ArticleNature communications2021
Brown and beige adipose tissue regulate systemic metabolism through a metabolite interorgan signaling axis.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 3 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.
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.
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Who cites it
96 citing papers in PubMed, 3 syntheses or guidelines pooled it, 160 citations in OpenAlex.
- Thermogenic Differentiation of Human Adipocyte Precursors in Culture: A Systematic Review.Cells · 2025Pooled it
- Enhancing fat graft retention through adipose tissue browning: a systematic review.Stem cell research & therapy · 2025Pooled it
- New Mediators in the Crosstalk between Different Adipose Tissues.International journal of molecular sciences · 2024Pooled it
- Article
- Adipose tissue as a humoral-neuronal hub in metabolic regulation.Nature reviews. Endocrinology · 2026Review
- Sphingosine kinase 2 regulates adipocyte browning and whole-body metabolism.Science advances · 2026Article
- The metabokine β-aminoisobutyric acid mediates exercise performance and skeletal muscle adaptation through a PGC1α-BAIBA-PPARδ axis.Nature communications · 2026Article
- Macrophage-derived itaconate is a negative regulator of adipose tissue thermogenesis.Nature metabolism · 2026Article
- The Serpin Superfamily in Adipose Tissue Remodeling: Molecular Drivers of Immune-Metabolic Crosstalk and Insulin Sensitivity.Biology · 2026Review
- Nitrate-Sialin2 axis couples ER-mitochondrial calcium signaling with fatty acid metabolism to drive white adipose browning.Nature communications · 2026Article
- Induction of adipocyte thermogenic program by Rho-associated coiled-coil containing kinase 2.iScience · 2026Article
- Targeting Adipose Tissue Function Protects Against Heart Failure with Preserved Ejection Fraction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Significance of neuroendocrine systems and the gut-brain axis (GBA) in the regulation of obesity.PeerJ · 2026Review
- Maternal Physical Activity and Its Relationship to the Human Milk Metabolome and Infant Body Composition.The Journal of clinical endocrinology and metabolism · 2025Article
- The Artemisia argyi oil reduces high-fat diet-induced obesity by enhancing thermogenesis in brown adipose tissue.NPJ science of food · 2025Article
- Changes of bone, adipose, and muscle-related body compositions in gastric cancers after gastrectomy using deep learning based automatic segmentation.BMC gastroenterology · 2025Article
- Immunoengineering strategies using nanoparticles for obesity treatment.Nano research · 2025Article
- Weight Loss-Associated Remodeling of Adipose Tissue Immunometabolism.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Article
- From Microbial Switches to Metabolic Sensors: Rewiring the Gut-Brain Kynurenine Circuit.Biomedicines · 2025Review
36 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
20 authors at 3 institutions in 1 country.
Funding
Abstract
Brown and beige adipose tissue are emerging as distinct endocrine organs. These tissues are functionally associated with skeletal muscle, adipose tissue metabolism and systemic energy expenditure, suggesting an interorgan signaling network. Using metabolomics, we identify 3-methyl-2-oxovaleric acid, 5-oxoproline, and β-hydroxyisobutyric acid as small molecule metabokines synthesized in browning adipocytes and secreted via monocarboxylate transporters. 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid induce a brown adipocyte-specific phenotype in white adipocytes and mitochondrial oxidative energy metabolism in skeletal myocytes both in vitro and in vivo. 3-methyl-2-oxovaleric acid and 5-oxoproline signal through cAMP-PKA-p38 MAPK and β-hydroxyisobutyric acid via mTOR. In humans, plasma and adipose tissue 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid concentrations correlate with markers of adipose browning and inversely associate with body mass index. These metabolites reduce adiposity, increase energy expenditure and improve glucose and insulin homeostasis in mouse models of obesity and diabetes. Our findings identify beige adipose-brown adipose-muscle physiological metabokine crosstalk.
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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.