title: Is OM-3 synergistic with GLP-2 in intestinal failure?
abstract: Glucagon-like peptide-2 (GLP-2) is a known intestinal growth factor that enhances mucosal mass and function in residual small intestine after massive small bowel resection (MSBR). Luminal omega-3 (OM-3) has been shown to have some growth factor properties. It is possible that their mechanisms of action differ. Thus, we hypothesized that administering these two substances together may have a synergistic effect.
  
  
  
  A total of 60 adult female Sprague-Dawley rats underwent 80% MSBR and divided as follows (n = 15/group): Saline (Control) + regular feeds; GLP-2 + regular feeds; Saline + OM-3 enriched feeds; and GLP-2 + OM-3 enriched feeds. Five animals per group were sacrificed at 7, 14, and 28 days. Small intestine mucosa was harvested. DNA and protein content were measured (mucosal mass markers) at all three time points. Galactose and Glycine absorption were measured (functional capacity markers) at 28 days. Statistical analysis was done by ANOVA with post hoc Tukey's HSD test.
  
  
  
  At all three time points, DNA was increased in all treatment groups compared to control (P < 0.05), but GLP-2 + OM-3 group did not have increased DNA content when compared to either treatments alone. At 7 and 14 d, all three treatment groups had increased protein content compared to control (P < 0.05). At 28 d, GLP-2 + OM-3 did not have increased protein content compared to control or individual treatments (P < 1.0). All three treatment groups had increased absorption of galactose and glycine compared to control (P < 0.05) but not each other.
  
  
  
  Individually, GLP-2 and OM-3 are very effective in enhancing the adaptive process by increasing mucosal mass and function, at all three time points. More importantly, clinically, GLP-2 and OM-3 increase substrate absorption in a rat model of intestinal failure. However, the combination is not synergistic.
authors.affiliation: Department of Surgery, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania. Electronic address: a.karmaker@gmail.com.
authors.forename: Avik
authors.initials: A
authors.lastname: Karmaker
authors.affiliation: Department of Surgery, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania.
authors.forename: Caitlyn M
authors.initials: CM
authors.lastname: Costanzo
authors.affiliation: Department of Surgery, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania; Department of Surgery, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Marshall Z
authors.initials: MZ
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology / Q000627:therapeutic use*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012778:Short Bowel Syndrome / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D005765:Gastrointestinal Agents; D053767:Glucagon-Like Peptide 2; D004247:DNA
keywords: Bowel adaptation; Fatty acid; GLP-2; Glucagon-like Peptide-2; Intestinal adaptation; Intestinal failure; MSBR; OM-3; Omega-3; Short gut syndrome