Longevity & AgingBile Acid TCDCA Reverses Obesity-Driven Vascular Damage via a Novel Endothelial Pathway
Researchers assessed vascular function in 213 non-hypertensive obese patients and found significant endothelial dysfunction (ED) that was poorly predicted by traditional cardiovascular risk factors. Serum metabolomics identified chenodeoxycholic acid (CDCA), a bile acid, as inversely correlated with ED severity. Its taurine-conjugated derivative, taurochenodeoxycholic acid (TCDCA), protected against obesity-induced ED and hypertension in multiple models. Mechanistically, TCDCA activates the endothelial receptor FXR, which elevates ATF4 transcription by relieving PHB1-mediated suppression, ultimately boosting serine and one-carbon metabolism to restore endothelial health. These findings establish CDCA as a biomarker and TCDCA as a candidate therapeutic for obesity-related cardiovascular disease.
