ArticleThe Journal of clinical investigation2022
β3-Adrenergic receptor downregulation leads to adipocyte catecholamine resistance in obesity.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 115 citations in OpenAlex.
- Early-Life Betaine Supplementation Drives Sex-Specific Metabolic Programming in Rats, Affecting FGF21 Signaling and Energy Balance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Adipocyte β3-adrenergic receptor signaling attenuates leptin production but is dispensable for fasting induced leptin suppression.American journal of physiology. Endocrinology and metabolism · 2026Article
- CL-316243 facilitates stable atherosclerotic plaque phenotypes in association with suppression of perivascular adipose tissue ferroptosis via upregulating C/EBPβ.Redox biology · 2026Article
- Alternative Receptor Signaling for the Selective and Multifaceted Regulation of Human Brown Adipocytes.International journal of molecular sciences · 2026Review
- Lim Homeobox 8 Is Essential for Beta Adrenergic Stimulation of Thermogenesis in Human Adipocytes.Cells · 2026Article
- Integrated analysis of insulin resistance reveals metabolic remodeling following diet switch-triggered calorie reduction.Science advances · 2026Article
- Lipolysis in Health and Disease: Pathways, Regulation, and Metabolic Consequences.Current diabetes reports · 2026Review
- Muscle Loss Driven by Extracellular Signal-Regulated Kinase Suppression via β-Adrenergic Activation in High-Normal Catecholamine Status.Endocrinology and metabolism (Seoul, Korea) · 2026Article
- The epigenetic role of ADRB3 DNA methylation in post-bariatric energy expenditure for women with obesity: a longitudinal observational study.Scientific reports · 2026Observational
- Aged Male Mice Remain Glucose Tolerant Despite Increased Energy Storage Efficiency Favoring Diet-Induced Obesity.Aging cell · 2026Article
- GCGR agonism requires GABAergic signaling in the medial basal hypothalamus to promote weight loss in obese mice.Molecular metabolism · 2026Article
- Targeting Inflammation with Dietary ω-3 Polyunsaturated Fatty Acids Improved Lipid Mobilization and Flux in Heat-Stressed Wether Lambs.Metabolites · 2026Article
- Selective β3-adrenoceptor agonist reduces energy intake and elevates GDF15 levels in lean and diet-induced obese mice.Endocrine journal · 2026Article
- Genetic regulation of exosome biogenesis pathway in human adipose and muscle tissue and association with obesity and insulin resistance.International journal of obesity (2005) · 2026Article
- Article
- High blood pressure-targeted management associated with reduced benefits of higher body mass index in elderly patients with septic shock: a post hoc analysis of a multicenter randomized controlled trial.Annals of intensive care · 2026Article
- Thermogenic adipose tissue in older adults with obesity: a narrative review of mechanisms, brown fat resistance, and the translational relevance of exercise and nutrition.Frontiers in nutrition · 2026Review
- Chronic Stress Induces Hepatic Steatosis via Brain-Hepatic Sympathetic Axis Mediated Catecholamine Resistance.International journal of biological sciences · 2026Article
- Thermogenesis is limited by cellular competence.Frontiers in cell and developmental biology · 2026Article
- Peripheral Nerve-Cancer Interactions in the Tumor Microenvironment: A Three-Dimensional Framework Integrating Mechanisms, Modulators, and Therapeutic Strategies.Research (Washington, D.C.) · 2026Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
The dysregulation of energy homeostasis in obesity involves multihormone resistance. Although leptin and insulin resistance have been well characterized, catecholamine resistance remains largely unexplored. Murine β3-adrenergic receptor expression in adipocytes is orders of magnitude higher compared with that of other isoforms. While resistant to classical desensitization pathways, its mRNA (Adrb3) and protein expression are dramatically downregulated after ligand exposure (homologous desensitization). β3-Adrenergic receptor downregulation also occurs after high-fat diet feeding, concurrent with catecholamine resistance and elevated inflammation. This downregulation is recapitulated in vitro by TNF-α treatment (heterologous desensitization). Both homologous and heterologous desensitization of Adrb3 were triggered by induction of the pseudokinase TRIB1 downstream of the EPAC/RAP2A/PI-PLC pathway. TRIB1 in turn degraded the primary transcriptional activator of Adrb3, CEBPα. EPAC/RAP inhibition enhanced catecholamine-stimulated lipolysis and energy expenditure in obese mice. Moreover, adipose tissue expression of genes in this pathway correlated with body weight extremes in a cohort of genetically diverse mice and with BMI in 2 independent cohorts of humans. These data implicate a signaling axis that may explain reduced hormone-stimulated lipolysis in obesity and resistance to therapeutic interventions with β3-adrenergic receptor agonists.
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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.