ArticleMolecular metabolism2016
Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export.
Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers, 1 of them a synthesis that pooled it.
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Who cites it
180 citing papers in PubMed, 1 synthesis or guideline pooled it, 264 citations in OpenAlex.
- Pooled it
- Retatrutide and lipid and metabolite profiles in participants with obesity with or without type 2 diabetes.The Journal of clinical endocrinology and metabolism · 2026Trial
- Metabolic impact of dietary glycine supplementation in individuals with severe obesity.Scientific reports · 2025Trial
- Gut Microbiome and Metabolome Alterations in Overweight or Obese Adult Population after Weight-LossInternational journal of molecular sciences · 2024Trial
- High-throughput mediation analysis of human proteome and metabolome identifies mediators of post-bariatric surgical diabetes control.Nature communications · 2021Trial
- Exercise training improves mitochondrial respiration and is associated with an altered intramuscular phospholipid signature in women with obesity.Diabetologia · 2021Trial
- A Novel Dietary Intervention Reduces Circulatory Branched-Chain Amino Acids by 50%: A Pilot Study of Relevance for Obesity and Diabetes.Nutrients · 2020Trial
- Decreased adipose tissue oxygenation associates with insulin resistance in individuals with obesity.The Journal of clinical investigation · 2020Trial
- An Exploratory Phase IIa Study of the PPAR delta/gamma Agonist T3D-959 Assessing Metabolic and Cognitive Function in Subjects with Mild to Moderate Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2020Trial
- Effect of Progressive Weight Loss on Lactate Metabolism: A Randomized Controlled Trial.Obesity (Silver Spring, Md.) · 2018Trial
- Amino Acid Metabolism in Health and Disease.MedComm · 2026Review
- The hallmarks of protein and amino acid restriction in aging and longevity.Cell press blue · 2026Article
- Loss of TAFAZZIN leads to perturbation of amino acid metabolism and reduction of collagen synthesis.bioRxiv : the preprint server for biology · 2026Article
- Associations of habitual coffee intake with testosterone and cardiometabolic markers: the Northern Finland birth cohort 1966 study.European journal of nutrition · 2026Article
- Branched chain amino acid metabolism and microbiome in adolescents with obesity during weight loss therapy.The Journal of clinical investigation · 2026Observational
- Integrated proteomic and metabolomic analyses implicate redox-metabolic pathways in PTSD-associated multisystem disease and accelerated aging.Nature communications · 2026Article
- Plasma metabolites after 10-weeks of glucose vs fructose-sweetened beverages in subjects with overweight/obesity.Journal of the Endocrine Society · 2026Article
- Time-dependent plasma metabolic shifts and mechanistic insights into systemic consequences of cerebral ischemia in middle-aged patients.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Maternal BCAA overnutrition programs persistent dysglycemia in lean adult offspring.Molecular metabolism · 2026Article
- Branched‑chain amino acid metabolism and bone metabolism: Implications for osteoporosis pathogenesis and therapeutic strategies (Review).International journal of molecular medicine · 2026Review
120 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveA branched-chain amino acid (BCAA)-related metabolic signature is strongly associated with insulin resistance and predictive of incident diabetes and intervention outcomes. To better understand the role that this metabolite cluster plays in obesity-related metabolic dysfunction, we studied the impact of BCAA restriction in a rodent model of obesity in which BCAA metabolism is perturbed in ways that mirror the human condition.
methodsZucker-lean rats (ZLR) and Zucker-fatty rats (ZFR) were fed either a custom control, low fat (LF) diet, or an isonitrogenous, isocaloric LF diet in which all three BCAA (Leu, Ile, Val) were reduced by 45% (LF-RES). We performed comprehensive metabolic and physiologic profiling to characterize the effects of BCAA restriction on energy balance, insulin sensitivity, and glucose, lipid and amino acid metabolism.
resultsLF-fed ZFR had higher levels of circulating BCAA and lower levels of glycine compared to LF-fed ZLR. Feeding ZFR with the LF-RES diet lowered circulating BCAA to levels found in LF-fed ZLR. Activity of the rate limiting enzyme in the BCAA catabolic pathway, branched chain keto acid dehydrogenase (BCKDH), was lower in liver but higher in skeletal muscle of ZFR compared to ZLR and was not responsive to diet in either tissue. BCAA restriction had very little impact on metabolites studied in liver of ZFR where BCAA content was low, and BCKDH activity was suppressed. However, in skeletal muscle of LF-fed ZFR compared to LF-fed ZLR, where BCAA content and BCKDH activity were increased, accumulation of fatty acyl CoAs was completely normalized by dietary BCAA restriction. BCAA restriction also normalized skeletal muscle glycine content and increased urinary acetyl glycine excretion in ZFR. These effects were accompanied by lower RER and improved skeletal muscle insulin sensitivity in LF-RES fed ZFR as measured by hyperinsulinemic-isoglycemic clamp.
conclusionsOur data are consistent with a model wherein elevated circulating BCAA contribute to development of obesity-related insulin resistance by interfering with lipid oxidation in skeletal muscle. BCAA-dependent lowering of the skeletal muscle glycine pool appears to contribute to this effect by slowing acyl-glycine export to the urine.
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