TY - JOUR
T1 - Lipid absorption and overall intestinal lymphatic transport are impaired following partial small bowel resection in mice
AU - Onufer, Emily J.
AU - Czepielewski, Rafael S.
AU - Han, Yong Hyun
AU - Courtney, Cathleen M.
AU - Sutton, Stephanie
AU - Sescleifer, Anne
AU - Randolph, Gwendalyn J.
AU - Warner, Brad W.
N1 - Funding Information:
This work was supported by Pediatric Gastroenterology Training Grant NIH T32 DK077653 (EJO), the NIAID Primary Caregiver Award R37 AI049653 20S1 (Randolph, Onufer), the National Institutes of Health R01 DK119147 (GJR and BWW), the Digestive Diseases Research Core Center of the Washington University School of Medicine (NIH #P30DK52574), and the Children’s Surgical Sciences Research Institute of the St. Louis Children’s Hospital. This project was supported by the Washington University Institute of Clinical and Translational Sciences which is, in part, supported by the NIH/National Center for Advancing Translational Sciences (NCATS), CTSA grant #UL1 TR002345. RSC was supported by a fellowship award “FA-2020-01-IBD-1 from the Lawrence C. Pakula, MD IBD Education & Innovation Fund”.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Short bowel syndrome (SBS) is associated with diminished levels of serum fats caused by unknown mechanisms. We have shown that mesenteric lymphatics remodel to a more primitive state one week after small bowel resection (SBR); therefore, this study focuses on the effect of chronic lymphatic remodeling and magnitude of resection on intestinal lipid uptake and transport. C57BL6 and Prox1 creER-Rosa26LSLTdTomato (lymphatic reporter) mice underwent 50% or 75% proximal SBR or sham operations. Functional transport of lipids and fecal fat content was measured and lymphatic vasculature was compared via imaging. There was a significant reduction in functional transport of cholesterol and triglyceride after SBR with increasing loss of bowel, mirrored by a progressive increase in fecal fat content. We also describe significant morphological changes in the lymphatic vasculature in both the lamina propria and mesentery. Intestinal lymphatic drainage assay in vivo demonstrated a marked reduction of systemic absorption after resection. Intestinal lymphatic vessels significantly remodel in the setting of chronic SBS. This remodeling may account at least in part for impaired intestinal uptake and transport of fat via the compromised lymphatic architecture. We believe that these changes may contribute to the development of intestinal failure associated liver disease (IFALD), a major morbidity in patients with SBS.
AB - Short bowel syndrome (SBS) is associated with diminished levels of serum fats caused by unknown mechanisms. We have shown that mesenteric lymphatics remodel to a more primitive state one week after small bowel resection (SBR); therefore, this study focuses on the effect of chronic lymphatic remodeling and magnitude of resection on intestinal lipid uptake and transport. C57BL6 and Prox1 creER-Rosa26LSLTdTomato (lymphatic reporter) mice underwent 50% or 75% proximal SBR or sham operations. Functional transport of lipids and fecal fat content was measured and lymphatic vasculature was compared via imaging. There was a significant reduction in functional transport of cholesterol and triglyceride after SBR with increasing loss of bowel, mirrored by a progressive increase in fecal fat content. We also describe significant morphological changes in the lymphatic vasculature in both the lamina propria and mesentery. Intestinal lymphatic drainage assay in vivo demonstrated a marked reduction of systemic absorption after resection. Intestinal lymphatic vessels significantly remodel in the setting of chronic SBS. This remodeling may account at least in part for impaired intestinal uptake and transport of fat via the compromised lymphatic architecture. We believe that these changes may contribute to the development of intestinal failure associated liver disease (IFALD), a major morbidity in patients with SBS.
UR - http://www.scopus.com/inward/record.url?scp=85133573790&partnerID=8YFLogxK
U2 - 10.1038/s41598-022-15848-6
DO - 10.1038/s41598-022-15848-6
M3 - Article
C2 - 35798817
AN - SCOPUS:85133573790
SN - 2045-2322
VL - 12
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 11527
ER -