Loss of atrial natriuretic peptide signaling causes insulin resistance, mitochondrial dysfunction, and low endurance capacity

Deborah Carper; Marlène Lac; Marine Coue; Axel Labour; Andre Märtens; Jorge Alberto Ayala Banda; Laurène Mazeyrie; Mie Mechta; Lars Roed Ingerslev; Mohamed Elhadad; Justine Vily Petit; Claire Maslo; Laurent Monbrun; Peggy del Carmine; Yannis Sainte-Marie; Virginie Bourlier; Claire Laurens; Gilles Mithieux; Denis Joanisse; Charles Coudray; Christine Feillet-Coudray; Emilie Montastier; Nathalie Viguerie; Geneviève Tavernier; Melanie Waldenberger; Annette Peters; Rui Wang-Sattler; Jerzy Adamski; Karsten Suhre; Christian Gieger; Gabi Kastenmüller; Thomas Illig; Ralf Lichtinghagen; Jochen Seissler; Remy Mounier; Karsten Hiller; Jens Jordan; Romain Barrès; Michaela Kuhn; Dominik Pesta; Cedric Moro

doi:10.1126/sciadv.adl4374

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Loss of atrial natriuretic peptide signaling causes insulin resistance, mitochondrial dysfunction, and low endurance capacity

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Loss of atrial natriuretic peptide signaling causes insulin resistance, mitochondrial dysfunction, and low endurance capacity

Deborah Carper, Marlène Lac, Marine Coue, Axel Labour, Andre Märtens, Jorge Alberto Ayala Banda, Laurène Mazeyrie, Mie Mechta, Lars Roed Ingerslev, Mohamed Elhadad, …

Science Advances , Vol.10(41)

11/10/2024

DOI: https://doi.org/10.1126/sciadv.adl4374

PMID: 39383215

Abstract

animal

endurance

genetics

human

insulin resistance

knockout mouse

male

metabolism

mitochondrion

animal

Type 2 diabetes (T2D) and obesity are strongly associated with low natriuretic peptide (NP) plasma levels and a down-regulation of NP guanylyl cyclase receptor-A (GCA) in skeletal muscle and adipose tissue. However, no study has so far provided evidence for a causal link between atrial NP (ANP)/GCA deficiency and T2D pathogenesis. Here, we show that both systemic and skeletal muscle ANP/GCA deficiencies in mice promote metabolic disturbances and prediabetes. Skeletal muscle insulin resistance is further associated with altered mitochondrial function and impaired endurance running capacity. ANP/GCA-deficient mice exhibit increased proton leak and reduced content of mitochondrial oxidative phosphorylation proteins. We further show that GCA is related to several metabolic traits in T2D and positively correlates with markers of oxidative capacity in human skeletal muscle. Together, these results indicate that ANP/GCA signaling controls muscle mitochondrial integrity and oxidative capacity in vivo and plays a causal role in the development of prediabetes.

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Title: Loss of atrial natriuretic peptide signaling causes insulin resistance, mitochondrial dysfunction, and low endurance capacity
Creators - without role: Deborah Carper - Institut des Maladies Métaboliques et Cardiovasculaires
Marlène Lac - Institut des Maladies Métaboliques et Cardiovasculaires
Marine Coue - Institut des Maladies Métaboliques et Cardiovasculaires
Axel Labour - Institut des Maladies Métaboliques et Cardiovasculaires
Andre Märtens - Physikalisch-Technische Bundesanstalt
Jorge Alberto Ayala Banda - Institut des Maladies Métaboliques et Cardiovasculaires
Laurène Mazeyrie - Institut des Maladies Métaboliques et Cardiovasculaires
Mie Mechta - University of Copenhagen
Lars Roed Ingerslev - Novo Nordisk Foundation
Mohamed Elhadad - Helmholtz Zentrum München
Justine Vily Petit - Nutrition, Diabète et Cerveau
Claire Maslo - Institut des Maladies Métaboliques et Cardiovasculaires
Laurent Monbrun - Université Toulouse III - Paul Sabatier
Peggy del Carmine - Inserm
Yannis Sainte-Marie - Institut des Maladies Métaboliques et Casdiovasculaires
Virginie Bourlier - Université Toulouse III - Paul Sabatier
Claire Laurens - Institut des Maladies Métaboliques et Cardiovasculaires
Gilles Mithieux - Inserm
Denis Joanisse - Université Laval
Charles Coudray - Université de Montpellier, Dynamique du Muscle et Métabolisme - DMEM
Christine Feillet-Coudray - Université de Montpellier, Dynamique du Muscle et Métabolisme - DMEM
Emilie Montastier - Université Toulouse III - Paul Sabatier
Nathalie Viguerie - Institut des Maladies Métaboliques et Cardiovasculaires
Geneviève Tavernier - Institut des Maladies Métaboliques et Cardiovasculaires
Melanie Waldenberger - Helmholtz Zentrum München
Annette Peters - Helmholtz Zentrum München
Rui Wang-Sattler - Helmholtz Zentrum München
Jerzy Adamski - Helmholtz Zentrum München
Karsten Suhre - University of California, Davis
Christian Gieger - Helmholtz Zentrum München
Gabi Kastenmüller - Scripps Research Institute
Thomas Illig - Medizinische Hochschule Hannover
Ralf Lichtinghagen - Medizinische Hochschule Hannover
Jochen Seissler - Ludwig-Maximilians-Universität München
Remy Mounier - Inserm
Karsten Hiller - Physikalisch-Technische Bundesanstalt
Jens Jordan - University of Cologne
Romain Barrès - Novo Nordisk Foundation
Michaela Kuhn - University of Würzburg
Dominik Pesta - University of Cologne
Cedric Moro - Institut des Maladies Métaboliques et Cardiovasculaires
Publication Details: Science Advances , Vol.10(41)
Identifiers: 9939858309311
Academic Unit: Dynamique du Muscle et Métabolisme - DMEM
Language: English
Resource Type: Journal article
Local Fields: hal-04749593