| First Author | Tian C | Year | 2026 |
| Journal | Cell Host Microbe | Volume | 34 |
| Issue | 8 | Pages | 1646-1662.e11 |
| PubMed ID | 42235504 | Mgi Jnum | J:387148 |
| Mgi Id | MGI:8350916 | Doi | 10.1016/j.chom.2026.05.005 |
| Citation | Tian C, et al. (2026) Uric acid promotes dietary lipid absorption through microbiome and metabolomic remodeling via a liver-gut endocrine axis. Cell Host Microbe |
| abstractText | Hyperuricemia closely correlates with obesity, yet high uric acid (UA) is largely viewed as a consequence or biomarker of obesity rather than a causal driver. Integrating human clinical analyses with animal studies, we redefine UA as a liver-derived endocrine regulator that drives obesity by modulating gut ecology. UA remodels the gut microbiota, selectively depleting Lactobacillus johnsonii by disrupting peptidoglycan synthesis. This depletion reduces microbial phenyllactic acid (PLA)-a metabolite produced by L. johnsonii lactate dehydrogenase that we identify as an endogenous suppressor of intestinal peroxisome proliferator-activated receptor alpha (PPARalpha) signaling. Consequently, PPARalpha disinhibition upregulates fatty acid transporters, accelerating lipid absorption and promoting obesity. Leveraging human genetic data, we pinpoint lysine acetyltransferase 5 (TIP60) as a master regulator of hepatic UA production. Hepatic TIP60 ablation lowers UA, restoring the L. johnsonii-PLA axis and conferring obesity resistance. These findings establish a UA-driven liver-gut axis and nominate TIP60 inhibition as a dual-target therapy for obesity and hyperuricemia. |
