ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2010
BCATm deficiency ameliorates endotoxin-induced decrease in muscle protein synthesis and improves survival in septic mice.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Branched-chain amino acids and sepsis: from pathological mechanisms to clinical interventions.Nutrition & metabolism · 2025Review
- Polyacrylic acid, but not polyethylene glycol, induces metabolic reprogramming linked to pulmonary fibrosis in rats.Scientific reports · 2025Article
- Evaluating skeletal muscle wasting and weakness in models of critical illness.Clinical science (London, England : 1979) · 2025Review
- Genotypic and phenotypic spectrum of maple syrup urine disease in Zhejiang of China.QJM : monthly journal of the Association of Physicians · 2024Article
- The mechanism of branched-chain amino acid transferases in different diseases: Research progress and future prospects.Frontiers in oncology · 2022Review
- Article
- Clinical, Biochemical, Molecular, and Therapeutic Analysis of Maple Syrup Urine Disease in Upper Egypt.Journal of pediatric genetics · 2021Article
- Effect of policosanol from insect wax on amyloid β-peptide-induced toxicity in a transgenic Caenorhabditis elegans model of Alzheimer's disease.BMC complementary medicine and therapies · 2021Article
- Frontline Science: Monocytes sequentially rewire metabolism and bioenergetics during an acute inflammatory response.Journal of leukocyte biology · 2019Article
- Post-ruminal branched-chain amino acid supplementation and intravenous lipopolysaccharide infusion alter blood metabolites, rumen fermentation, and nitrogen balance of beef steers.Journal of animal science · 2018Article
- Regulation of Metabolic Disease-Associated Inflammation by Nutrient Sensors.Mediators of inflammation · 2018Review
- A Novel Whole Gene Deletion ofFrontiers in genetics · 2018Article
- Maple syrup urine disease: mechanisms and management.The application of clinical genetics · 2017Review
- Branched-chain amino acid catabolism is a conserved regulator of physiological ageing.Nature communications · 2015Article
- Global deletion of BCATm increases expression of skeletal muscle genes associated with protein turnover.Physiological genomics · 2015Article
- Dysregulation of skeletal muscle protein metabolism by alcohol.American journal of physiology. Endocrinology and metabolism · 2015Review
- Sepsis attenuates the anabolic response to skeletal muscle contraction.Shock (Augusta, Ga.) · 2015Article
- Alcohol intoxication following muscle contraction in mice decreases muscle protein synthesis but not mTOR signal transduction.Alcoholism, clinical and experimental research · 2015Article
- Alcohol impairs skeletal muscle protein synthesis and mTOR signaling in a time-dependent manner following electrically stimulated muscle contraction.Journal of applied physiology (Bethesda, Md. : 1985) · 2014Article
- Abandon the mouse research ship? Not just yet!Shock (Augusta, Ga.) · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Endotoxin (LPS) and sepsis decrease mammalian target of rapamycin (mTOR) activity in skeletal muscle, thereby reducing protein synthesis. Our study tests the hypothesis that inhibition of branched-chain amino acid (BCAA) catabolism, which elevates circulating BCAA and stimulates mTOR, will blunt the LPS-induced decrease in muscle protein synthesis. Wild-type (WT) and mitochondrial branched-chain aminotransferase (BCATm) knockout mice were studied 4 h after Escherichia coli LPS or saline. Basal skeletal muscle protein synthesis was increased in knockout mice compared with WT, and this change was associated with increased eukaryotic initiation factor (eIF)-4E binding protein-1 (4E-BP1) phosphorylation, eIF4E.eIF4G binding, 4E-BP1.raptor binding, and eIF3.raptor binding without a change in the mTOR.raptor complex in muscle. LPS decreased muscle protein synthesis in WT mice, a change associated with decreased 4E-BP1 phosphorylation as well as decreased formation of eIF4E.eIF4G, 4E-BP1.raptor, and eIF3.raptor complexes. In BCATm knockout mice given LPS, muscle protein synthesis only decreased to values found in vehicle-treated WT control mice, and this ameliorated LPS effect was associated with a coordinate increase in 4E-BP1.raptor, eIF3.raptor, and 4E-BP1 phosphorylation. Additionally, the LPS-induced increase in muscle cytokines was blunted in BCATm knockout mice, compared with WT animals. In a separate study, 7-day survival and muscle mass were increased in BCATm knockout vs. WT mice after polymicrobial peritonitis. These data suggest that elevating blood BCAA is sufficient to ameliorate the catabolic effect of LPS on skeletal muscle protein synthesis via alterations in protein-protein interactions within mTOR complex-1, and this may provide a survival advantage in response to bacterial infection.
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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.