ArticleScientific reports2016
Metformin inhibits Branched Chain Amino Acid (BCAA) derived ketoacidosis and promotes metabolic homeostasis in MSUD.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 57 citations in OpenAlex.
- Plasma metabolomic profiling reveals metabolic shifts linked to growth depression in broilers fed high level of valine.Poultry science · 2026Article
- Lipodystrophy in methylmalonic acidemia associated with elevated FGF21 and abnormal methylmalonylation.JCI insight · 2024Article
- Targeting Glycolytic Reprogramming in Cholangiocarcinoma: A Novel Approach for Metabolic Therapy.Journal of inflammation research · 2024Review
- Branched-Chain Amino Acid Assembly into Amyloid-like Fibrils Provides a New Paradigm for Maple Syrup Urine Disease Pathology.International journal of molecular sciences · 2023Article
- Depiction of Branched-Chain Amino Acids (BCAAs) in Diabetes with a Focus on Diabetic Microvascular Complications.Journal of clinical medicine · 2023Review
- Metabolomic profiles of metformin in breast cancer survivors: a pooled analysis of plasmas from two randomized placebo-controlled trials.Journal of translational medicine · 2022Article
- Neonatal gene therapy achieves sustained disease rescue of maple syrup urine disease in mice.Nature communications · 2022Article
- Immunometabolism - The Role of Branched-Chain Amino Acids.Frontiers in immunology · 2022Review
- Metabolomic Approaches to Investigate the Effect of Metformin: An Overview.International journal of molecular sciences · 2021Review
- Dairy consumption and hepatocellular carcinoma risk.Annals of translational medicine · 2021Review
- Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism.Frontiers in physiology · 2021Review
- Lipid changes in the metabolome of a single case study with maple syrup urine disease (MSUD) after five days of improved diet adherence of controlled branched-chain amino acids (BCAA).Molecular genetics and metabolism reports · 2020Article
- Growth hormone as a rescue treatment in maple syrup urine disease with lessons from pediatric burn literature, case report and brief literature review.Molecular genetics and metabolism reports · 2020Article
- Metabolism.Essays in biochemistry · 2020Review
- Review
- Loss of theDisease models & mechanisms · 2020Article
- Metformin: Targeting the Metabolo-Epigenetic Link in Cancer Biology.Frontiers in oncology · 2020Review
- LAT1 Protein Content Increases Following 12 Weeks of Resistance Exercise Training in Human Skeletal Muscle.Frontiers in nutrition · 2020Article
- Nuclear Magnetic Resonance-Based Metabolomic Analysis of the Anticancer Effect of Metformin Treatment on Cholangiocarcinoma Cells.Frontiers in oncology · 2020Article
- Mice deficient in the mitochondrial branched-chain aminotransferase (BCATm) respond with delayed tumour growth to a challenge with EL-4 lymphoma.British journal of cancer · 2018Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Maple Syrup Urine Disease (MSUD) is an inherited disorder caused by the dysfunction in the branched chain keto-acid dehydrogenase (BCKDH) enzyme. This leads to buildup of branched-chain keto-acids (BCKA) and branched-chain amino acids (BCAA) in body fluids (e.g. keto-isocaproic acid from the BCAA leucine), leading to numerous clinical features including a less understood skeletal muscle dysfunction in patients. KIC is an inhibitor of mitochondrial function at disease relevant concentrations. A murine model of intermediate MSUD (iMSUD) shows significant skeletal muscle dysfunction as by judged decreased muscle fiber diameter. MSUD is an orphan disease with a need for novel drug interventions. Here using a 96-well plate (liquid chromatography- mass spectrometry (LC-MS) based drug-screening platform we show that Metformin, a widely used anti-diabetic drug, reduces levels of KIC in patient-derived fibroblasts by 20-50%. This Metformin-mediated effect was conserved in vivo; Metformin-treatment significantly reduced levels of KIC in the muscle (by 69%) and serum (by 56%) isolated from iMSUD mice, and restored levels of mitochondrial metabolites (e.g. AMP and other TCA). The drug also decreased the expression of mitochondrial branched chain amino transferase (BCAT) which produces KIC in skeletal muscle. This suggests that Metformin can restore skeletal muscle homeostasis in MSUD by decreasing mitochondrial KIC production.
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