PT  - JOURNAL ARTICLE
AU  - Brigitte Jia
AU  - Alexander Hasse
AU  - Fubiao Shi
AU  - Sheila Collins
TI  - Exercise performance is not improved in mice with skeletal muscle deletion of natriuretic peptide clearance receptor
AID  - 10.1101/2022.08.30.505918
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.08.30.505918
4099  - http://biorxiv.org/content/early/2022/09/02/2022.08.30.505918.short
4100  - http://biorxiv.org/content/early/2022/09/02/2022.08.30.505918.full
AB  - Natriuretic peptides (NP), including atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), play essential roles in regulating blood pressure, cardiovascular homeostasis, and systemic metabolism. One of the major metabolic effects of NP is manifested by their capacity to stimulate lipolysis and the thermogenesis gene program in adipocytes, however, their metabolic effect on skeletal muscle is much less appreciated. There are three NP receptors (NPR): NPRA, NPRB, and NPRC, and all three NPR genes are expressed in C2C12 myocytes. Treatment with either ANP, BNP, or CNP evokes the cGMP signaling process in C2C12 myocytes. We then generated a genetic model with Nprc gene deletion in skeletal muscle and tested whether enhancing NP signaling by preventing its clearance in skeletal muscle would improve exercise performance in mice. Under sedentary conditions, Nprc skeletal muscle knockout (MKO) mice showed comparable exercise performance to their floxed littermates in terms of maximal running velocity and total endurance running time. Eight weeks of voluntary running-wheel training in a young cohort increased exercise performance, but no significant differences were observed in MKO compared with control mice. Furthermore, 6-weeks of treadmill training in a relatively aged cohort also increased exercise performance compared with their baseline but did not result in an improvement in MKO mice compared with the controls. In summary, our study suggests that NP signaling is potentially important in myocytes but its function in skeletal muscle in vivo needs to be further studied in alternative physiological conditions or with new genetic mouse models.Competing Interest StatementThe authors have declared no competing interest.