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 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.

204 Awardee Talk: Recent Advances in Protein Nutrition in Horses

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 109-109
Author(s):  
Kristine Urschel
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Mass ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Protein Digestibility ◽  
Future Research ◽  
Amino Acid Supplementation ◽  
Protein Nutrition ◽  
Active Research

Abstract Protein has been recognized as an essential nutrient for animals for well over 100 years. Protein plays many important structural and metabolic roles, and some of its component amino acids have additional functions, including as regulatory molecules, as energy substrates and in the synthesis of other non-protein molecules. Skeletal muscle makes up approximately 50% of body weight in horses, with protein being the major non-water component. As an athletic species, the development and maintenance of muscle mass is of the utmost importance in horses. Because muscle mass is largely determined by the balance of rates of muscle protein synthesis and breakdown, understanding how these pathways are regulated and influenced by dietary protein and amino acid provision is essential. Historically, much research regarding protein nutrition in horses has focused on the protein digestibility of different feed ingredients, and the adequacy of different protein sources in supporting the growth and maintenance of horses. This presentation will focus on some of the current areas of active research relating to protein nutrition in horses: the activation of the signaling pathways that regulate muscle protein synthesis, amino acid supplementation in athletic horses, protein metabolism in aged and horses and those with insulin dysregulation, and amino acid and protein nutrition in predominantly forage-fed horses. There are many exciting opportunities for future research in the area of protein and amino acid nutrition in horses across the lifespan.

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 Amino Acid Supplementation Increases Lean Body Mass, Basal Muscle Protein Synthesis, and Insulin-Like Growth Factor-I Expression in Older Women

2009 ◽  
Vol 94 (5) ◽  
pp. 1630-1637 ◽  
Author(s):  
Edgar L. Dillon ◽  
Melinda Sheffield-Moore ◽  
Douglas Paddon-Jones ◽  
Charles Gilkison ◽  
Arthur P. Sanford ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Growth Factor ◽  
Older Women ◽  
Lean Body Mass ◽  
Body Mass ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Amino Acid Supplementation ◽  
Factor I

scholarly journals The relationship between amino acid-nitrogen metabolism and plasma zinc in patients with chronic liver disease.

Kanzo ◽  
2001 ◽  
Vol 42 (3) ◽  
pp. 120-125 ◽  
Author(s):  
Kazuhiro KATAYAMA ◽  
Yuko OOKA ◽  
Sumi KIKKAWA ◽  
Akio UEMURA ◽  
Shinichiro SHINZAKI ◽  
...  
Keyword(s):  
Liver Disease ◽  
Amino Acid ◽  
Chronic Liver Disease ◽  
Nitrogen Metabolism ◽  
Chronic Liver ◽  
Plasma Zinc ◽  
Amino Acid Nitrogen ◽  
The Relationship

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 Does the muscle protein synthetic response to exercise and amino acid-based nutrition diminish with advancing age? A systematic review

2016 ◽  
Vol 311 (5) ◽  
pp. E803-E817 ◽  
Author(s):  
Brandon J. Shad ◽  
Janice L. Thompson ◽  
Leigh Breen
Keyword(s):  
Systematic Review ◽  
Amino Acid ◽  
Acute Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Sufficient Evidence ◽  
Older Individuals ◽  
Anabolic Resistance ◽  
Age Related ◽  
Response To Exercise

The precise role of age-related muscle anabolic resistance in the progression of sarcopenia and functional decline in older individuals is unclear. The present aim was to assess whether the muscle protein synthesis (MPS) response to acute exercise (endurance or resistance) and/or amino acid-based nutrition is attenuated in older compared with young individuals. A systematic review was conducted on studies that directly examined the influence of age on the MPS response to exercise and/or amino acid-based nutrition. Each study arm was synthesized and reported as providing sufficient or insufficient “evidence of age-related muscle anabolic resistance”. Subsequently, three models were established to compare age-related differences in the MPS response to 1) exercise alone, 2) amino acid-based nutrition alone, or 3) the combination of exercise and amino acid-based nutrition. Following exercise alone, 8 of the 17 study arms provided sufficient evidence of age-related muscle anabolic resistance, while in response to amino acid-based nutrition alone, 8 of the 21 study arms provided sufficient evidence of age-related muscle anabolic resistance. When exercise and amino acid-based nutrition were combined, only 2 of the 10 study arms provided sufficient evidence of age-related muscle anabolic resistance. Our results highlight that optimization of exercise and amino acid-based nutrition is sufficient to induce a comparable MPS response between young and older individuals. However, the exercise volume completed and/or the amino acid/protein dose and leucine content must exceed a certain threshold to stimulate equivalent MPS rates in young and older adults, below which age-related muscle anabolic resistance may become apparent.

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