Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Clinical Investigation Année : 2012

Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes.

Marica Bordicchia
  • Fonction : Auteur
Dianxin Liu
  • Fonction : Auteur
Ez-Zoubir Amri
Paolo Dessì-Fulgheri
  • Fonction : Auteur
Chaoying Zhang
  • Fonction : Auteur
Nobuyuki Takahashi
  • Fonction : Auteur
Riccardo Sarzani
  • Fonction : Auteur
Sheila Collins
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-00758279 , version 1 (28-11-2012)

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Citer

Marica Bordicchia, Dianxin Liu, Ez-Zoubir Amri, Gerard Ailhaud, Paolo Dessì-Fulgheri, et al.. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes.. Journal of Clinical Investigation, 2012, 122 (3), pp.1022-36. ⟨10.1172/JCI59701⟩. ⟨hal-00758279⟩
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