High-density lipoprotein maintains skeletal muscle function by modulating cellular respiration in mice

Area of Science:

• Metabolic research
• Mitochondrial bioenergetics
• Cardiovascular disease research

Background:

• Abnormal glucose metabolism and low high-density lipoprotein (HDL) are linked to cardiovascular disease.
• HDL's role in modulating mitochondrial function in skeletal muscle remains unclear.

Purpose of the Study:

• To investigate the impact of HDL levels on skeletal muscle mitochondrial bioenergetics.
• To determine if HDL influences glucose metabolism and endurance capacity.

Main Methods:

• Utilized genetically modified mouse models: apolipoprotein A-I transgenic (apoA-I tg) mice with high HDL and apoA-I-deficient (apoA-I ko) mice with low HDL.
• Assessed glucose metabolism, glucose tolerance, ATP synthesis, and endurance capacity.
• Examined HDL's direct effects on glucose oxidation in C2C12 muscle cells.

Main Results:

• ApoA-I ko mice showed hyperglycemia, impaired glucose tolerance, reduced ATP synthesis, and decreased endurance.
• HDL directly enhanced glucose oxidation, glycolysis, and mitochondrial respiration in muscle cells.
• ApoA-I tg mice displayed improved glucose homeostasis, reduced fat mass, and protected endurance capacity, even preventing high-fat diet-induced metabolic dysfunction.

Conclusions:

• HDL plays a crucial role in maintaining skeletal muscle mitochondrial function and glucose metabolism.
• Findings suggest HDL-raising therapies could offer therapeutic benefits for type 2 diabetes mellitus by improving mitochondrial function beyond cardiovascular protection.