ReviewMolecular metabolism2021
Insulin action, type 2 diabetes, and branched-chain amino acids: A two-way street.
Review in Molecular metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 papers, 4 of them syntheses that pooled it.
What it found
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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.
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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.
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Who cites it
177 citing papers in PubMed, 4 syntheses or guidelines pooled it, 269 citations in OpenAlex.
- Metabolomics profile in diabetes and blood glucose regulation: a systematic review.Frontiers in nutrition · 2026Pooled it
- Pooled it
- Efficacy of a High-Protein Diet to Lower Glycemic Levels in Type 2 Diabetes Mellitus: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Relationship between gut microbiota and the pathogenesis of gestational diabetes mellitus: a systematic review.Frontiers in cellular and infection microbiology · 2024Pooled it
- The efficacy of Sarcomeal® oral supplementation plus vitamin D3 on muscle parameters, metabolic factors, and quality of life in diabetic sarcopenia: a randomized controlled clinical trial.Aging clinical and experimental research · 2025Trial
- Dietary Strawberries Improve Serum Metabolites of Cardiometabolic Risks in Adults with Features of the Metabolic Syndrome in a Randomized Controlled Crossover Trial.International journal of molecular sciences · 2023Trial
- Does a Higher Protein Diet Promote Satiety and Weight Loss Independent of Carbohydrate Content? An 8-Week Low-Energy Diet (LED) Intervention.Nutrients · 2022Trial
- Branched-chain amino acids and gut microbiota: coregulation and impact on neurological function via the gut-brain axis.Gut microbes · 2026Review
- The Gut Microbiota-Metabolite-Host Axis in Cardiometabolic Diseases: Bridging Bench to Bedside.Cardiovascular drugs and therapy · 2026Review
- GutiMeta · 2026Article
- Article
- Multi-omics identification of amino acid and redox dysregulation in cystic fibrosis-related diabetes.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2026Article
- The emerging role of branched-chain amino acid metabolism in obesity.International journal of obesity (2005) · 2026Review
- Dietary Patterns, Eating Disorder Risk, Emotional Distress, and Amino Acid Intake in Adults Seeking Weight Loss.Nutrients · 2026Article
- Progressive Metabolic Dysregulation from Prediabetes to Diabetes Revealed by Untargeted Metabolomics.International journal of molecular sciences · 2026Article
- The Complex Relation of Branched-Chain Amino Acids and Inflammation in the Obesity and Diabetes Context.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Branched-Chain and Aromatic Amino Acids Mark Early Metabolic Shifts in Adults with Varying Adiposity.International journal of molecular sciences · 2026Article
- Dynamic [Research square · 2026Article
- Article
- Screening of metabolic-related biomarkers linking intervertebral disc degeneration and type 2 diabetes based on comprehensive bioinformatics analysis and machine learning.Biochemistry and biophysics reports · 2026Article
117 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
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundA strong association of obesity and insulin resistance with increased circulating levels of branched-chain and aromatic amino acids and decreased glycine levels has been recognized in human subjects for decades. SCOPE OF REVIEW: More recently, human metabolomics and genetic studies have confirmed and expanded upon these observations, accompanied by a surge in preclinical studies that have identified mechanisms involved in the perturbation of amino acid homeostasis- how these events are connected to dysregulated glucose and lipid metabolism, and how elevations in branched-chain amino acids (BCAA) may participate in the development of insulin resistance, type 2 diabetes (T2D), and other cardiometabolic diseases and conditions. MAJOR
conclusionsIn human cohorts, BCAA and related metabolites are now well established as among the strongest biomarkers of obesity, insulin resistance, T2D, and cardiovascular diseases. Lowering of BCAA and branched-chain ketoacid (BCKA) levels by feeding BCAA-restricted diet or by the activation of the rate-limiting enzyme in BCAA catabolism, branched-chain ketoacid dehydrogenase (BCKDH), in rodent models of obesity have clear salutary effects on glucose and lipid homeostasis, but BCAA restriction has more modest effects in short-term studies in human T2D subjects. Feeding of rats with diets enriched in sucrose or fructose result in the induction of the ChREBP transcription factor in the liver to increase expression of the BCKDH kinase (BDK) and suppress the expression of its phosphatase (PPM1K) resulting in the inactivation of BCKDH and activation of the key lipogenic enzyme ATP-citrate lyase (ACLY). These and other emergent links between BCAA, glucose, and lipid metabolism motivate ongoing studies of possible causal actions of BCAA and related metabolites in the development of cardiometabolic diseases.
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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.