Uric acid promotes dietary lipid absorption through microbiome and metabolomic remodeling via a liver-gut endocrine axis.

Uric acid acts as a liver-derived endocrine regulator that promotes obesity by remodeling gut microbiota and enhancing lipid absorption, with a key role for TIP60.

• Why it matters: Understanding whether uric acid is a cause or consequence of obesity is crucial for developing targeted therapies, as current views mainly see it as a biomarker rather than a driver.
• What they did: The study combined human clinical data and animal models to show that uric acid depletes Lactobacillus johnsonii, reducing its metabolite PLA, which normally suppresses PPARα signaling and lipid absorption. It identified TIP60 as a regulator of hepatic uric acid production, with its inhibition lowering uric acid levels and preventing obesity.
• The result: These findings reveal a liver-gut axis driven by uric acid that accelerates obesity, and suggest that targeting TIP60 could serve as a dual therapy for obesity and hyperuricemia.