scholarly journals Influencing Factors and Molecular Pathogenesis of Sarcopenia and Osteosarcopenia in Chronic Liver Disease

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 899
Author(s):  
Chisato Saeki ◽  
Akihito Tsubota
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Molecular Mechanisms ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Chronic Liver ◽  
Hormone Regulation ◽  
Anabolic Hormone ◽  
Impaired Liver Function ◽  
And Function

The liver plays a pivotal role in nutrient/energy metabolism and storage, anabolic hormone regulation, ammonia detoxification, and cytokine production. Impaired liver function can cause malnutrition, hyperammonemia, and chronic inflammation, leading to an imbalance between muscle protein synthesis and proteolysis. Patients with chronic liver disease (CLD) have a high prevalence of sarcopenia, characterized by progressive loss of muscle mass and function, affecting health-related quality of life and prognosis. Recent reports have revealed that osteosarcopenia, defined as the concomitant occurrence of sarcopenia and osteoporosis, is also highly prevalent in patients with CLD. Since the differentiation and growth of muscles and bones are closely interrelated through mechanical and biochemical communication, sarcopenia and osteoporosis often progress concurrently and affect each other. Osteosarcopenia further exacerbates unfavorable health outcomes, such as vertebral fracture and frailty. Therefore, a comprehensive assessment of sarcopenia, osteoporosis, and osteosarcopenia, and an understanding of the pathogenic mechanisms involving the liver, bones, and muscles, are important for prevention and treatment. This review summarizes the molecular mechanisms of sarcopenia and osteosarcopenia elucidated to data in hopes of promoting advances in treating these musculoskeletal disorders in patients with CLD.

scholarly journals Sarcopenia in Chronic Liver Disease: Mechanisms and Countermeasures

2020 ◽  
Author(s):  
Sophie Louise Allen ◽  
Jonathan I Quinlan ◽  
Amritpal Dhaliwal ◽  
Matthew J. Armstrong ◽  
Ahmed M Elsharkawy ◽  
...  
Keyword(s):  
Liver Disease ◽  
Amino Acid ◽  
Chronic Liver Disease ◽  
Molecular Mechanisms ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Chronic Liver ◽  
Amino Acid Supplementation ◽  
Skeletal Muscle Index ◽  
Age Related

Sarcopenia, a condition of low muscle mass, quality and strength, is commonly found in cirrhotic patients and is associated with adverse clinical outcomes including: reduction in quality of life, increased mortality and post-transplant complications. In chronic liver disease (CLD) it is most commonly defined through the measurement of the skeletal muscle index of the third lumbar spine. A major contributor to sarcopenia in CLD is the imbalance in muscle protein turnover, which likely occurs due to a decrease in muscle protein synthesis and an elevation in muscle protein breakdown. This imbalance is assumed to arise due to a number of factors including: accelerated starvation, hyperammonemia, amino acid deprivation, chronic inflammation, excessive alcohol intake and physical inactivity. In particular, hyperammonemia is a key mediator of the liver-gut axis and is known to contribute to mitochondrial dysfunction and an increase in myostatin expression. Currently, the use of late-evening snacks, branched-chain amino acid supplementation and physical activity have been proposed to help the management and treatment of sarcopenia. However, little evidence exists to comprehensively support their use in clinical settings. A number of new, pharmacological strategies, including myostatin inhibition and the nutraceutical Urolithin A have recently been proposed to treat age-related sarcopenia, and may also be of use in CLD. This review highlights the potential molecular mechanisms contributing to sarcopenia in CLD alongside a discussion of existing and potential new treatment strategies.

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.

scholarly journals Expression and Function of Methylthioadenosine Phosphorylase in Chronic Liver Disease

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e80703 ◽  
Author(s):  
Barbara Czech ◽  
Katja Dettmer ◽  
Daniela Valletta ◽  
Michael Saugspier ◽  
Andreas Koch ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Methylthioadenosine Phosphorylase ◽  
And Function

Gastroenterology

2019 ◽  
Author(s):  
Ricky Sinharay
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Hospital Admissions ◽  
Medical Profession ◽  
Therapeutic Endoscopy ◽  
Chronic Liver ◽  
Molecular Events ◽  
Related Liver Disease ◽  
The Uk ◽  
And Function

Gastroenterology and hepatology encompass a vast array of organs that have diverse structure and function and are affected by a multitude of disease processes. Diseases of the digestive tract are a major cause of morbidity and mortality in the United Kingdom (UK) and worldwide. There have been great advances in our understanding, diagnosis, and management of gastrointestinal (GI) disease, and knowledge continues to develop at a great pace. Understanding the physiology and cellular and molecular events that drive pathological processes, as well as the devel­opment of sophisticated endoscopic and radiological tests, have trans­formed diagnostic capability. Therapeutic endoscopy has progressed to replace surgical management of common GI emergencies such as upper GI tract bleeding and decompressing biliary tract obstruction. However, as ever, there is still much work to be done. For example, the advances in biologic immunotherapy in inflammatory bowel disease has greatly im­proved patients’ quality of life and a reduction in the need for surgery, though the overall impact of these medications on the natural history of the disease is debatable at present. Hepatology is a greatly misunderstood specialty. The physiological changes that occur as cirrhosis and portal hypertension develop are the key to understanding all manifestations of a decompensating liver. Recently, there has been a significant increase in the prevalence of chronic liver disease in the UK, and as a result, hospital admissions have increased. Liver disease is the only major cause of death still increasing year on year, and twice as many people now die from liver disease than in 1991. The 2013 National Confidential Enquiry into Patient Outcome and Death (NCEPOD) of patients with alcohol- related liver disease (ARLD) found that less than half the number of patients who died from ARLD received ‘good care’, and avoidable deaths were identified. Allied to this, the enquiry shed light on a cultural pessimism regarding outcomes and prognosis of chronic liver disease and, in particular, ARLD from both the public and the medical profession as a whole. There is now a concerted drive towards improving awareness of chronic liver disease, and initial simple supportive treatments can greatly improve sur­vival, more so than previously thought.

scholarly journals LncRNAs Act as a Link between Chronic Liver Disease and Hepatocellular Carcinoma

2020 ◽  
Vol 21 (8) ◽  
pp. 2883
Author(s):  
Young-Ah Kim ◽  
Kwan-Kyu Park ◽  
Sun-Jae Lee
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Hepatic Fibrosis ◽  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Nonalcoholic Fatty Liver ◽  
Underlying Mechanisms

Long non-coding RNAs (lncRNAs) are emerging as important contributors to the biological processes underlying the pathophysiology of various human diseases, including hepatocellular carcinoma (HCC). However, the involvement of these molecules in chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and viral hepatitis, has only recently been considered in scientific research. While extensive studies on the pathogenesis of the development of HCC from hepatic fibrosis have been conducted, their regulatory molecular mechanisms are still only partially understood. The underlying mechanisms related to lncRNAs leading to HCC from chronic liver diseases and cirrhosis have not yet been entirely elucidated. Therefore, elucidating the functional roles of lncRNAs in chronic liver disease and HCC can contribute to a better understanding of the molecular mechanisms, and may help in developing novel diagnostic biomarkers and therapeutic targets for HCC, as well as in preventing the progression of chronic liver disease to HCC. Here, we comprehensively review and briefly summarize some lncRNAs that participate in both hepatic fibrosis and HCC.

scholarly journals Review article: blood platelet number and function in chronic liver disease and cirrhosis

2008 ◽  
Vol 27 (11) ◽  
pp. 1017-1029 ◽  
Author(s):  
P. WITTERS ◽  
K. FRESON ◽  
C. VERSLYPE ◽  
K. PEERLINCK ◽  
M. HOYLAERTS ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Blood Platelet ◽  
Review Article ◽  
Chronic Liver ◽  
Platelet Number ◽  
And Function

scholarly journals The Gut Microbiota-Derived Immune Response in Chronic Liver Disease

2021 ◽  
Vol 22 (15) ◽  
pp. 8309
Author(s):  
Sung-Min Won ◽  
Eunju Park ◽  
Jin-Ju Jung ◽  
Raja Ganesan ◽  
Haripriya Gupta ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Causative Factor ◽  
Chronic Liver ◽  
Intestinal Microbiome ◽  
Future Research ◽  
The Future ◽  
Future Research Directions ◽  
Excessive Intake ◽  
And Function

In chronic liver disease, the causative factor is important; however, recently, the intestinal microbiome has been associated with the progression of chronic liver disease and the occurrence of side effects. The immune system is affected by the metabolites of the microbiome, and diet is the primary regulator of the microbiota composition and function in the gut–liver axis. These metabolites can be used as therapeutic material, and postbiotics, in the future, can increase or decrease human immunity by modulating inflammation and immune reactions. Therefore, the excessive intake of nutrients and the lack of nutrition have important effects on immunity and inflammation. Evidence has been published indicating that microbiome-induced chronic inflammation and the consequent immune dysregulation affect the development of chronic liver disease. In this research paper, we discuss the overall trend of microbiome-derived substances related to immunity and the future research directions.

scholarly journals An Overview of the Molecular Mechanisms Contributing to Musculoskeletal Disorders in Chronic Liver Disease: Osteoporosis, Sarcopenia, and Osteoporotic Sarcopenia

2021 ◽  
Vol 22 (5) ◽  
pp. 2604
Author(s):  
Young Joo Yang ◽  
Dong Joon Kim
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Musculoskeletal Disorders ◽  
Molecular Mechanisms ◽  
Chronic Liver ◽  
Pathophysiological Mechanism ◽  
Alcoholic Fatty Liver ◽  
Receptor Activator ◽  
Branched Chain ◽  
Prevalence Of Osteoporosis

The prevalence of osteoporosis and sarcopenia is significantly higher in patients with liver disease than in those without liver disease and osteoporosis and sarcopenia negatively influence morbidity and mortality in liver disease, yet these musculoskeletal disorders are frequently overlooked in clinical practice for patients with chronic liver disease. The objective of this review is to provide a comprehensive understanding of the molecular mechanisms of musculoskeletal disorders accompanying the pathogenesis of liver disease. The increased bone resorption through the receptor activator of nuclear factor kappa (RANK)-RANK ligand (RANKL)-osteoprotegerin (OPG) system and upregulation of inflammatory cytokines and decreased bone formation through increased bilirubin and sclerostin and lower insulin-like growth factor-1 are important mechanisms for osteoporosis in patients with liver disease. Sarcopenia is associated with insulin resistance and obesity in non-alcoholic fatty liver disease, whereas hyperammonemia, low amount of branched chain amino acids, and hypogonadism contributes to sarcopenia in liver cirrhosis. The bidirectional crosstalk between muscle and bone through myostatin, irisin, β-aminoisobutyric acid (BAIBA), osteocalcin, as well as the activation of the RANK and the Wnt/β-catenin pathways are associated with osteosarcopenia. The increased understandings for these musculoskeletal disorders would be contributes to the development of effective therapies targeting the pathophysiological mechanism involved.

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.

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