Intestinal sensing and handling of dietary lipids in gastric bypass-operated patients and matched controls

Am J Clin Nutr. 2020 Jan 1;111(1):28-41. doi: 10.1093/ajcn/nqz272.


Background: Altered meal-related gut hormone secretion seems important for weight loss and diabetes remission after Roux-en-Y gastric bypass (RYGB). Elucidating the responsible meal components and receptors could aid discovery of new treatments of obesity and diabetes. Enteroendocrine cells respond to digestion products of dietary triacylglycerol, especially long-chain fatty acids (LCFAs) and 2-oleoyl-glycerol (2-OG), but not medium-chain fatty acids (MCFAs).

Objective: We examined the impact of olive oil (20 mL) and its derivates, LCFAs and 2-OG, on enteroendocrine secretions [glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), peptide YY (PYY), and neurotensin (NT)] and on glucose, lipid, and bile acid metabolism in RYGB-operated and unoperated individuals.

Methods: In an exploratory randomized crossover design, 10 RYGB-operated patients and 10 matched controls ingested 3 equimolar triacylglycerol formulations on separate days: olive oil (digested to 2-OG + LCFAs), C8-dietary oil (2-OG + MCFAs), and tricaprylin (MCFAs; negative control). Hormone responses were calculated as area under the curve (AUC).

Results: Independent of group status, olive oil had greater effects than C8-dietary oil on AUCs of plasma GLP-1 (+32%; 95% CI: 23%, 43%; P < 0.01), CCK (+53%, P < 0.01), and NT (+71%, P < 0.01), whereas the effect on GIP differed between groups (+90% in controls, P < 0.01; +24% in RYGB, P = 0.10). Independent of group status, C8-dietary oil had greater effects than tricaprylin on AUCs of plasma CCK (+40%, P < 0.01) and NT (+32%, P < 0.01), but not GLP-1 (+5%; 95% CI: -2.9%, 13%; P = 0.22), whereas the effect on GIP again differed between groups (+78% in controls, P < 0.01; +39% in RYGB, P = 0.01). Distal (GLP-1/PYY/NT), but not proximal (CCK/GIP), enteroendocrine responses were generally greater in RYGB patients than in controls.

Conclusions: The combination of LCFAs plus 2-OG was substantially more effective than 2-OG plus MCFAs in stimulating enteroendocrine secretion in RYGB-operated and matched control individuals. Distal lipid-induced gut hormone release was greater after RYGB.This trial was registered at as NCT03223389.

Keywords: 2-oleoyl glycerol; bariatric surgery; diabetes; dietary lipids; gastric bypass; glucagon-like peptide-1; gut hormones; long-chain fatty acids; obesity; structured triacylglycerol.

Publication types

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

MeSH terms

  • Adult
  • Cholecystokinin / blood
  • Dietary Fats / metabolism*
  • Female
  • Gastric Bypass
  • Gastric Inhibitory Polypeptide / blood
  • Gastrointestinal Hormones / blood
  • Glucagon-Like Peptide 1 / blood
  • Glycerides / metabolism
  • Humans
  • Intestinal Mucosa / metabolism*
  • Male
  • Obesity / blood
  • Obesity / metabolism
  • Obesity / surgery*
  • Peptide YY / blood
  • Triglycerides / metabolism


  • Dietary Fats
  • Gastrointestinal Hormones
  • Glycerides
  • Triglycerides
  • Peptide YY
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • Cholecystokinin
  • 2-oleoylglycerol

Associated data