Gastrointestinal hormones and gastric emptying 20 years after jejunoileal bypass for massive obesity

The gastrointestinal (GI) tract, the key interface between ingested nutrients and the body, plays a critical role in regulating energy homeostasis. Gut-derived signals convey information regarding incoming nutrients to the brain, initiating changes in eating behavior and energy expenditure, to maintain energy balance. Here we review hormonal, neural and nutrient signals emanating from the GI tract and evidence for their role in controlling feeding behavior. Mechanistic studies that have utilized pharmacological and/or transgenic approaches targeting an individual hormone/mediator have yielded somewhat disappointing bodyweight changes, often leading to the hormone/mediator in question being dismissed as a potential obesity therapy. However, the recent finding of sustained weight-reduction in response to systemic administration of a long-acting analog of the gut-hormone glucagon-like peptide-1 (GLP-1) highlights the therapeutic potential of gut-derived signals acting via non-physiological mechanisms. Thus, we also review therapeutics strategies being utilized or developed to leverage GI signals in order to treat obesity.

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“…In addition, circulating NT concentrations are increased following bariatric procedures that increase EEC exposure to nutrients 51 .…”

Section: Neurotensin (Nt)mentioning

confidence: 99%

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

Monteiro

Batterham

2017

Gastroenterology

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“…Vertical banded gastroplasty increases post-meal cholecystokinin plasma levels, 8 whereas Roux-en-Y gastric by-pass inhibits basal and post-prandial ghrelin plasma levels 9 and increases peptideYY (PYY) concentrations. 10 Jejuno-ileal by-pass increases cholecystokinin, motilin, glucagon-like peptide 1 and PYY, 11 delays gastric emptying and reduces hunger sensations. As cholecystokinin, ghrelin and PYY also influence gastrointestinal motility, it can be hypothesized that reduction of gastric emptying could contribute to the satiety effect of the operations.…”

Section: Introductionmentioning

confidence: 99%

Treatment of morbid obesity by intraparietogastric administration of botulinum toxin: a randomized, double-blind, controlled study

et al. 2006

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Objective: The stomach is the main target organ for bariatric surgery, but no medical treatment has been developed to increase satiety and decrease food intake via gastric pathways. The aim of our study was to investigate whether or not the intraparietogastric administration of botulinum toxin A (BTX), able to modify the motility patterns of the stomach, could be useful for treatment of obesity. Design: Double blind controlled study. Subjects: Twenty-four morbidly obese patients (mean weight (s.e.m.) 116.174.89 kg, mean body mass index (BMI) 43.671.09 kg/m 2 ) were blindly randomized to receive 200 IU BTX or placebo into the antrum and fundus of the stomach by intraparietal endoscopic administration. Measurements: We evaluated weight loss, BMI changes, satiety score, the maximal gastric capacity for liquids and the gastric emptying time (octanoic acid breath test). Results: The two groups were homogeneous for anthropometric characteristics. Eight weeks after treatment, BTX patients had significantly higher weight loss (1171.09 vs 5.771.1 kg, Po0.001) and BMI reduction (470.36 vs 270.58 kg/m 2 , Po0.001) and a higher satiety score on a visual analogic scale (7.6370.38 vs 4.7270.44, Po0.001) than controls. Furthermore, BTX patients showed a significantly greater reduction in maximal gastric capacity for liquids (266.6748 vs 139731, Po0.001) and a greater prolongation in gastric emptying time ( þ 18.9378 vs À2.276.9 min, Po0.05). No significant side effects or neurophysiologic changes were found. Conclusions: Topical intragastric BTX was effective in reducing food intake and body weight in morbidly obese patients.

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“…1,8 A downregulation of intestinal nutrient responsive mechanisms and CCK receptors has been reported as well. 9 Also, changes in gastric emptying induced by weight loss, 2,4,11,12 anorectic drugs [19][20][21][22] or bariatric surgery [23][24][25][26] have been observed. The initial faster solid emptying reverted towards normal-weight values after weight loss or remained unchanged.…”

mentioning

confidence: 99%

Influences of fat restriction and lipase inhibition on gastric emptying in obesity

2006

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Objective: Accelerated gastric emptying of solids may play a role in the pathogenesis of obesity. Orlistat, a potent lipase inhibitor, induces fat malabsorption and body weight loss but might accelerate gastric emptying as a result of suppressed CCK release. The aim was to investigate the role of fat restriction and lipase inhibition in CCK release and gastric emptying. Subjects: A total of 28 patients (three male (M)/25 female (F); mean (s.d.) BMI 37.4(3.9) kg/m 2 ) entering a randomized, double-blind, placebo-controlled study. Measurements: CCK release and gastric emptying by scintigraphy at the start (T0), after 1 month of an energy-and fatrestricted diet and placebo (T1), and after 1 month (T2) and 1 year (T3) of randomization to placebo or 120 mg orlistat three times a day. Results: One month of dieting and a weight loss of 2.3 kg (2.1% of initial weight) did not affect gastric emptying of liquids and solids. Basal and meal-stimulated CCK levels remained unaltered. Placebo-treated subjects who continued the diet for 1 month demonstrated a borderline significant suppressed CCK secretion and a weight loss of 1.2 kg (1.0%) without an effect on gastric emptying. After 1 year, the CCK secretion recovered to or beyond values at the start. A significantly slower emptying of solids (17.6 (T3) versus 25.9 (T1)%/h) and a weight loss of 10.4 kg (9.9%) was observed. Subjects on 120 mg orlistat lost 2.5 kg (2.5%) after 1 month, and 9.8 kg (9.9%) after 1 year. Basal and postprandial CCK release decreased significantly after the first month of orlistat treatment but normalized after 1 year. Diet and lipase inhibition did not have any influence on gastric emptying. Conclusion: Energy and fat restriction of 1 month did not alter gastric emptying in the whole group. Continuation of the diet for 1 year resulted in a delayed gastric emptying of solids. Lipase inhibition did not result in a sustained depressed CCK release and the anticipated acceleration of gastric emptying did not occur.

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Gastrointestinal hormones and gastric emptying 20 years after jejunoileal bypass for massive obesity

Cited by 182 publications

References 17 publications

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

Treatment of morbid obesity by intraparietogastric administration of botulinum toxin: a randomized, double-blind, controlled study

Influences of fat restriction and lipase inhibition on gastric emptying in obesity

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