TY - JOUR
T1 - Glucagon-like peptide-2 regulates release of chylomicrons from the intestine
AU - Dash, Satya
AU - Xiao, Changting
AU - Morgantini, Cecilia
AU - Connelly, Philip W.
AU - Patterson, Bruce W.
AU - Lewis, Gary F.
N1 - Funding Information:
Funding This work was supported by an operating grant from the Canadian Institutes of Health Research (G.F.L.) and a National Institutes of Health grant from the Washington University Nutrition Obesity Research Center ( DK056341 to B.W.P.). Gary Lewis holds the Sun Life Financial Chair in Diabetes and the Drucker Family Chair in Diabetes Research, Satya Dash and Cecilia Morgantini are recipients of postdoctoral fellowship awards from the Banting and Best Diabetes Centre (University of Toronto), and Satya Dash is also the recipient of a Focus on Stroke 12 Fellowship Award from the Heart and Stroke Foundation of Canada.
Publisher Copyright:
© 2014 AGA Institute.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - BACKGROUND & AIMS: 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.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.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.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.
AB - BACKGROUND & AIMS: 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.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.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.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.
KW - Enterocyte
KW - Fatty Acid
KW - Human Trial
KW - Plasma Lipid
UR - http://www.scopus.com/inward/record.url?scp=84913568983&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2014.08.037
DO - 10.1053/j.gastro.2014.08.037
M3 - Article
C2 - 25173752
AN - SCOPUS:84913568983
VL - 147
SP - 1275-1284.e4
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 6
ER -