Intramuscular Adipose Tissue Accumulation as a Key Determinant of Muscle Dysfunction in Peripheral Artery Disease

Highlights

• Chronic limb-threatening ischemia (CLTI) is characterized by a distinct adipogenic and fibrotic muscular phenotype compared to mild peripheral artery disease (PAD).
• The accumulation of intramuscular adipose tissue (IMAT) is negatively correlated with muscle strength and work output in both human subjects and murine models.
• Fibroadipogenic progenitor cells (FAPs) are the cellular source of IMAT in ischemic muscle, and their adipogenic potential is regulated by Pparγ signaling.
• Genetic or pharmacological inhibition of IMAT formation significantly improves limb function, offering a potential non-revascularization strategy for PAD patients.

Background