C Borg

Gut Hormone Profiles Following Bariatric Surgery Favor an Anorectic State, Facilitate Weight Loss, and Improve Metabolic Parameters

Objective:To study the effect of bariatric surgery on the entero-hypothalamic endocrine axis of humans and rodents. Background:Bariatric surgery is the most effective obesity treatment as it achieves substantial and sustained weight loss. Glycemic control and enhanced satiation improve before substantial weight loss occurs. Gut peptides, acting both peripherally and centrally, contribute to glycemic control and regulate food intake. Methods:We examined meal-stimulated responses of insulin, ghrelin, peptide YY (PYY), glucagon-like-peptide-1 (GLP-1), and pancreatic polypeptide (PP) in humans and rodents following different bariatric surgical techniques. Results:Compared with lean and obese controls, patients following Roux-en-Y gastric bypass (RYGB) had increased postprandial plasma PYY and GLP-1 favoring enhanced satiety. Furthermore, RYGB patients had early and exaggerated insulin responses, potentially mediating improved glycemic control. None of these effects were observed in patients losing equivalent weight through gastric banding. Leptin, ghrelin, and PP were similar in both the surgical groups. Using a rodent model of jejuno-intestinal bypass (JIB), we showed elevated PYY and GLP-1 in JIB rats compared with sham-operated rats. Moreover, exogenous PYY reduced food intake and blockade of endogenous PYY increased food intake. Thus, higher plasma PYY following JIB may contribute to reduced food intake and contribute to weight loss. Conclusions:Following RYGB and JIB, a pleiotropic endocrine response may contribute to the improved glycemic control, appetite reduction, and long-term changes in body weight.

Progressive rise in gut hormone levels after Roux-en-Y gastric bypass suggests gut adaptation and explains altered satiety.

Bariatric surgery is the most effective treatment for achieving long‐term weight loss in morbidly obese patients. This study investigated prospective changes in gut hormones and metabolic indices after Roux‐en‐

Gut hypertrophy after gastric bypass is associated with increased glucagon-like peptide 2 and intestinal crypt cell proliferation.

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Supraphysiological doses of intravenous PYY3-36 cause nausea, but no additional reduction in food intake

gastric bypass (RYGB).

Attenuated peptide YY release in obese subjects is associated with reduced satiety

Objective:We aimed to determine changes in crypt cell proliferation and glucagon-like peptide-2 (GLP-2) in rodents and man after Roux-en-Y gastric bypass (RYGB). Summary of Background Data:Roux-en-Y gastric bypass results in sustained weight loss and reduced appetite with only mild gastrointestinal side effects. Glucagon-like peptide-2 released from intestinal l-cells after nutrient intake stimulates intestinal crypt cell proliferation and mitigates the effects of gut injury. Methods:Wistar rats underwent either RYGB (n = 6) or sham procedure (n = 6) and plasma GLP-2, GLP-1, and gut hormone peptide YY (PYY) were measured after 23 days. Biopsies from the terminal ileum were stained using the antibody to Ki67, which detects cyclins and hence demonstrates cells in the S-phase of the cell cycle. The total number of cells, number of mitosis, and number of labeled cells per crypt were counted. Obese patients (n = 6) undergoing RYGB were evaluated following a 420 kcal meal preoperatively, and 1, 3, 6, 12, and 24 months later for responses in l-cell products such as GLP-2, GLP-1, total PYY, and PYY3–36. Results:Rat GLP-2 levels after RYGB were elevated 91% above sham animals (P = 0.02). At necropsy, mitotic rate (P < 0.001) and cells positive for the antibody Ki67 (P < 0.001) were increased, indicating crypt cell proliferation. Human GLP-2 after RYGB reached a peak at 6 months of 168% (P < 0.01) above preoperative values. Area under the curve for GLP-1 (P < 0.0001), total PYY (P < 0.01), and PYY3–36 (P < 0.05) responses increased progressively over 24 months. Conclusions:RYGB leads to increased GLP-2 and mucosal crypt cell proliferation. Other gut hormones from l-cells remain elevated for at least 2 years in humans. These findings may account for the restoration of the absorptive surface area of the gut, which limits malabsorption and contributes to the long-term weight loss after RYGB.

Biliopancreatic diversion in rats is associated with intestinal hypertrophy and with increased GLP-1, GLP-2 and PYY levels.

Abstract Background Peptide YY (PYY3-36) infused to levels within the physiological range reduces appetite and food intake in humans without nausea. However, PYY3-36 has previously been shown to cause nausea at higher doses. Methods We studied the relationship of PYY3-36, nausea and food intake in six volunteers, using three different PYY3-36 preparations infused to achieve supraphysiological PYY plasma levels. Results Supraphysiological levels of PYY caused nausea in five subjects (P < 0.05). Although PYY3-36 increased satiety (P < 0.05) and reduced food intake (P < 0.05), no greater enhancement of satiety or inhibition of food intake was observed compared with previous reports. Conclusions This study cautions against the use of supraphysiological doses of PYY3-36 as it may increase nausea with no benefit in food reduction.