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Updated: May 31, 2026
Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
Liver X receptor agonists enhance intestinal repair in neonatal piglets with massive bowel resection
Haixia Feng1, Weipeng Wang2, Wenjie Wu2
1Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
Insights
Liver X receptor (LXR) agonist GW3965 improved gut barrier integrity and mucosal structure in neonatal piglets with short bowel syndrome (SBS). This suggests LXR pathway targeting may enhance intestinal regeneration for conditions like SBS.
Area of Science:
- Gastroenterology and Hepatology
- Developmental Biology
- Molecular Medicine
Background:
- Neonatal short bowel syndrome (SBS) causes intestinal failure, necessitating parenteral nutrition (PN).
- Liver X receptor (LXR) activation influences lipid metabolism and mucosal repair, suggesting a potential therapeutic role.
Purpose of the Study:
- To investigate the effects of LXR agonist GW3965 on early adaptive responses in neonatal piglets with SBS.
- To evaluate GW3965's impact on intestinal regeneration and barrier function.
Main Methods:
- Utilized a neonatal piglet model of SBS (75% jejunoileal resection).
- Administered GW3965 (2 mg/kg/day) intravenously to piglets and assessed outcomes over 7 days.
- Employed in vitro human intestinal organoid models to complement in vivo findings.
Main Results:
- GW3965 significantly increased villus height and crypt depth in the jejunum, ileum, and colon.
- Treated piglets showed improved gut barrier integrity, evidenced by lower serum lipopolysaccharide (LPS) levels and increased tight junction protein expression.
- GW3965 stimulated intestinal epithelial cell proliferation and human intestinal organoid growth.
- Observed altered colonic gene expression, with upregulation of ileal identity markers.
Conclusions:
- LXR agonist GW3965 promotes intestinal regeneration and enhances gut barrier function in a neonatal SBS model.
- Targeting the LXR pathway offers a potential therapeutic strategy for augmenting intestinal repair in SBS.
- Findings support further investigation of LXR agonists for treating intestinal failure.
Abstract:
Neonatal short bowel syndrome (SBS) often leads to intestinal failure and dependence on parenteral nutrition (PN). Given the role of liver X receptor (LXR) activation in lipid metabolism and mucosal repair, this study was designed to examine the effects of LXR agonist GW3965 on early adaptive responses in neonatal piglets with SBS. Seven-day-old Bama mini-piglets underwent 75% jejunoileal resection and were randomized into a control group (n = 6) and a GW3965-treated group (n = 4; 2 mg/kg/day administered via jugular vein). The effects of GW3965 on postresection intestinal responses and key molecular pathways were investigated using a combination of in vivo (piglets) and in vitro (human intestinal organoid) models. Administration of the LXR agonist GW3965 promoted significant improvements in gut barrier integrity and mucosal structure in the total parenteral nutrition-supported small-nowel resection piglet model during the 7-day postoperative period. GW3965 significantly increased villus height in the jejunum and ileum (both P < 0.05) and crypt depth throughout the remnant intestine and colon (all P < 0.05). Consistent with enhanced barrier function, treated piglets exhibited significantly lower serum lipopolysaccharide levels (P < 0.01) and elevated expression of tight junction proteins. GW3965 also promoted intestinal epithelial cell proliferation. Complementary in vitro studies confirmed that GW3965 directly stimulated the growth of human intestinal organoids. Notably, GW3965 altered colonic gene expression, upregulating markers typically associated with ileal identity. These findings suggest that targeting the LXR pathway may hold therapeutic potential for augmenting the intestinal regeneration.
