LOX-mediated Adipose Tissue Stiffening Promotes Weight Rebound

Area of Science:

• Biomedical Engineering
• Obesity Research
• Tissue Mechanics

Background:

• Weight rebound is a significant challenge in long-term obesity management.
• Current understanding primarily focuses on physiological factors, neglecting biomechanical influences.
• The role of adipose tissue stiffening in weight regain is largely unexplored.

Purpose of the Study:

• To investigate the contribution of lysyl oxidase (LOX)-mediated adipose tissue (AT) stiffening to weight rebound.
• To explore the LOX-stiffness axis as a potential therapeutic target for obesity.

Main Methods:

• Clinical analysis correlating obesity, AT stiffness, and LOX levels.
• In vivo studies using a weight rebound mouse model.
• In vitro experiments mimicking high-stiffness microenvironments.
• Pharmacological inhibition of LOX in vivo.

Main Results:

• Obesity correlates with elevated AT stiffness and higher LOX levels.
• AT stiffness increases during obesity, persists after weight loss due to fibrosis, and peaks during weight regain.
• LOX expression mirrors AT stiffness changes.
• In vitro high-stiffness environments promote adipocyte differentiation and lipid accumulation in a LOX-dependent manner.
• LOX inhibition significantly reduced weight rebound in mice.

Conclusions:

• LOX-mediated AT stiffening creates a pro-adipogenic mechanical environment.
• This stiffening contributes to accelerated weight rebound and metabolic deterioration.
• The LOX-stiffness axis represents a promising therapeutic target for preventing weight rebound.