TY - JOUR
T1 - Intestinal sensing and handling of dietary lipids in gastric bypass-operated patients and matched controls
AU - Martinussen, Christoffer
AU - Dirksen, Carsten
AU - Bojsen-Møller, Kirstine N
AU - Svane, Maria S
AU - Carlsson, Elin R
AU - Hartmann, Bolette
AU - Clausen, Trine R
AU - Veedfald, Simon
AU - Kristiansen, Viggo B
AU - Rehfeld, Jens F
AU - Hansen, Harald S
AU - Holst, Jens J
AU - Madsbad, Sten
N1 - Copyright © The Author(s) 2019.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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 clinicaltrials.gov as NCT03223389.
AB - 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 clinicaltrials.gov as NCT03223389.
KW - 2-oleoyl glycerol
KW - bariatric surgery
KW - diabetes
KW - dietary lipids
KW - gastric bypass
KW - glucagon-like peptide-1
KW - gut hormones
KW - long-chain fatty acids
KW - obesity
KW - structured triacylglycerol
KW - Gastric Bypass
KW - Humans
KW - Triglycerides/metabolism
KW - Male
KW - Adult
KW - Female
KW - Glucagon-Like Peptide 1/blood
KW - Cholecystokinin/blood
KW - Gastric Inhibitory Polypeptide/blood
KW - Gastrointestinal Hormones/blood
KW - Dietary Fats/metabolism
KW - Intestinal Mucosa/metabolism
KW - Obesity/blood
KW - Glycerides/metabolism
KW - Peptide YY/blood
UR - http://www.scopus.com/inward/record.url?scp=85077665232&partnerID=8YFLogxK
U2 - 10.1093/ajcn/nqz272
DO - 10.1093/ajcn/nqz272
M3 - Journal article
C2 - 31742316
SN - 0002-9165
VL - 111
SP - 28
EP - 41
JO - The American journal of clinical nutrition
JF - The American journal of clinical nutrition
IS - 1
ER -