2020-P: ß3-Adrenergic Receptors Regulate Lipolysis and Thermogenesis in Human Brown/Beige Adipocytes
| Autor: | Hannah J. Lea, Kenneth Y. Zhu, Cheryl Cero, Aaron M. Cypess |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Agonist medicine.medical_specialty Fatty acid metabolism medicine.drug_class Chemistry Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Endocrinology Adipogenesis Internal medicine Adipocyte Brown adipose tissue Internal Medicine medicine Lipolysis Receptor Thermogenesis |
| Zdroj: | Diabetes. 69 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | Activation of rodent brown adipose tissue (BAT) via pharmacological stimulation of β3-adrenergic receptors (β3-AR) leads to metabolic benefit, however in humans, the physiological relevance of BAT and β3-AR remain controversial. To investigate the role of the β3-AR in human brown adipocytes, first, we established a human primary supraclavicular adipocyte in vitro model that upon differentiation preserved the physiological properties brown adipose tissue with increased β-ARs, adipogenic, thermogenic and brown/beige markers. Next, we selective silenced β3-AR expression in differentiated primary brown/beige adipocytes using a lipofectamine-based non-viral transfection. 48h of transfection of siRNA targeting ADRB3 (siRNA-ADRB3) resulted in a 90% reduction in ADRB3 mRNA levels, relative to control siRNA-transfected cells (siRNA-Ctrl). siRNA-ADRB3 also reduced genes of fatty acid metabolism, thermogenesis (UCP1, 90% decrease), and mitochondrial mass. Functionally, lower cAMP levels, lipolysis, oxygen consumption rates and higher glycolysis were caused by silencing β3-AR receptor. Immortalized brown adipocyte (hBA’s), from a separate subject, displayed a similar decrease in lipolysis and cellular respiration. Mirabegron, the selective human β3-AR agonist, stimulated BAT lipolysis and thermogenesis, that were lost after knockdown ADRB3. Similarly, selective subtype human β-AR agonists dobutamine (β1-AR agonist) and terbutaline (β2-AR agonist) treatment also increased lipolysis and thermogenesis, that were also attenuated when β3-AR was silenced. Thus, the β3-AR maintains multiple components of the human brown/beige adipocyte lipolytic and thermogenic cellular machinery. These findings indicate that ADRB3 and β3-AR agonists could be used to achieve metabolic benefit in humans. Disclosure C. Cero: None. H.J. Lea: None. K.Y. Zhu: None. A.M. Cypess: None. |
| Databáze: | OpenAIRE |
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