skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Abstract

Highlights: {yields} Treatment of differentiated human adipocytes with atrial natriuretic peptide (ANP) increased lipolysis and oxygen consumption by activating AMP-activated protein kinase (AMPK). {yields} ANP stimulated lipid mobilization by selective activation of the alpha2 subunit of AMPK and increased energy utilization through activation of both the alpha1 and alpha2 subunits of AMPK. {yields} ANP enhanced adipocyte mitochondrial oxidative capacity as evidenced by induction of oxidative mitochondrial genes and increase in oxygen consumption. {yields} Exposure of human adipocytes to fatty acids and (TNF{alpha}) induced insulin resistance and decreased expression of mitochondrial genes which was restored to normal by ANP. -- Abstract: Atrial natriuretic peptide (ANP) has 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 mediated-stimulation 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 alpha2 subunit of AMPK. ANP treatment increased lipolysis by seven fold and oxygen consumption by two fold, bothmore » of which were attenuated by inhibition of AMPK activity. ANP-induced lipolysis was shown to be 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-1{alpha} (PGC-1{alpha}) by 1.4-fold. Treatment of human adipocytes with fatty acids and tumor necrosis factor {alpha} (TNF{alpha}) induced insulin resistance and down-regulation of mitochondrial genes, which was restored by ANP treatment. These results show that ANP regulates lipid catabolism and enhances energy dissipation through AMPK activation in human adipocytes.« less

Authors:
 [1]; ;  [2];  [3]; ; ;  [2];  [1]
  1. Translational Sciences - Translational Medicine, Novartis Institutes for Biomedical Research, Inc., 220 Massachusetts Avenue, Cambridge, MA 02139 (United States)
  2. Cardiovascular and Metabolism Disease Area, Novartis Institutes for Biomedical Research, Inc., 100 Technology Square, Cambridge, MA 02139 (United States)
  3. Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02140 (United States)
Publication Date:
OSTI Identifier:
22204993
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 410; Journal Issue: 3; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMP; CARBOHYDRATES; CARNITINE; CATABOLISM; FATS; GENES; INHIBITION; INSULIN; LIPIDS; MITOCHONDRIA; MUSCLES; OXIDATION; OXYGEN; PEPTIDES; RECEPTORS

Citation Formats

Souza, Sandra C., Chau, Mary D.L., Yang, Qing, Gauthier, Marie-Soleil, Clairmont, Kevin B., Wu, Zhidan, Gromada, Jesper, and Dole, William P., E-mail: bill.dole@novartis.com. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK. United States: N. p., 2011. Web. doi:10.1016/J.BBRC.2011.05.143.
Souza, Sandra C., Chau, Mary D.L., Yang, Qing, Gauthier, Marie-Soleil, Clairmont, Kevin B., Wu, Zhidan, Gromada, Jesper, & Dole, William P., E-mail: bill.dole@novartis.com. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK. United States. doi:10.1016/J.BBRC.2011.05.143.
Souza, Sandra C., Chau, Mary D.L., Yang, Qing, Gauthier, Marie-Soleil, Clairmont, Kevin B., Wu, Zhidan, Gromada, Jesper, and Dole, William P., E-mail: bill.dole@novartis.com. Fri . "Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK". United States. doi:10.1016/J.BBRC.2011.05.143.
@article{osti_22204993,
title = {Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK},
author = {Souza, Sandra C. and Chau, Mary D.L. and Yang, Qing and Gauthier, Marie-Soleil and Clairmont, Kevin B. and Wu, Zhidan and Gromada, Jesper and Dole, William P., E-mail: bill.dole@novartis.com},
abstractNote = {Highlights: {yields} Treatment of differentiated human adipocytes with atrial natriuretic peptide (ANP) increased lipolysis and oxygen consumption by activating AMP-activated protein kinase (AMPK). {yields} ANP stimulated lipid mobilization by selective activation of the alpha2 subunit of AMPK and increased energy utilization through activation of both the alpha1 and alpha2 subunits of AMPK. {yields} ANP enhanced adipocyte mitochondrial oxidative capacity as evidenced by induction of oxidative mitochondrial genes and increase in oxygen consumption. {yields} Exposure of human adipocytes to fatty acids and (TNF{alpha}) induced insulin resistance and decreased expression of mitochondrial genes which was restored to normal by ANP. -- Abstract: Atrial natriuretic peptide (ANP) has 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 mediated-stimulation 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 alpha2 subunit of AMPK. ANP treatment increased lipolysis by seven fold and oxygen consumption by two fold, both of which were attenuated by inhibition of AMPK activity. ANP-induced lipolysis was shown to be 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-1{alpha} (PGC-1{alpha}) by 1.4-fold. Treatment of human adipocytes with fatty acids and tumor necrosis factor {alpha} (TNF{alpha}) induced insulin resistance and down-regulation of mitochondrial genes, which was restored by ANP treatment. These results show that ANP regulates lipid catabolism and enhances energy dissipation through AMPK activation in human adipocytes.},
doi = {10.1016/J.BBRC.2011.05.143},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 410,
place = {United States},
year = {Fri Jul 08 00:00:00 EDT 2011},
month = {Fri Jul 08 00:00:00 EDT 2011}
}