The MMP14-caveolin axis and its potential relevance for lipoedema

Area of Science:

• Endocrinology
• Cell Biology
• Pathophysiology

Background:

• Lipoedema is characterized by adipose tissue expansion, predominantly in the proximal extremities.
• The underlying mechanisms driving lipoedema development remain poorly understood.
• Existing knowledge gaps necessitate novel pathophysiological models.

Purpose of the Study:

• To propose a new model for the pathophysiology of lipoedema.
• To elucidate the role of caveolin 1 (CAV1) dysfunction in lipoedema.
• To explain the estrogen dependence and sexual dimorphism observed in lipoedema.

Main Methods:

• This is a Perspective article, presenting a theoretical model.
• The model integrates known molecular pathways involving CAV1, MMP14, estrogen receptors (ERα), and PROX1.
• Analysis of existing literature to support the proposed mechanisms.

Main Results:

• A proposed model where lipoedema originates from CAV1 dysfunction.
• CAV1 dysfunction leads to uncoupled feedback between CAV1, MMP14, and estrogen receptors.
• Reduced CAV1 activity activates ERα and impairs lymphatic regulation via PROX1.

Conclusions:

• The proposed model suggests lipoedema is an estrogen-dependent adipose tissue disorder.
• CAV1 dysfunction, ERα activation, and PROX1 dysregulation explain key lipoedema features.
• This model accounts for adipose hypertrophy, vascular dysfunction, estrogen dependence, sexual dimorphism, and tissue compliance.