Deuterated Polyunsaturated Fatty Acids Alleviate In Vitro Skeletal Muscle Dysfunction Induced by Oxidative Stress

Area of Science:

• Biochemistry
• Cell Biology
• Muscle Physiology

Background:

• Oxidative stress causes lipid peroxidation, contributing to skeletal muscle atrophy in diseases.
• Polyunsaturated fatty acids (PUFAs) are vital for muscle cell membranes but prone to peroxidation.
• Current therapies for muscle wasting due to lipid peroxidation are limited.

Purpose of the Study:

• To investigate if deuterated PUFAs (D-PUFAs) can protect muscle cells from oxidative stress.
• To evaluate the potential of D-PUFAs in preventing muscle cell dysfunction and atrophy.

Main Methods:

• Cultured myotubes were treated with native (H-) and deuterated (D-) forms of long-chain PUFAs (arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid).
• Cells were exposed to reactive oxygen species (ROS) or the ferroptosis inducer erastin.
• Lipid peroxidation levels, myotube growth, and expression of antioxidant enzymes were assessed.

Main Results:

• D-PUFAs, unlike H-PUFAs, protected myotubes against ROS-induced lipid peroxidation and dysfunction.
• D-PUFAs also protected against erastin-induced ferroptosis and preserved myogenic differentiation.
• D-PUFAs modulated the expression of endogenous antioxidant enzymes and muscle-specific protein ligases.

Conclusions:

• Deuteration of PUFAs limits their susceptibility to lipid peroxidation.
• D-PUFAs show promise as a novel therapeutic approach to combat oxidative stress-induced skeletal muscle atrophy.
• This strategy could offer new treatments for various musculoskeletal diseases characterized by muscle wasting.