ArticleAging cell2024
Chronic β3-AR stimulation activates distinct thermogenic mechanisms in brown and white adipose tissue and improves systemic metabolism in aged mice.
Article in Aging cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Adipose Tissue Browning in MASLD and Its Molecular Mechanisms and Metabolic Crosstalk.Current obesity reports · 2026Review
- Advances in research on thermogenic substances.Journal of physiological anthropology · 2026Review
- Time-restricted feeding improves metabolic flexibility, promotes beiging, and mitigates fibro-inflammation in the adipose tissue of aged mice.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- Review
- 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
- Novel insights into β3-adrenoceptor function in a model of retinopathy of prematurity: the contribution of astrocytes to retinal protection.Frontiers in neuroscience · 2026Article
- Basal metabolic rate as a protective factor against osteoporosis: a multi-cohort longitudinal study from three international aging databases.Frontiers in nutrition · 2026Article
- Chronic Stress Induces Hepatic Steatosis via Brain-Hepatic Sympathetic Axis Mediated Catecholamine Resistance.International journal of biological sciences · 2026Article
- From endocrine to immune: therapeutic potential of brown adipose tissue in remodelling the cardiovascular immune microenvironment.Frontiers in immunology · 2026Review
- TMEM120A maintains adipose tissue lipid homeostasis through ER CoA channeling.Nature communications · 2025Article
- Semaphorin3A Rewires CD4International journal of molecular sciences · 2025Article
- Adipose tissue aging as a risk factor for metabolic organ abnormalities: mechanistic insights and the role of exercise interventions.Lipids in health and disease · 2025Review
- Exposure to predator threat engages sympathetic nervous system outflow to skeletal muscle.Autonomic neuroscience : basic & clinical · 2025Article
- Advancements in Beta-Adrenergic Therapy and Novel Personalised Approach for Portal Hypertension: A Narrative Review.Life (Basel, Switzerland) · 2025Review
- Article
- Ucp1 Ablation Improves Skeletal Muscle Glycolytic Function in Aging Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Chronic β3-AR stimulation activates distinct thermogenic mechanisms in brown and white adipose tissue and improves systemic metabolism in aged mice.Aging cell · 2024Article
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14 authors.
Funding
Abstract
Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle-aged and older populations, which bear the highest obesity prevalence in the United States (approximately 40%), remains uncertain due to age-related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the β3-adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18-month-old) C57BL/6JN mice. Sustained β3-AR treatment resulted in reduced fat mass, increased energy expenditure, increased fatty acid oxidation and mitochondrial activity in adipose depots, improved glucose homeostasis, and a favorable adipokine profile. At the cellular level, CL treatment increased uncoupling protein 1 (UCP1)-dependent thermogenesis in brown adipose tissue (BAT). However, in white adipose tissue (WAT) depots, CL treatment increased glycerol and lipid de novo lipogenesis (DNL) and turnover suggesting the activation of the futile substrate cycle of lipolysis and reesterification in a UCP1-independent manner. Increased lipid turnover was also associated with the simultaneous upregulation of proteins involved in glycerol metabolism, fatty acid oxidation, and reesterification in WAT. Further, a dose-dependent impact of CL treatment on inflammation was observed, particularly in subcutaneous WAT, suggesting a potential mismatch between fatty acid supply and oxidation. These findings indicate that chronic β3-AR stimulation activates distinct cellular mechanisms that increase energy expenditure in BAT and WAT to improve systemic metabolism in aged mice. Considering that people lose BAT with aging, activation of futile lipid cycling in WAT presents a novel strategy for improving age-related metabolic dysfunction.
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