scholarly journals Article Commentary: Insulin Resistance, Type 2 Diabetes and Chronic Liver Disease. A Deadly Trio

2009 ◽  
Vol 2 ◽  
pp. CMED.S3518 ◽  
Author(s):  
Amedeo Lonardo ◽  
Paola Loria
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Clinical Medicine ◽  
Morphological Characteristics ◽  
Chronic Liver ◽  
Increased Risk ◽  
History Of

In this commentary to the paper by Donadon V. et al (Clinical Medicine: Endocrinology and Diabetes. 2009;2:25–33.) the association and significance of insulin resistance with chronic liver disease are shortly reviewed and the molecular mechanisms underlying the diabetogenic and oncogenic potentials of advanced liver disease are summarized. Literature studies demonstrate that hepatocellular carcinoma (HCC) can be part of the natural history of NASH. HCCs in patients with features of metabolic syndrome as the only risk factor for liver disease have distinct morphological characteristics and mainly occur in the absence of significant fibrosis in the background liver. Moreover, data indicate that the presence of diabetes carries an approximately three to four-fold increased risk of HCC and such a risk is strongly increased by concurrent viral infections. Finally, the relationship between insulin resistance, steatosis and diabetes in NAFLD and HCV infection will be commented, along with the directions for future studies.

scholarly journals Notch Inhibition Promotes Differentiation of Liver Progenitor Cells into Hepatocytes via sox9b Repression in Zebrafish

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jacquelyn O. Russell ◽  
Sungjin Ko ◽  
Satdarshan P. Monga ◽  
Donghun Shin
Keyword(s):  
Liver Disease ◽  
Liver Regeneration ◽  
Notch Signaling ◽  
Chronic Liver Disease ◽  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Therapeutic Option ◽  
Chronic Liver ◽  
Hepatocyte Proliferation ◽  
Hepatocyte Differentiation

Liver regeneration after most forms of injury is mediated through the proliferation of hepatocytes. However, when hepatocyte proliferation is impaired, such as during chronic liver disease, liver progenitor cells (LPCs) arising from the biliary epithelial cell (BEC) compartment can give rise to hepatocytes to mediate hepatic repair. Promotion of LPC-to-hepatocyte differentiation in patients with chronic liver disease could serve as a potentially new therapeutic option, but first requires the identification of the molecular mechanisms driving this process. Notch signaling has been identified as an important signaling pathway promoting the BEC fate during development and has also been implicated in regulating LPC differentiation during regeneration. SRY-related HMG box transcription factor 9 (Sox9) is a direct target of Notch signaling in the liver, and Sox9 has also been shown to promote the BEC fate during development. We have recently shown in a zebrafish model of LPC-driven liver regeneration that inhibition of Hdac1 activity through MS-275 treatment enhances sox9b expression in LPCs and impairs LPC-to-hepatocyte differentiation. Therefore, we hypothesized that inhibition of Notch signaling would promote LPC-to-hepatocyte differentiation by repressing sox9b expression in zebrafish. We ablated the hepatocytes of Tg(fabp10a:CFP-NTR) larvae and blocked Notch activation during liver regeneration through treatment with γ-secretase inhibitor LY411575 and demonstrated enhanced induction of Hnf4a in LPCs. Alternatively, enhancing Notch signaling via Notch3 intracellular domain (N3ICD) overexpression impaired Hnf4a induction. Hepatocyte ablation in sox9b heterozygous mutant embryos enhanced Hnf4a induction, while BEC-specific Sox9b overexpression impaired LPC-to-hepatocyte differentiation. Our results establish the Notch-Sox9b signaling axis as inhibitory to LPC-to-hepatocyte differentiation in a well-established in vivo LPC-driven liver regeneration model.

NATURAL HISTORY OF HEPATITIS-ASSOCIATED ANTIGEN-POSITIVE CHRONIC LIVER DISEASE

The Lancet ◽  
1972 ◽  
Vol 300 (7792) ◽  
pp. 1388-1393 ◽  
Author(s):  
F.J. Dudley ◽  
P.J. Scheuer ◽  
S. Sherlock
Keyword(s):  
Liver Disease ◽  
Natural History ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
History Of

MON-PP063: Contribution of Selenium Deficiency to Insulin Resistance in Patients with HCV-Related Chronic Liver Disease

2015 ◽  
Vol 34 ◽  
pp. S151
Author(s):  
T. Himoto ◽  
T. Nomura ◽  
J. Tani ◽  
H. Miyoshi ◽  
A. Morishita ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Selenium Deficiency ◽  
Chronic Liver

Association of tyrosine with insulin resistance in hepatitis C virus-related chronic liver disease

2013 ◽  
Vol 44 (10) ◽  
pp. E54-E62 ◽  
Author(s):  
Takashi Oono ◽  
Takahiro Yamasaki ◽  
Junichi Zaitsu ◽  
Issei Saeki ◽  
Takuya Iwamoto ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Chronic Liver Disease ◽  
Chronic Liver

Increased Risk of Chronic Liver Disease in Patients with Schizophrenia: A Population-Based Cohort Study

2014 ◽  
Vol 55 (2) ◽  
pp. 163-171 ◽  
Author(s):  
Jer-Hwa Hsu ◽  
I-Chia Chien ◽  
Ching-Heng Lin ◽  
Yiing-Jenq Chou ◽  
Pesus Chou
Keyword(s):  
Cohort Study ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Population Based ◽  
Chronic Liver ◽  
Increased Risk

637 FAS/FASL system and IL-1β in the natural history of chronic liver disease from hepatitis to cancer

Hepatology ◽  
2003 ◽  
Vol 38 ◽  
pp. 467-467
Author(s):  
M BORTOLAMI ◽  
H WALDNER ◽  
C VENTURI ◽  
R CARDIN ◽  
C CARLOTTO ◽  
...  
Keyword(s):  
Liver Disease ◽  
Natural History ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
History Of

scholarly journals The impact of endotrophin on the progression of chronic liver disease

2020 ◽  
Vol 52 (10) ◽  
pp. 1766-1776
Author(s):  
Min Kim ◽  
Changhu Lee ◽  
Dae Yun Seo ◽  
Hyojung Lee ◽  
Jay D. Horton ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Insulin Resistance ◽  
Liver Disease ◽  
Liver Cancer ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Hepatic Inflammation ◽  
Fibrotic Liver ◽  
Alcoholic Fatty Liver ◽  
The Impact

Abstract Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and can lead to multiple complications, including non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. The fibrotic liver is characterized by the pathological accumulation of extracellular matrix (ECM) proteins. Type VI collagen alpha3 (Col6a3) is a biomarker of hepatic fibrosis, and its cleaved form, endotrophin (ETP), plays a critical role in adipose tissue dysfunction, insulin resistance, and breast cancer development. Here, we studied the effects of the Col6a3-derived peptide ETP on the progression of chronic liver diseases, such as NASH and liver cancer. We used a doxycycline (Dox)-inducible liver-specific ETP-overexpressing mouse model on a NAFLD-prone (liver-specific SREBP1a transgenic) background. For this, we evaluated the consequences of local ETP expression in the liver and its effect on hepatic inflammation, fibrosis, and insulin resistance. Accumulation of ETP in the liver induced hepatic inflammation and the development of fibrosis with associated insulin resistance. Surprisingly, ETP overexpression also led to the emergence of liver cancer within 10 months in the SREBP1a transgenic background. Our data revealed that ETP can act as a “second hit” during the progression of NAFLD and can play an important role in the development of NASH and hepatocellular carcinoma (HCC). These observations firmly link elevated levels of ETP to chronic liver disease.

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