ArticleDiabetes2020
3-Hydroxyisobutyrate, A Strong Marker of Insulin Resistance in Type 2 Diabetes and Obesity That Modulates White and Brown Adipocyte Metabolism.
Article in Diabetes, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Thermogenic Differentiation of Human Adipocyte Precursors in Culture: A Systematic Review.Cells · 2025Pooled it
- Brown adipose tissues mediate the metabolism of branched chain amino acids during the transitioning from hyperthyroidism to euthyroidism (TRIBUTE).Scientific reports · 2022Trial
- Metabolomic profiles are reflective of hypoxia-induced insulin resistance during exercise in healthy young adult males.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Trial
- The emerging role of branched-chain amino acid metabolism in obesity.International journal of obesity (2005) · 2026Review
- Cross-species urinary metabolomics identifies 2-hydroxyisovalerate as a candidate biomarker for mtDNA-based disorders.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Leucine and Valine Improve Pork Tenderness by Driving Myofiber Transition, Optimizing Lipid Profiles and Enhancing Antioxidant Defense.Animals : an open access journal from MDPI · 2026Article
- Suppression of UCP2 alleviates leukemogenesis by enhancing branched-chain amino acids-induced oxidative stress via activating the PI3K/AKT/mTOR signaling pathway.Genes & diseases · 2026Article
- Branched-chain amino acid metabolism and macrophage polarization: potential regulatory nodes and therapeutic targets in diabetes-associated metabolic inflammation.Frontiers in cellular and infection microbiology · 2026Review
- Branched-chain amino acids and sepsis: from pathological mechanisms to clinical interventions.Nutrition & metabolism · 2025Review
- Branched-chain amino acids in muscle growth: mechanisms, physiological functions, and applications.Journal of animal science and biotechnology · 2025Review
- Epidemiological associations between obesity, metabolism and disease risk: are body mass index and waist-hip ratio all you need?International journal of obesity (2005) · 2025Article
- Integrated analysis of proteomics and metabolomics reveals interactions of energy metabolism and reproduction in hypothalamus of chicken during sexual maturation.Journal of endocrinological investigation · 2025Article
- Microbiome and Long COVID-19: Current Evidence and Insights.International journal of molecular sciences · 2025Review
- The cytosolic branched-chain amino transferase 1 (BCAT1/BCATc) inhibitor reduces mitochondrial capacity in a myotube model of insulin resistance.Journal of endocrinological investigation · 2025Article
- A systematic benchmark of integrative strategies for microbiome-metabolome data.Communications biology · 2025Article
- Metabolomics in cardiometabolic diseases: Key biomarkers and therapeutic implications for insulin resistance and diabetes.Journal of internal medicine · 2025Review
- The Effect of Dexamethasone-Mediated Atrophy on Mitochondrial Function and BCAA Metabolism During Insulin Resistance in C2C12 Myotubes.Metabolites · 2025Article
- Metabolic transition from childhood to adulthood based on two decades of biochemical time series in three longitudinal cohorts.International journal of epidemiology · 2025Article
- Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
Abstract
Circulating branched-chain amino acids (BCAAs) associate with insulin resistance and type 2 diabetes. 3-Hydroxyisobutyrate (3-HIB) is a catabolic intermediate of the BCAA valine. In this study, we show that in a cohort of 4,942 men and women, circulating 3-HIB is elevated according to levels of hyperglycemia and established type 2 diabetes. In complementary cohorts with measures of insulin resistance, we found positive correlates for circulating 3-HIB concentrations with HOMA2 of insulin resistance, as well as a transient increase in 3-HIB followed by a marked decrease after bariatric surgery and weight loss. During differentiation, both white and brown adipocytes upregulate BCAA utilization and release increasing amounts of 3-HIB. Knockdown of the 3-HIB-forming enzyme 3-hydroxyisobutyryl-CoA hydrolase decreases release of 3-HIB and lipid accumulation in both cell types. Conversely, addition of 3-HIB to white and brown adipocyte cultures increases fatty acid uptake and modulated insulin-stimulated glucose uptake in a time-dependent manner. Finally, 3-HIB treatment decreases mitochondrial oxygen consumption and generation of reactive oxygen species in white adipocytes, while increasing these measures in brown adipocytes. Our data establish 3-HIB as a novel adipocyte-derived regulator of adipocyte subtype-specific functions strongly linked to obesity, insulin resistance, and type 2 diabetes.
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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.