Spatiotemporal AMPKα2 deletion in mice induces cardiac dysfunction, fibrosis and cardiolipin remodeling associated with mitochondrial dysfunction in males only

Abstract

Highlights AMPK is a metabolic sensor of cellular energy which regulates energy homeostasis. We generated a cardiac-specific inducible deletion of Ampkα2 and demonstrated that this deletion induces mild cardiac dysfunction in male only. Cardiac dysfunction observed in males was associated with cardiac fibrosis and cardiac cardiolipin remodeling that are not seen in females. Although no significant cardiac function alteration was noticed in ovariectomized female Ampkα2ciKO mice, these latter exhibited cardiac fibrosis and mild cardiolipins remodeling. Our results show a higher dependence on AMPK signaling fibrosis and cardiolipin biosynthesis/maturation in males, either due to the absence of female hormones protection or/and to the action of male hormones. This may contribute to the known difference in cardiovascular risk and outcome between sexes.

Keywords

• Heart
• AMP-activated protein kinase
• Fibrosis
• Cardiolipins
• Energy metabolism