The 2-monoacylglycerol moiety of dietary fat appears to be responsible for the fat-induced release of GLP-1 in humans

Am J Clin Nutr. 2015 Sep;102(3):548-55. doi: 10.3945/ajcn.115.106799. Epub 2015 Jul 15.

Abstract

Background: Dietary triglycerides can, after digestion, stimulate the intestinal release of incretin hormones through activation of G protein-coupled receptor (GPR) 119 by 2-monoacylglycerol and by the activation of fatty acid receptors for long- and short-chain fatty acids. Medium-chain fatty acids do not stimulate the release of intestinal hormones.

Objective: To dissect the mechanism of fat-induced glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) release in humans, we compared the effects of tributyrin (containing short-chain fatty acids; i.e., butyric acid), olive oil [containing long-chain fatty acids; e.g., oleic acid plus 2-oleoyl glycerol (2-OG)], and 1,3-dioctanoyl-2-oleoyl glycerol (C8-dietary oil), which is digested to form medium-chain fatty acids : i.e., octanoic acid : and 2-OG.

Design: In a randomized, single-blinded crossover study, 12 healthy white men [mean age: 24 y; BMI (in kg/m(2)): 22] were given the following 4 meals on 4 different days: 200 g carrots + 6.53 g tributyrin, 200 g carrots + 13.15 g C8-dietary oil, 200 g carrots + 19 g olive oil, or 200 g carrots. All of the lipids totaled 0.0216 mol. Main outcome measures were incremental areas under the curve for total GLP-1, GIP, and cholecystokinin (CCK) in plasma.

Results: C8-dietary oil and olive oil showed the same GLP-1 response [583 ± 101 and 538 ± 71 (pmol/L) × 120 min; P = 0.733], whereas the GIP response was higher for olive oil than for C8-dietary oil [3293 ± 404 and 1674 ± 270 (pmol/L) × 120 min; P = 0.002]. Tributyrin and carrots alone resulted in no increase in any of the measured hormones. Peptide YY (PYY) and neurotensin responses resembled those of GLP-1. Only olive oil stimulated CCK release.

Conclusions: Under our study conditions, 2-OG and GPR119 activation can fully explain the olive oil-induced secretion of GLP-1, PYY, and neurotensin. In contrast, both oleic acid and 2-OG contributed to the GIP response. Dietary butyrate did not stimulate gut hormone secretion. Olive oil-derived oleic acid seems to be fully responsible for olive oil-induced CCK secretion. This trial was registered at clinicaltrials.gov as NCT02264951.

Keywords: 2-oleoyl glycerol; G protein-coupled receptor 119; glucagon-like peptide 1; oleic acid; structured triacylglycerol.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Body Mass Index
  • C-Peptide / blood
  • Cholecystokinin / blood
  • Cholecystokinin / metabolism
  • Cross-Over Studies
  • Daucus carota
  • Dietary Fats / administration & dosage*
  • Fats / chemistry*
  • Gastric Emptying
  • Gastric Inhibitory Polypeptide / blood*
  • Gastric Inhibitory Polypeptide / metabolism
  • Gastrointestinal Hormones / blood
  • Gastrointestinal Hormones / metabolism
  • Glucagon / blood
  • Glucagon-Like Peptide 1 / blood
  • Glucagon-Like Peptide 1 / metabolism*
  • Glycerides / chemistry
  • Humans
  • Insulin / blood
  • Male
  • Monoglycerides / administration & dosage*
  • Neurotensin / blood
  • Neurotensin / metabolism
  • Oleic Acid / chemistry
  • Olive Oil / chemistry
  • Peptide YY / blood
  • Peptide YY / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Single-Blind Method
  • Triglycerides / blood
  • Triglycerides / chemistry
  • Young Adult

Substances

  • Blood Glucose
  • C-Peptide
  • Dietary Fats
  • Fats
  • GPR119 protein, human
  • Gastrointestinal Hormones
  • Glycerides
  • Insulin
  • Monoglycerides
  • Olive Oil
  • Receptors, G-Protein-Coupled
  • Triglycerides
  • Peptide YY
  • Oleic Acid
  • Neurotensin
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • Glucagon
  • Cholecystokinin
  • 2-oleoylglycerol
  • tributyrin

Associated data

  • ClinicalTrials.gov/NCT02264951