ArticleProceedings of the National Academy of Sciences of the United States of America2013
Hyperammonemia in cirrhosis induces transcriptional regulation of myostatin by an NF-κB-mediated mechanism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03285217 (HMB for Denutrition in Patients With Cirrhosis), which is not on this map. Cited by 190 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
HMB for Denutrition in Patients With Cirrhosis (HEPATIC)
Who cites it
190 citing papers in PubMed, 2 syntheses or guidelines pooled it, 276 citations in OpenAlex.
- Association between sarcopenia and hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with cirrhosis: a systematic review and meta-analysis.Abdominal radiology (New York) · 2024Pooled it
- KASL clinical practice guidelines for liver cirrhosis: Varices, hepatic encephalopathy, and related complications.Clinical and molecular hepatology · 2020Guideline
- The effect of a diet based on vegetable and dairy protein on biochemical and functional indicators of sarcopenia in patients with liver cirrhosis: a randomized controlled trial.Nutrition journal · 2025Trial
- Trial
- Metabolic and molecular responses to leucine-enriched branched chain amino acid supplementation in the skeletal muscle of alcoholic cirrhosis.Hepatology (Baltimore, Md.) · 2015Trial
- Revisiting gut microbiota-driven ammonia metabolism: from disease burden to physiological adaptation.Gut microbes · 2026Review
- Voluntary wheel running modulates murine gut microbiome during hyperammonemic stress.Microbiology spectrum · 2026Article
- Review
- Article
- Radiological Assessment of Sarcopenia and Its Association with Metabolic Markers in Patients with Liver Cirrhosis.Journal of clinical medicine · 2026Article
- CT-Quantified Sarcopenic Visceral Obesity Is Negatively Associated with Recompensation in Patients with Decompensated Cirrhosis: A Retrospective Single-Center Study.Journal of clinical medicine · 2026Article
- Covert hepatic encephalopathy in cirrhosis: implications for early diagnosis and appropriate management.Clinical journal of gastroenterology · 2026Review
- Review
- Exposure to Per- and Polyfluoroalkyl Substances and the Risk of Sarcopenia: The Mediating Role of Serum Albumin.Toxics · 2026Article
- Myostatin Research: From Molecular Understanding to Clinical Translation for Musculoskeletal and Metabolic Disorders.International journal of molecular sciences · 2026Review
- Burden of malnutrition and sarcopenia in patients with cirrhosis: pathophysiology, assessment, and management.Clinical and molecular hepatology · 2026Review
- Gut Dysbiosis, Malnutrition and Sarcopenia in Liver Cirrhosis: A Narrative Review.Diseases (Basel, Switzerland) · 2026Review
- Psychomotor Speed From Minimal Hepatic Encephalopathy Testing Is Associated With Physical Frailty in Patients With Advanced Chronic Liver Disease.The American journal of gastroenterology · 2026Article
- Review
- Hyaluronan 35 prevents endotoxin-mediated dysregulated skeletal muscle proteostasis during ethanol exposure.American journal of physiology. Endocrinology and metabolism · 2026Article
130 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Loss of muscle mass, or sarcopenia, is nearly universal in cirrhosis and adversely affects patient outcome. The underlying cross-talk between the liver and skeletal muscle mediating sarcopenia is not well understood. Hyperammonemia is a consistent abnormality in cirrhosis due to impaired hepatic detoxification to urea. We observed elevated levels of ammonia in both plasma samples and skeletal muscle biopsies from cirrhotic patients compared with healthy controls. Furthermore, skeletal muscle from cirrhotics had increased expression of myostatin, a known inhibitor of skeletal muscle accretion and growth. In vivo studies in mice showed that hyperammonemia reduced muscle mass and strength and increased myostatin expression in wild-type compared with postdevelopmental myostatin knockout mice. We postulated that hyperammonemia is an underlying link between hepatic dysfunction in cirrhosis and skeletal muscle loss. Therefore, murine C2C12 myotubes were treated with ammonium acetate resulting in intracellular concentrations similar to those in cirrhotic muscle. In this system, we demonstrate that hyperammonemia stimulated myostatin expression in a NF-κB-dependent manner. This finding was also observed in primary murine muscle cell cultures. Hyperammonemia triggered activation of IκB kinase, NF-κB nuclear translocation, binding of the NF-κB p65 subunit to specific sites within the myostatin promoter, and stimulation of myostatin gene transcription. Pharmacologic inhibition or gene silencing of NF-κB abolished myostatin up-regulation under conditions of hyperammonemia. Our work provides unique insights into hyperammonemia-induced myostatin expression and suggests a mechanism by which sarcopenia develops in cirrhotic patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.