Aerobic Exercise Regulating Arterial Function by Lactate/GPR81 Signaling Pathway

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Metabolic Health

Background:

• G protein-coupled receptor 81 (GPR81) is a lactate receptor with largely unknown roles in arterial function.
• Obesity and ovariectomy impair arterial health and are linked to atherosclerosis.
• Lactate (LA) is the endogenous ligand for GPR81.

Purpose of the Study:

• To investigate the role of GPR81 in regulating arterial function in a mouse model of impaired arterial health.
• To elucidate the signaling pathway through which exercise improves arterial function in this model.

Main Methods:

• A mouse model was created using high-fat diet (HFD) and ovariectomy (OVX) to induce obesity and impaired arterial function.
• Mice underwent an 8-week aerobic exercise intervention.
• Gpr81 knockout mice were used to confirm the role of GPR81.
• Key molecular markers including lactate, GPR81 expression, p-CREB, and eNOS were assessed.

Main Results:

• OVX and obesity increased arterial stiffness, dyslipidemia, and aortic oxidized low-density lipoprotein (ox-LDL).
• Aerobic exercise reversed these adverse effects, increasing serum lactate and aortic GPR81 expression.
• Exercise also increased phosphorylated cAMP-response element-binding protein 1 (p-CREB) and endothelial nitric oxide synthase (eNOS) expression.
• Exercise failed to improve arterial function in Gpr81 knockout mice.

Conclusions:

• Exercise enhances arterial function in ovariectomized obese mice, potentially via the lactate/GPR81/p-CREB/CREB/eNOS signaling pathway.
• GPR81 is crucial for mediating the beneficial effects of exercise on arterial health.
• This pathway represents a potential therapeutic target for improving cardiovascular function.