title: Glucagon-like peptide-2 and mouse intestinal adaptation to a high-fat diet.
abstract: Endogenous glucagon-like peptide-2 (GLP2) is a key mediator of refeeding-induced and resection-induced intestinal adaptive growth. This study investigated the potential role of GLP2 in mediating the mucosal responses to a chronic high-fat diet (HFD). In this view, the murine small intestine adaptive response to a HFD was analyzed and a possible involvement of endogenous GLP2 was verified using GLP2 (3-33) as GLP2 receptor (GLP2R) antagonist. In comparison with animals fed a standard diet, mice fed a HFD for 14 weeks exhibited an increase in crypt-villus mean height (duodenum, 27.5±3.0%; jejunum, 36.5±2.9%; P<0.01), in the cell number per villus (duodenum, 28.4±2.2%; jejunum, 32.0±2.9%; P<0.01), and in Ki67-positive cell number per crypt. No change in the percent of caspase-3-positive cell in the villus-crypt was observed. The chronic exposure to a HFD also caused a significant increase in GLP2 plasma levels and in GLP2R intestinal expression. Daily administration of GLP2 (3-33) (30-60  ng) for 4 weeks did not modify the crypt-villus height in control mice. In HFD-fed mice, chronic treatment with GLP2 (3-33) reduced the increase in crypt-villus height and in the cell number per villus through reduction of cell proliferation and increase in apoptosis. This study provides the first experimental evidence for a role of endogenous GLP2 in the intestinal adaptation to HFD in obese mice and for a dysregulation of the GLP2/GLP2R system after a prolonged HFD.
authors: Laboratorio di Fisiologia generale, Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari (STEMBIO), Università di Palermo, 90128 Palermo, Italy.
authors: Sara
authors: S
authors: Baldassano
authors: Antonella
authors: A
authors: Amato
authors: Francesco
authors: F
authors: Cappello
authors: Francesca
authors: F
authors: Rappa
authors: Flavia
authors: F
authors: Mulè
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D000067758:Glucagon-Like Peptide-2 Receptor; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D009765:Obesity / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D019440:Anti-Obesity Agents; D053767:Glucagon-Like Peptide 2; D000067758:Glucagon-Like Peptide-2 Receptor; D019394:Ki-67 Antigen; C498355:Mki67 protein, mouse; D010446:Peptide Fragments; D018027:Receptors, Glucagon; C451520:glucagon-like peptide-2 (3-33)