title: The 2-monoacylglycerol moiety of dietary fat appears to be responsible for the fat-induced release of GLP-1 in humans.
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.
  
  
  METHODS
  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.
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Faculty of Health Sciences, and Department of Clinical Physiology and Nuclear Medicine, Glostrup Hospital, Glostrup, Denmark; and.
authors.forename: Mette J
authors.initials: MJ
authors.lastname: Mandøe
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Faculty of Health Sciences, and Department of Clinical Physiology and Nuclear Medicine, Glostrup Hospital, Glostrup, Denmark; and.
authors.forename: Katrine B
authors.initials: KB
authors.lastname: Hansen
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research.
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, Denmark.
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Faculty of Health Sciences, and.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; hsh@sund.ku.dk.
authors.forename: Harald S
authors.initials: HS
authors.lastname: Hansen
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002766:Cholecystokinin / Q000097:blood / Q000378:metabolism; D018592:Cross-Over Studies; D018552:Daucus carota; D004041:Dietary Fats / Q000008:administration & dosage*; D005223:Fats / Q000737:chemistry*; D005746:Gastric Emptying; D005749:Gastric Inhibitory Polypeptide / Q000097:blood* / Q000378:metabolism; D005768:Gastrointestinal Hormones / Q000097:blood / Q000378:metabolism; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism*; D005989:Glycerides / Q000737:chemistry; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D050178:Monoglycerides / Q000008:administration & dosage*; D009496:Neurotensin / Q000097:blood / Q000378:metabolism; D019301:Oleic Acid / Q000737:chemistry; D000069463:Olive Oil / Q000737:chemistry; D019894:Peptide YY / Q000097:blood / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D016037:Single-Blind Method; D014280:Triglycerides / Q000097:blood / Q000737:chemistry; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D004041:Dietary Fats; D005223:Fats; C519854:GPR119 protein, human; D005768:Gastrointestinal Hormones; D005989:Glycerides; D007328:Insulin; D050178:Monoglycerides; D000069463:Olive Oil; D043562:Receptors, G-Protein-Coupled; D014280:Triglycerides; D019894:Peptide YY; D019301:Oleic Acid; D009496:Neurotensin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002766:Cholecystokinin; C505247:2-oleoylglycerol; C005830:tributyrin
keywords: 2-oleoyl glycerol; G protein-coupled receptor 119; glucagon-like peptide 1; oleic acid; structured triacylglycerol