Disrupted Citric Acid Metabolism Inhibits Hair Growth

The study investigated the role of citric acid (CA) metabolism in hair growth by examining the effects of the citrate synthase (CS)-CA axis in vivo and in vitro. Subcutaneous injection of CA in mice led to significant hair growth suppression, skin lesions, inflammation, cell apoptosis, and promotion of catagen entry through activation of p-p65 and apoptosis signaling in an NLRP3-dependent manner. In cultured human hair follicles (HFs), CA reduced hair shaft production and accelerated catagen entry by similar pathways. Additionally, CA inhibited dermal papilla cell (DPC) proliferation by inducing apoptosis and cell cycle arrest. Knockdown of CS, which is responsible for CA production, reduced CA levels and reversed the negative effects on hair growth, inflammation, and apoptosis. The findings suggest that the CS-CA axis is a crucial mediator in hair growth and could be a potential therapeutic target.