title: Glucagon-like peptide-2 regulates release of chylomicrons from the intestine.
abstract: OBJECTIVE
  The intestine efficiently incorporates and rapidly secretes dietary fat as chylomicrons (lipoprotein particles comprising triglycerides, phospholipids, cholesterol, and proteins) that contain the apolipoprotein isoform apoB-48. The gut can store lipids for many hours after their ingestion, and release them in chylomicrons in response to oral glucose, sham feeding, or unidentified stimuli. The gut hormone glucagon-like peptide-2 (GLP-2) facilitates intestinal absorption of lipids, but its role in chylomicron secretion in human beings is unknown.
  
  
  METHODS
  We performed a randomized, single-blind, cross-over study, with 2 study visits 4 weeks apart, to assess the effects of GLP-2 administration on triglyceride-rich lipoprotein (TRL) apoB-48 in 6 healthy men compared with placebo. Subjects underwent constant intraduodenal feeding, with a pancreatic clamp and primed constant infusion of deuterated leucine. In a separate randomized, single-blind, cross-over validation study, 6 additional healthy men ingested a high-fat meal containing retinyl palmitate and were given either GLP-2 or placebo 7 hours later with measurement of TRL triglyceride, TRL retinyl palmitate, and TRL apoB-48 levels.
  
  
  RESULTS
  GLP-2 administration resulted in a rapid (within 30 minutes) and transient increase in the concentration of TRL apoB-48, compared with placebo (P = .03). Mathematic modeling of stable isotope enrichment and the mass of the TRL apoB-48 suggested that the increase resulted from the release of stored, presynthesized apoB-48 from the gut. In the validation study, administration of GLP-2 at 7 hours after the meal, in the absence of additional food intake, robustly increased levels of TRL triglycerides (P = .007), TRL retinyl palmitate (P = .002), and TRL apoB-48 (P = .04) compared with placebo.
  
  
  CONCLUSIONS
  Administration of GLP-2 to men causes the release of chylomicrons that comprise previously synthesized and stored apoB-48 and lipids. This transiently increases TRL apoB-48 levels compared with placebo. Clinical trials number at www.clinicaltrials.gov: NCT 01958775.
authors.affiliation: Department of Medicine, Department of Physiology, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada; Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Satya
authors.initials: S
authors.lastname: Dash
authors.affiliation: Department of Medicine, Department of Physiology, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada; Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Changting
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Department of Medicine, Department of Physiology, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada; Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgantini
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Connelly
authors.affiliation: Center for Human Nutrition, Department of Internal Medicine, Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Patterson
authors.affiliation: Department of Medicine, Department of Physiology, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada; Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: gary.lewis@uhn.ca.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Lewis
mesh_terms: D000328:Adult; D053299:Apolipoprotein B-100 / Q000097:blood; D053283:Apolipoprotein B-48 / Q000097:blood; D002914:Chylomicrons / Q000187:drug effects* / Q000378:metabolism; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000008:administration & dosage / Q000493:pharmacokinetics; D004224:Diterpenes; D050171:Dyslipidemias / Q000188:drug therapy* / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000097:blood; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage* / Q000097:blood; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D000084562:Retinyl Esters; D016037:Single-Blind Method; D014280:Triglycerides / Q000097:blood; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D002914:Chylomicrons; D004041:Dietary Fats; D004224:Diterpenes; D005765:Gastrointestinal Agents; D053767:Glucagon-Like Peptide 2; D000084562:Retinyl Esters; D014280:Triglycerides; D014801:Vitamin A; C014794:retinol palmitate; D005947:Glucose
keywords: Enterocyte; Fatty Acid; Human Trial; Plasma Lipid