Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes
- PMID: 22307324
- PMCID: PMC3287224
- DOI: 10.1172/JCI59701
Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes
Erratum in
- J Clin Invest. 2012 Apr 2;122(4):1584
Abstract
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.
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Comment in
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NPs -- heart hormones that regulate brown fat?J Clin Invest. 2012 Mar;122(3):804-7. doi: 10.1172/JCI62595. Epub 2012 Feb 6. J Clin Invest. 2012. PMID: 22307322 Free PMC article.
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References
-
- Waldman SA, Rapoport RM, Murad F. Atrial natriuretic factor selectively activates particulate guanylate cyclase and elevates cyclic GMP in rat tissues. . J Biol Chem. 1984;259(23):14332–14334. - PubMed
-
- Maack T, et al. Physiological role of silent receptors of atrial natriuretic factor. Science. 1987;238(4827):675–678. - PubMed
-
- Sarzani R, Paci VM, Dessi-Fulgheri P, Espinosa E, Rappelli A. Comparative analysis of atrial natriuretic peptide receptor expression in rat tissues. . J Hypertens Suppl. 1993;11(5):S214–215. - PubMed
-
- Sarzani R, Dessi-Fulgheri P, Paci VM, Espinosa E, Rappelli A. Expression of natriuretic peptide receptors in human adipose and other tissues. J Endocrinol Invest. 1996;19(9):581–585. - PubMed
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