FXR adapts hepatic mitochondrial function to increased substrate oxidation in patients with obesity.

Metabolic pressure shifts signaling pathways of nuclear receptors, including the bile acid receptor FXR, which are sensitive to nutritional inputs. We performed an FXR ChIP-seq-centered multiomic analysis of liver biopsy samples from individuals with or without obesity, who were treated with either placebo or the FXR agonist obeticholic acid, to define metabolic adaptions of FXR signaling pathways. FXR occupied substantially more DNA binding sites in individuals with obesity, and FXR activation by OCA robustly changed the transcriptional output.