C-type natriuretic peptide is a pivotal regulator of metabolic homeostasis

• DOI: 10.1073/pnas.2116470119
• Publication Date: 2022-03-25T18:14:07Z
• Authors: Cristina Perez-Te...; Aisah A. Aubdool; Raj Makwana; Gareth J. Sanger; Roland H. Stimson; Li F. Chan; Amie J. Moyes; Adrian J. Hobbs
• Keywords: Energy homeostasis; Homeostasis

Thermogenesis and adipogenesis are tightly regulated mechanisms that maintain lipid homeostasis energy balance; dysfunction of these critical processes underpins obesity contributes to cardiometabolic disease. C-type natriuretic peptide (CNP) fulfills a multimodal protective role in the cardiovascular system governing local blood flow, angiogenesis, cardiac function, immune cell reactivity. Herein, we investigated parallel, preservative function for CNP coordinating metabolic homeostasis. Global inducible knockout mice exhibited reduced body weight, higher temperature, lower adiposity, greater expenditure vivo. This thermogenic phenotype was associated with increased expression uncoupling protein-1 preferential utilization by mitochondria, switch corroborated corresponding diminution insulin secretion glucose clearance. Complementary studies isolated murine human adipocytes revealed exerts regulatory actions inhibiting sympathetic programming via Gi-coupled receptor (NPR)-C reducing peroxisome proliferator-activated receptor-γ coactivator-1α expression, while concomitantly driving NPR-B/protein kinase-G. Finally, identified an association between CNP/NPR-C patient samples. These findings establish pivotal physiological as balance Pharmacological targeting receptors may offer therapeutic utility syndrome related disorders.