Intestinal FXR agonism synergizes with leptin to improve obesity by reducing appetite via secretin.

Intestinal FXR agonists reduce obesity by suppressing appetite through leptin- and secretin-dependent mechanisms in diet-induced and db/db mice.

• Why it matters: Obesity's link to metabolic diseases underscores the need for targeted therapies with fewer side effects; understanding mechanisms can improve drug development.
• What they did: Researchers used intestinal-specific FXR agonists in mouse models, including diet-induced and db/db mice, to investigate their effects on obesity and appetite regulation.
• The result: Intestinal FXR agonists significantly decreased obesity by upregulating secretin expression in a leptin-dependent manner, revealing a mechanism involving histone methylation and DNA methylation at the Sct locus.