ZAG promotes exercise performance during endurance exercise by lipid utilization in skeletal muscle

Area of Science:

• Exercise Physiology
• Molecular Biology
• Metabolic Research

Background:

• Endurance exercise relies heavily on lipids for energy in skeletal muscle.
• The specific role of the adipocytokine Zinc-α2-glycoprotein (ZAG) in exercise-induced lipid metabolism is not well understood.

Purpose of the Study:

• To investigate the function of Zinc-α2-glycoprotein (ZAG) in regulating skeletal muscle lipid metabolism and endurance exercise performance.
• To elucidate the molecular mechanisms by which ZAG influences lipid handling and mitochondrial function during physical activity.

Main Methods:

• Utilized ZAG knockout and overexpression mouse models, alongside C2C12 cell cultures.
• Analyzed serum ZAG levels post-exercise.
• Quantified triglyceride levels and gene/protein expression of key lipolysis (ATGL, CPT1b, ACSL1), lipid synthesis (FASN), and mitochondrial factors (UCP2, COX1).

Main Results:

• Serum ZAG levels increased significantly after exercise.
• ZAG knockout mice exhibited reduced exercise performance, elevated skeletal muscle triglyceride levels, and altered expression of lipolysis and lipid synthesis factors.
• ZAG knockout also decreased mitochondrial energy metabolism factors (UCP2, COX1).
• ZAG overexpression reduced triglyceride levels and enhanced lipolysis-related factors (ATGL, CPT1b).

Conclusions:

• Zinc-α2-glycoprotein (ZAG) plays a crucial role in enhancing skeletal muscle lipid metabolism and mitochondrial function during endurance exercise.
• ZAG improves endurance exercise performance by positively regulating lipid metabolism and mitochondrial activity.