Loss of atrial natriuretic peptide signaling causes insulin resistance, mitochondrial dysfunction, and low endurance capacity - RESTORE
Article Dans Une Revue Science Advances Année : 2024

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

Andre Märtens
Lars Roed Ingerslev
Mohamed Elhadad
Denis Joanisse
Charles Coudray
Annette Peters
Christian Gieger
Michaela Kuhn

Résumé

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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hal-04749593 , version 1 (23-10-2024)

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Deborah Carper, Marlène Lac, Marine Coue, Axel Labour, Andre Märtens, et al.. Loss of atrial natriuretic peptide signaling causes insulin resistance, mitochondrial dysfunction, and low endurance capacity. Science Advances , 2024, 10 (41), 18p. ⟨10.1126/sciadv.adl4374⟩. ⟨hal-04749593⟩
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