ArticleNature metabolism2024
Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Review
- Orai1-mediated CaExperimental & molecular medicine · 2026Article
- Phosphomannomutase 1 restrains adipose thermogenic programming via inosine signaling.Molecular metabolism · 2026Article
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- EctoShed: a novel gene delivery platform for functional analysis of adipocyte-shed proteoforms.BMC research notes · 2026Article
- The exonic SNP rs11676272-C risk allele mediates diet-induced obesity and reduces enhancer activation.EMBO reports · 2026Article
- CircadianiScience · 2026Article
- Acyl-CoA Binding Protein in White and Brown Adipose Tissue Is Dispensable for Systemic Energy Metabolism in Mice.Acta physiologica (Oxford, England) · 2026Article
- The rs713586 risk variant dysregulates ADCY3 rather than DNAJC27, leading to obesity through ZFP42-TET1-mediated DNA methylation.EBioMedicine · 2026Article
- Genetic architecture of obesity and advances in precision pharmacotherapy: a comprehensive review.Acta biochimica Polonica · 2026Review
- Adenylosuccinate Synthase 1 Deficiency Improves Energy Metabolism by Promoting Adipose Tissue Re-esterification via Glycerol Kinase Upregulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Latest Advances in Obesity Treatment by Regulating Adipocyte Thermogenesis.PPAR research · 2026Review
- Transcriptome analysis reveals reduced lipid accumulation and mitochondrial metabolic remodeling in ADCY3-overexpressing adipocytes.Functional & integrative genomics · 2025Article
- Brown adipocytes from pluripotent stem cells: a promising therapy for obesity.Molecular biology reports · 2025Review
- Type 2 Diabetes-Associated Phenylacetylglutamine Induces Deleterious Inflammation Cycle in Myeloid Cells through βAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Chaperone-mediated autophagy controls brown adipose tissue thermogenic activity.Science advances · 2025Article
- Article
- SOX4 facilitates brown fat development and maintenance through EBF2-mediated thermogenic gene program in mice.Cell death and differentiation · 2025Article
- Cold exposure and the cardiovascular system: from physiological adaptation to pathological risk.Frontiers in physiology · 2025Review
- Exploring Genetic Markers for Cold-Heat Patterns: Integrating Traditional Medicine With Modern Genomic Research.Genetics research · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
34 authors.
Funding
Abstract
Promoting brown adipose tissue (BAT) activity innovatively targets obesity and metabolic disease. While thermogenic activation of BAT is well understood, the rheostatic regulation of BAT to avoid excessive energy dissipation remains ill-defined. Here, we demonstrate that adenylyl cyclase 3 (AC3) is key for BAT function. We identified a cold-inducible promoter that generates a 5' truncated AC3 mRNA isoform (Adcy3-at), whose expression is driven by a cold-induced, truncated isoform of PPARGC1A (PPARGC1A-AT). Male mice lacking Adcy3-at display increased energy expenditure and are resistant to obesity and ensuing metabolic imbalances. Mouse and human AC3-AT are retained in the endoplasmic reticulum, unable to translocate to the plasma membrane and lack enzymatic activity. AC3-AT interacts with AC3 and sequesters it in the endoplasmic reticulum, reducing the pool of adenylyl cyclases available for G-protein-mediated cAMP synthesis. Thus, AC3-AT acts as a cold-induced rheostat in BAT, limiting adverse consequences of cAMP activity during chronic BAT activation.
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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 Socratic graph.