The Mechanobiology of Adipocyte Hypertrophy: Cytoskeletal Remodelling as a Driver of Insulin Resistance in Obesity.

Adipocyte hypertrophy poses an important mechanical challenge-adipocytes can increase in volume up to a thousand-fold while still maintaining their structural integrity. Although lipid metabolism is well studied, little is known about the cytoskeletal adaptations that are required to accommodate this expansion and the resulting pathological consequences. This review critically examines how the cytoskeletal remodelling is associated with insulin resistance. We explore how mechanotransduction pathways like YAP/TAZ, which inhibit the expression of adipogenic genes, are triggered when cortical actin transforms into stress fibres. This review also discusses the role of the microtubule network in lipid droplet fusion and the vimentin cage that regulates lipolysis. Further, we highlight the emerging role of the Septin family (SEPT), specifically the conflicting pro- and anti-adipogenic roles of SEPT7, where SEPTs might act as a molecular brake on adipocyte expansion. We conclude that obesity-induced insulin resistance is partially due to a failure of cytoskeletal mechanics, making cytoskeletal regulators potential therapeutic targets for metabolic disease.