Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes
| Autor: | Marica Bordicchia, Riccardo Sarzani, Ez-Zoubir Amri, Gérard Ailhaud, Paolo Dessì-Fulgheri, Sheila Collins, Nobuyuki Takahashi, Chaoying Zhang, Dianxin Liu |
|---|---|
| Přispěvatelé: | Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA) |
| Rok vydání: | 2012 |
| Předmět: |
Male
MESH: Signal Transduction Adipose tissue White adipose tissue 030204 cardiovascular system & hematology p38 Mitogen-Activated Protein Kinases chemistry.chemical_compound 0302 clinical medicine Adipose Tissue Brown Adipocyte Clinical investigation Brown adipose tissue MESH: Thermogenesis MESH: Animals MESH: Models Genetic Receptor [SDV.BDD]Life Sciences [q-bio]/Development Biology 0303 health sciences 030302 biochemistry & molecular biology MESH: Transcription Factors General Medicine Thermogenin medicine.anatomical_structure Corrigendum MESH: Adipose Tissue Research Article medicine.medical_specialty MESH: Myocardium MESH: Mice Transgenic MESH: Mitochondria p38 mitogen-activated protein kinases MESH: Receptors Adrenergic beta Biology MESH: Phenotype MESH: Adipose Tissue Brown 03 medical and health sciences MESH: Mice Inbred C57BL Internal medicine medicine Animals Humans Lipolysis MESH: Natriuretic Peptides Natriuretic Peptides MESH: Mice MESH: Adipocytes 030304 developmental biology MESH: Humans business.industry Myocardium MESH: Male MESH: p38 Mitogen-Activated Protein Kinases Endocrinology chemistry business Thermogenesis |
| Zdroj: | Journal of Clinical Investigation Journal of Clinical Investigation, American Society for Clinical Investigation, 2012, 122 (3), pp.1022-36. ⟨10.1172/JCI59701⟩ |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci63775 |
| Popis: | International audience; The ability of mammals to resist body fat accumulation is linked to their ability to expand the number and activity of "brown adipocytes" within white fat depots. Activation of β-adrenergic receptors (β-ARs) can induce a functional "brown-like" adipocyte phenotype. As cardiac natriuretic peptides (NPs) and β-AR agonists are similarly potent at stimulating lipolysis in human adipocytes, we investigated whether NPs could induce human and mouse adipocytes to acquire brown adipocyte features, including a capacity for thermogenic energy expenditure mediated by uncoupling protein 1 (UCP1). In human adipocytes, atrial NP (ANP) and ventricular NP (BNP) activated PPARγ coactivator-1α (PGC-1α) and UCP1 expression, induced mitochondriogenesis, and increased uncoupled and total respiration. At low concentrations, ANP and β-AR agonists additively enhanced expression of brown fat and mitochondrial markers in a p38 MAPK-dependent manner. Mice exposed to cold temperatures had increased levels of circulating NPs as well as higher expression of NP signaling receptor and lower expression of the NP clearance receptor (Nprc) in brown adipose tissue (BAT) and white adipose tissue (WAT). NPR-C(-/-) mice had markedly smaller WAT and BAT depots but higher expression of thermogenic genes such as Ucp1. Infusion of BNP into mice robustly increased Ucp1 and Pgc-1α expression in WAT and BAT, with corresponding elevation of respiration and energy expenditure. These results suggest that NPs promote "browning" of white adipocytes to increase energy expenditure, defining the heart as a central regulator of adipose tissue biology. |
| Databáze: | OpenAIRE |
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