A Gut-Restricted Liver X Receptor Agonist Ameliorates Liver Injury in Experimental Short Bowel Syndrome - PubMed
5 days ago
- #Short Bowel Syndrome
- #Liver X Receptor
- #Intestinal Failure-Associated Liver Disease
- Short bowel syndrome (SBS) results from extensive small intestine removal and is linked to high morbidity, including intestinal failure-associated liver disease (IFALD).
- Systemic liver X receptor (LXR) agonists showed promise in suppressing IFALD in mice but failed in clinical trials due to side effects like hepatic steatosis and hyperlipidemia.
- Researchers developed WUSTL0717, a gut-restricted LXR agonist, to avoid systemic effects while providing liver protection.
- WUSTL0717 activated LXR target genes in the small intestine but not the liver, improving outcomes in a preclinical SBS mouse model.
- Treatment with WUSTL0717 increased portal venous Apolipoprotein A1 (ApoA1) and spared phospholipids, both linked to HDL and liver protection.
- Intestinal ApoA1 deficiency worsened IFALD, while higher portal venous ApoA1 and phospholipids correlated with reduced liver collagen accumulation.
- WUSTL0717 also improved nutrient absorption and promoted body weight recovery in SBS.
- Gut-restricted LXR agonists like WUSTL0717 offer a promising approach to treating SBS-related liver injury without systemic side effects.