2-oleoylglycerol and Obesity

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).. 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.. 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).. 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.. 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.

Topics: Adult; Cholecystokinin; Dietary Fats; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Glycerides; Humans; Intestinal Mucosa; Male; Obesity; Peptide YY; Triglycerides

After digestion, dietary triacylglycerol stimulates incretin release in humans, mainly through generation of 2-monoacylglycerol, an agonist for the intestinal G protein-coupled receptor 119 (GPR119). Enhanced incretin release may have beneficial metabolic effects. However, dietary fat may promote weight gain and should therefore be restricted in obesity. We designed C4-dietary oil (1,3-di-butyryl-2-oleoyl glycerol) as a 2-oleoyl glycerol (2-OG)-generating fat type, which would stimulate incretin release to the same extent while providing less calories than equimolar amounts of common triglycerides, e.g., olive oil.. We studied the effect over 180 min of (a) 19 g olive oil plus 200 g carrot, (b) 10.7 g C4 dietary oil plus 200 g carrot and (c) 200 g carrot, respectively, on plasma responses of gut and pancreatic hormones in 13 overweight patients with type 2 diabetes (T2D). Theoretically, both oil meals result in formation of 7.7 g 2-OG during digestion.. Both olive oil and C4-dietary oil resulted in greater postprandial (P ≤ 0.01) glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) responses (incremental area under curve (iAUC)): iAUC. C4-dietary oil enhanced secretion of GLP-1 and GIP to almost the same extent as olive oil, in spite of liberation of both 2-OG and oleic acid, which also may stimulate incretin secretion, from olive oil. Thus, C4-dietary oil is more effective as incretin releaser than olive oil per unit of energy and may be useful for dietary intervention.

Topics: Aged; Area Under Curve; Diabetes Mellitus, Type 2; Dietary Fats, Unsaturated; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glycerides; Glycerol; Humans; Incretins; Male; Meals; Middle Aged; Obesity; Oleic Acid; Olive Oil; Overweight; Postprandial Period; Prodrugs; Receptors, G-Protein-Coupled; Single-Blind Method; Triglycerides

Increasing evidence from laboratory and epidemiologic studies indicates that insufficient sleep may be a risk factor for obesity. Sleep curtailment results in stimulation of hunger and food intake that exceeds the energy cost of extended wakefulness, suggesting the involvement of reward mechanisms. The current study tested the hypothesis that sleep restriction is associated with activation of the endocannabinoid (eCB) system, a key component of hedonic pathways involved in modulating appetite and food intake.. In a randomized crossover study comparing 4 nights of normal (8.5 h) versus restricted sleep (4.5 h) in healthy young adults, we examined the 24-h profiles of circulating concentrations of the endocannabinoid 2-arachidonoylglycerol (2-AG) and its structural analog 2-oleoylglycerol (2-OG). We concomitantly assessed hunger, appetite, and food intake under controlled conditions.. A robust daily variation of 2-AG concentrations with a nadir around the middle of the sleep/overnight fast, followed by a continuous increase culminating in the early afternoon, was evident under both sleep conditions but sleep restriction resulted in an amplification of this rhythm with delayed and extended maximum values. Concentrations of 2-OG followed a similar pattern, but with a lesser amplitude. When sleep deprived, participants reported increases in hunger and appetite concomitant with the afternoon elevation of 2-AG concentrations, and were less able to inhibit intake of palatable snacks.. Our findings suggest that activation of the eCB system may be involved in excessive food intake in a state of sleep debt and contribute to the increased risk of obesity associated with insufficient sleep.. A commentary on this article appears in this issue on page 495.

Topics: Adolescent; Adult; Appetite Regulation; Arachidonic Acids; Circadian Rhythm; Cross-Over Studies; Eating; Endocannabinoids; Fasting; Female; Glycerides; Healthy Volunteers; Humans; Hunger; Hyperphagia; Male; Obesity; Reward; Sleep; Sleep Deprivation; Wakefulness; Young Adult