation affects a multitude of virus and host phenotypes. These models can be used to better understand the molecular mechanisms that drive hepacivirus clearance and chronicity, the virus and host interactions that promote chronic disease manifestations like liver fibrosis, therapeutic and vaccine performance, and how these factors are affected by host genetic variation.

show abstract

“…It is important to mention, that in the histology of NAFLD, besides steatosis, inflammation, and fibrosis, hepatocellular glycogenated nuclei are also often described, facilitating differentiation between NASH and alcoholic steatohepatitis, since they are rarely seen in the latter ( Pinto et al, 1996 ; Takahashi and Fukusato, 2014 ). Furthermore, the occurrence of glycogenated nuclei in NAFLD cases is associated with disease progression, which may be reflected in the number of cases of concomitant NASH in GlyH case reports ( Table 1 ) ( Schwertheim et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Hepatopathy Associated With Type 1 Diabetes: Distinguishing Non-alcoholic Fatty Liver Disease From Glycogenic Hepatopathy

et al. 2021

View full text Add to dashboard Cite

Autoimmune destruction of pancreatic β-cells results in the permanent loss of insulin production in type 1 diabetes (T1D). The daily necessity to inject exogenous insulin to treat hyperglycemia leads to a relative portal vein insulin deficiency and potentiates hypoglycemia which can induce weight gain, while daily fluctuations of blood sugar levels affect the hepatic glycogen storage and overall metabolic control. These, among others, fundamental characteristics of T1D are associated with the development of two distinct, but in part clinically similar hepatopathies, namely non-alcoholic fatty liver disease (NAFLD) and glycogen hepatopathy (GlyH). Recent studies suggest that NAFLD may be increasingly common in T1D because more people with T1D present with overweight and/or obesity, linked to the metabolic syndrome. GlyH is a rare but underdiagnosed complication hallmarked by extremely brittle metabolic control in, often young, individuals with T1D. Both hepatopathies share clinical similarities, troubling both diagnosis and differentiation. Since NAFLD is increasingly associated with cardiovascular and chronic kidney disease, whereas GlyH is considered self-limiting, awareness and differentiation between both condition is important in clinical care. The exact pathogenesis of both hepatopathies remains obscure, hence licensed pharmaceutical therapy is lacking and general awareness amongst physicians is low. This article aims to review the factors potentially contributing to fatty liver disease or glycogen storage disruption in T1D. It ends with a proposal for clinicians to approach patients with T1D and potential hepatopathy.

show abstract

Characterization of two types of intranuclear hepatocellular inclusions in NAFLD

Cited by 13 publications

References 40 publications

The Hepatic Mitochondrial Alterations Exacerbate Meta-Inflammation in Autism Spectrum Disorders

The Hepatic Mitochondrial Alterations Exacerbate Meta-Inflammation in Autism Spectrum Disorders

Host genetic variation guides hepacivirus clearance, chronicity, and liver fibrosis in mice

Hepatopathy Associated With Type 1 Diabetes: Distinguishing Non-alcoholic Fatty Liver Disease From Glycogenic Hepatopathy

Contact Info

Product

Resources

About