Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability

Area of Science:

• Cell Biology
• Biophysics
• Physiology

Background:

• Adipocyte expansion is vital for energy storage but can lead to metabolic disorders like obesity and lipodystrophy.
• The biomechanical properties of adipocytes, particularly their membrane dynamics during expansion, are poorly understood in relation to these conditions.

Purpose of the Study:

• To investigate the role of adipocyte plasma membrane biomechanics and caveolae in lipid droplet expansion and adipose tissue function.
• To elucidate the molecular mechanisms underlying adipocyte mechanoadaptation during lipid accumulation.

Main Methods:

• In vivo studies using male mice.
• Analysis of adipocyte plasma membrane caveolar domain reorganization during lipid droplet expansion.
• Assessment of adipose tissue stiffness and deformability in wild-type and caveolae-null models.
• Investigating the role of Cav1 Tyr14 phosphorylation using mutagenesis (Tyr14Phe mutation).

Main Results:

• Adipocyte lipid droplet expansion triggers caveolae disassembly, releasing membrane and increasing cell surface area.
• Caveolae-deficient adipose tissue exhibits increased stiffness and reduced deformability, making it prone to rupture.
• Phosphorylation of Cav1 at Tyr14 is essential for caveolae disassembly and proper transfer of proteins (Cav1, EHD2) to the lipid droplet surface.
• A Cav1 Tyr14Phe mutation results in stiffer, smaller adipocytes, reduced adiposity, and impaired mechanoadaptation.

Conclusions:

• Caveolar domain reorganization and disassembly are critical for adipocyte expansion and maintaining adipose tissue mechanical integrity.
• Cav1 phosphoregulation at Tyr14 is a key mechanism controlling caveolae dynamics and adipocyte mechanoadaptation.
• These findings highlight the importance of adipocyte biomechanics in metabolic health and disease.