ArticleProceedings of the National Academy of Sciences of the United States of America2018
cAMP-inducible coactivator CRTC3 attenuates brown adipose tissue thermogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- The brown fat-enriched exosomal miR-206-3p attenuates hepatic lipogenesis by decreasing pentose phosphate pathway.Life metabolism · 2025Article
- The Genomic Basis of the Svalbard Reindeer's Adaptation to an Extreme Arctic Environment.Genome biology and evolution · 2025Article
- The microprotein C16orf74/MICT1 promotes thermogenesis in brown adipose tissue.The EMBO journal · 2025Article
- Regulation of Sleep Amount by CRTC1 via Transcription ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Human miR-1 Stimulates Metabolic and Thermogenic-Related Genes in Adipocytes.International journal of molecular sciences · 2024Article
- Amphiregulin normalizes altered circuit connectivity for social dominance of the CRTC3 knockout mouse.Molecular psychiatry · 2023Article
- Cold-activated brown fat-derived extracellular vesicle-miR-378a-3p stimulates hepatic gluconeogenesis in male mice.Nature communications · 2023Article
- Impaired BCAA catabolism in adipose tissues promotes age-associated metabolic derangement.Nature aging · 2023Article
- Signatures of selection in indigenous Chinese cattle genomes reveal adaptive genes and genetic variations to cold climate.Journal of animal science · 2023Article
- GPSM1 impairs metabolic homeostasis by controlling a pro-inflammatory pathway in macrophages.Nature communications · 2022Article
- PGEThe EMBO journal · 2022Article
- cAMP-Induced Nuclear Condensation of CRTC2 Promotes Transcription Elongation and Cystogenesis in Autosomal Dominant Polycystic Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues.International journal of molecular sciences · 2021Review
- Activation of the adipocyte CREB/CRTC pathway in obesity.Communications biology · 2021Article
- Comprehensive evaluation of the metabolic effects of porcine CRTC3 overexpression on subcutaneous adipocytes with metabolomic and transcriptomic analyses.Journal of animal science and biotechnology · 2021Article
- Genetic and Functional Characterization of Novel Brown-Like Adipocytes Around the Lamprey Brain.Frontiers in cell and developmental biology · 2021Article
- Role of CRTC2 in Metabolic Homeostasis: Key Regulator of Whole-Body Energy Metabolism?Diabetes & metabolism journal · 2020Review
- Article
- Anabolic and Pro-metabolic Functions of CREB-CRTC in Skeletal Muscle: Advantages and Obstacles for Type 2 Diabetes and Cancer Cachexia.Frontiers in endocrinology · 2019Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
In response to cold exposure, placental mammals maintain body temperature by increasing sympathetic nerve activity in brown adipose tissue (BAT). Triggering of β-adrenergic receptors on brown adipocytes stimulates thermogenesis via induction of the cAMP/PKA pathway. Although cAMP response element-binding protein (CREB) and its coactivators-the cAMP-regulated transcriptional coactivators (CRTCs)-mediate transcriptional effects of cAMP in most tissues, other transcription factors such as ATF2 appear critical for induction of thermogenic genes by cAMP in BAT. Brown adipocytes arise from Myf5-positive mesenchymal cells under the control of PRDM16, a coactivator that concurrently represses differentiation along the skeletal muscle lineage. Here, we show that the CREB coactivator CRTC3 is part of an inhibitory feedback pathway that antagonizes PRDM16-dependent differentiation. Mice with a knockout of CRTC3 in BAT (BKO) have increased cold tolerance and reduced adiposity, whereas mice overexpressing constitutively active CRTC3 in adipose tissue are more cold sensitive and have greater fat mass. CRTC3 reduced sympathetic nerve activity in BAT by up-regulating the expression of miR-206, a microRNA that promotes differentiation along the myogenic lineage and that we show here decreases the expression of VEGFA and neurotrophins critical for BAT innervation and vascularization. Sympathetic nerve activity to BAT was enhanced in BKO mice, leading to increases in catecholamine signaling that stimulated energy expenditure. As reexpression of miR-206 in BAT from BKO mice reversed the salutary effects of CRTC3 depletion on cold tolerance, our studies suggest that small-molecule inhibitors against this coactivator may provide therapeutic benefit to overweight individuals.
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