Deleting adipose FXR exacerbates metabolic defects and induces endocannabinoid lipid, 2-oleoyl glycerol, in obesity.

ABSTRACT: The nutrient sensor farnesoid X receptor (FXR) transcriptionally regulates whole-body lipid and glucose homeostasis. Several studies examined targeting FXR as a modality to treat obesity with varying conflicting results, emphasizing the need to study tissue-specific roles of FXR. We show that deletion of adipocyte Fxr results in increased adipocyte hypertrophy and suppression of several metabolic genes that is akin to some of the changes noted in high-fat diet (HFD)-fed control mice. Moreover, upon HFD challenge, these effects are worsened in adipocyte-specific Fxr knockout mice. We uncover that FXR regulates fatty acid amide hydrolase (Faah) such that its deletion lowers Faah expression. Conversely, FXR activation by its ligand, chenodeoxycholic acid, induces Faah transcription. Notably,

SUBMITTER: Zhou W 

PROVIDER: S-EPMC11946508 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature