A Microphysiological Interface of Skeletal Myobundles and Inflamed Adipose Tissue for Recapitulating Muscle...

Area of Science:

• Biomedical Engineering
• Cell Biology
• Physiology

Background:

• Obesity causes systemic inflammation, negatively impacting skeletal muscle function via adipose tissue signaling.
• Existing models lack the physiological relevance to study adipose-muscle crosstalk in obesity-associated dysfunction.

Purpose of the Study:

• To develop a human cell-based microphysiological system to model obesity-associated skeletal muscle dysfunction.
• To investigate the effects of inflamed adipose tissue on skeletal muscle contractility and metabolism.

Main Methods:

• Engineered muscle tissue (EMT) from human myoblasts formed 3D contractile myobundles.
• Inflamed adipose-macrophage co-culture (IAMC) recapitulated the obese inflammatory microenvironment.
• EMT-IAMC co-cultures were used to assess muscle function and molecular changes.

Main Results:

• Co-culture significantly reduced skeletal muscle contractility.
• Elevated pro-inflammatory mediators were detected.
• Transcriptomic analysis revealed metabolic reprogramming in muscle, including insulin resistance markers.

Conclusions:

• Inflamed adipose tissue detrimentally affects skeletal muscle function.
• The developed platform is valuable for studying adipose-muscle interactions and screening therapies for obesity-related muscle dysfunction.