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Randomized Controlled Trial
. 2019 Nov;21(11):2535-2541.
doi: 10.1111/dom.13839. Epub 2019 Aug 19.

Glucagon-like peptide-2 mobilizes lipids from the intestine by a systemic nitric oxide-independent mechanism

Changting Xiao  1 , Priska Stahel  1 , Cecilia Morgantini  1 , Avital Nahmias  1 , Satya Dash  1 , Gary F Lewis  1
Affiliations
Randomized Controlled Trial

Glucagon-like peptide-2 mobilizes lipids from the intestine by a systemic nitric oxide-independent mechanism

Changting Xiao et al. Diabetes Obes Metab. 2019 Nov.

Abstract

Aim: To test the hypothesis that gut hormone glucagon-like peptide-2 (GLP-2) mobilizes intestinal triglyceride (TG) stores and stimulates chylomicron secretion by a nitric oxide (NO)-dependent mechanism in humans.

Methods: In a randomized, single-blind, cross-over study, 10 healthy male volunteers ingested a high-fat formula followed, 7 hours later, by one of three treatments: NO synthase inhibitor L-NG -monomethyl arginine acetate (L-NMMA) + GLP-2 analogue teduglutide, normal saline + teduglutide, or L-NMMA + placebo. TG in plasma and lipoprotein fractions were measured, along with measurement of blood flow in superior mesenteric and coeliac arteries using Doppler ultrasound in six participants.

Results: Teduglutide rapidly increased mesenteric blood flow and TG concentrations in plasma, in TG-rich lipoproteins, and most robustly in chylomicrons. L-NMMA significantly attenuated teduglutide-induced enhancement of mesenteric blood flow but not TG mobilization and chylomicron secretion.

Conclusions: GLP-2 mobilization of TG stores and stimulation of chylomicron secretion from the small intestine appears to be independent of systemic NO in humans.

Keywords: clinical physiology; dyslipidaemia.

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References

REFERENCES

    1. Abumrad NA, Davidson NO. Role of the gut in lipid homeostasis. Physiol Rev. 2012;92:1061-1085.
    1. Lewis GF, Xiao C, Hegele RA. Hypertriglyceridemia in the genomic era: a new paradigm. Endocr Rev. 2015;36:131-147.
    1. Dash S, Xiao C, Morgantini C, Lewis GF. New insights into the regulation of chylomicron production. Annu Rev Nutr. 2015;35:265-294.
    1. Hussain MM. Intestinal lipid absorption and lipoprotein formation. Curr Opin Lipidol. 2014;25:200-206.
    1. Xiao C, Stahel P, Lewis GF. Regulation of chylomicron secretion: focus on post-assembly mechanisms. Cell Mol Gastroenterol Hepatol. 2019;7:487-501.

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