Intramuscular adipose tissue: from progenitor to pathology

Area of Science:

• Muscle physiology and pathology
• Cellular and molecular biology
• Translational medicine

Background:

• Intramuscular adipose tissue (IMAT) accumulation is common in skeletal muscle diseases, linked to poor function and metabolic issues.
• A key debate is whether IMAT is a passive marker or an active driver of muscle pathology.
• Existing rodent models often fail to replicate human IMAT pathology, posing translational challenges.

Purpose of the Study:

• To review evidence on IMAT's role in muscle pathology.
• To explore mechanisms of IMAT-induced muscle dysfunction.
• To examine the cellular origins and regulation of IMAT.

Main Methods:

• Literature review synthesizing human and animal study findings.
• Analysis of mechanisms by which IMAT impairs muscle function (physical disruption, paracrine signaling).
• Investigation of fibro/adipogenic progenitors (FAPs) as the cellular source of IMAT and regulatory signaling networks.

Main Results:

• IMAT acts as both a physical impediment and a source of disruptive paracrine signals in muscle.
• Fibro/adipogenic progenitors (FAPs) can differentiate into adipocytes under pathological conditions.
• Dysregulation of signaling pathways controlling FAP fate contributes to IMAT accumulation.

Conclusions:

• Emerging evidence strongly suggests IMAT is an active contributor to muscle decline.
• Future research should focus on identifying molecular "brakes" and "triggers" of FAP fate.
• Developing better preclinical models and standardized IMAT quantification methods are crucial for clinical progress.