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Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in isolated human adipocytes by activating AMPK

Souza, Sandra/C and Chau, Mary/DL and Yang, Qing and Gauthier, Marie-Soleil and Clairmont, Kevin and Wu, Zhidan and Gromada, Jesper and Dole, William (2011) Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in isolated human adipocytes by activating AMPK. Biochemical and Biophysical Research Communications, 410 (3). pp. 398-403. ISSN 0006-291X

Abstract

Atrial natriuretic peptide (ANP) regulates cardiovascular function. ANP has also been shown to regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation. ANP exerts a potent lipolytic effect via cGMP-dependent protein kinase (cGK)-I dependent activation of AMP-activated protein kinase (AMPK). Activation of the ANP/cGK signaling cascade also promotes muscle mitochondrial biogenesis and fat oxidation.
Here we demonstrate that ANP regulates lipid metabolism and oxygen utilization in differentiated human adipocytes by activating the AMPK pathway. ANP treatment increased lipolysis by seven fold and oxygen consumption two fold, which were attenuated by inhibition of AMPK activity. More importantly, ANP-induced lipolysis is mediated by the alpha2 subunit of AMPK as introduction of dominant-negative alpha2 subunit of AMPK attenuated ANP effects on lipolysis. ANP-induced activation of AMPK enhanced mitochondrial oxidative capacity as evidenced by a two fold increase in oxygen consumption and induction of mitochondrial genes, including carnitine palmitoyltransferase 1A (CPT1a) by 1.4-fold, cytochrome C (CytC) by 1.3-fold, and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) by 1.4-fold. Treatment of human adipocytes with fatty acids and tumor necrosis factor alpha (TNFalpha) induced insulin resistance and downregulation of mitochondrial genes, which was restored by ANP treatment. These results show that ANP regulates lipid catabolism and enhances energy dissipation through AMPK activation.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords: Atrial natriuretic peptide (ANP), AMP-activated protein kinase (AMPK), human adipocytes, lipolysis, oxygen consumption
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Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15
URI: https://oak.novartis.com/id/eprint/5044

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