Weight gain reveals dramatic increases in skeletal muscle extracellular matrix remodeling

Area of Science:

• Human physiology
• Metabolic research
• Obesity studies

Background:

• Obesity is linked to chronic inflammation and adipose tissue extracellular matrix (ECM) remodeling, causing insulin resistance in animal models.
• The relevance of this pathophysiology in humans remains unclear.

Purpose of the Study:

• To investigate if a 10% weight gain from overfeeding induces ECM remodeling in human skeletal muscle and subcutaneous adipose tissue.
• To determine if ECM remodeling is associated with impaired metabolic response, assessed via hyperinsulinemic-euglycemic clamp.

Main Methods:

• Twenty-nine males underwent 8 weeks of overfeeding (40% above baseline energy requirements).
• Assessed gene expression, protein, and histology of ECM and inflammation markers.
• Utilized hyperinsulinemic-euglycemic clamp to measure insulin sensitivity.

Main Results:

• A 10% body weight gain significantly upregulated ECM remodeling genes in skeletal muscle and, to a lesser extent, adipose tissue.
• Increased muscle ECM gene expression correlated with lean tissue gain.
• No changes in adipose tissue or systemic inflammation were observed, but skeletal muscle showed a slight increase in inflammation despite impaired insulin sensitivity.

Conclusions:

• Skeletal muscle ECM remodeling is a significant feature of the pathological environment associated with excess energy intake and obesity.
• Disruption of skeletal muscle ECM remodeling may contribute to the development of metabolic dysfunction.