Diet and Gastrointestinal Bypass–Induced Weight Loss

Chandarana, Keval; Gelegen, Çiğdem; Karra, Efthimia; Choudhury, Agharul I.; Drew, Megan E.; Fauveau, Véronique; Viollet, Benoı̂t; Andréelli, Fabrizio; Withers, Dominic J.; Batterham, Rachel L.

doi:10.2337/db10-0566

Cited by 133 publications

(85 citation statements)

References 42 publications

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“…However, it is possible that the drug lost efficacy over the 2 wk in the minipumps at body temperature. The lack of effect of Y2 receptor blockade in RYGB rats is in contrast to findings with a modified gastrointestinal bypass model in PYY-deficient mice (14). In that study, wild-type, but not mice with modified gastrointestinal bypass weighed significantly less 10 days after surgery compared with sham-operated mice, supporting a role for PYY in the acute effects of gastric bypass on body weight.…”

Section: Discussionmentioning

confidence: 72%

“…Because both of these gut hormones are hypersecreted after RYGB and sleeve gastrectomy, they are prime candidates for the weight-lowering effects of these two types of bariatric surgeries (e.g., 14,38). To test the hypothesis that either exaggerated GLP-1 or Y2 receptor signaling in the brain is responsible for the maintenance of a low body weight level after RYGB, we chronically infused the respective antagonists Ex9 or BIIE0246 into the brain over a period of 2 wk.…”

Section: Discussionmentioning

confidence: 99%

“…There have been only two attempts to mechanistically and directly test the role of endogenous GLP-1 and PYY in the weight-reducing effects of bariatric surgeries. In a study in PYY-deficient mice, the initial body weight loss after a modified gastric bypass surgery was greatly attenuated compared with wild-type mice, suggesting a role for exaggerated circulating levels of this gut peptide (14). In a study in GLP-1 receptor-deficient mice, sleeve gastrectomy was similarly effective compared with wild-type mice, suggesting that exaggerated circulating GLP-1 levels are not required for VSG's effects on weight loss and improvement of glycemic control (64).…”

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confidence: 99%

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GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents

Zheng

Mumphrey

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

160

114

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-Exaggerated GLP-1 and PYY secretion is thought to be a major mechanism in the reduced food intake and body weight after Roux-en-Y gastric bypass surgery. Here, we use complementary pharmacological and genetic loss-of-function approaches to test the role of increased signaling by these gut hormones in high-fat diet-induced obese rodents. Chronic brain infusion of a supramaximal dose of the selective GLP-1 receptor antagonist exendin-9 -39 into the lateral cerebral ventricle significantly increased food intake and body weight in both RYGB and sham-operated rats, suggesting that, while contributing to the physiological control of food intake and body weight, central GLP-1 receptor signaling tone is not the critical mechanism uniquely responsible for the body weightlowering effects of RYGB. Central infusion of the selective Y2R-antagonist BIIE0246 had no effect in either group, suggesting that it is not critical for the effects of RYGB on body weight under the conditions tested. In a recently established mouse model of RYGB that closely mimics surgery and weight loss dynamics in humans, obese GLP-1R-deficient mice lost the same amount of body weight and fat mass and maintained similarly lower body weight compared with wild-type mice. Together, the results surprisingly provide no support for important individual roles of either gut hormone in the specific mechanisms by which RYGB rats settle at a lower body weight. It is likely that the beneficial effects of bariatric surgeries are expressed through complex mechanisms that require combination approaches for their identification.Roux-en-Y gastric bypass; gut hormones; brain; GLP-1R knockout; food intake; exendin-(9 -39), BIIE0246; high-fat diet THE NUMBER OF BARIATRIC SURGERIES performed has steadily increased because for many obese patients, it is the last hope for significant and enduring body weight loss and general improvement of health. There have been an increasing number of clinical and preclinical studies with the goal to unravel the mechanisms underlying these beneficial effects of bariatric surgeries, but there has not yet been a breakthrough. A major hypothesis is that changes in gut hormone release are crucial. Drastically increased postprandial circulating levels of GLP-1 and PYY have been demonstrated in clinical studies (18,32,33,36,38,44,47,50) and in rodent models (13, 16, 37, 56) for both Roux-en-Y gastric bypass and vertical sleeve gastrectomy.GLP-1 is a powerful hormone that acts both in the periphery and brain to stimulate insulin secretion, inhibit gastric emptying, and suppress food intake (for recent reviews, see Refs. 7,12,43). Exogenous administration of GLP-1 or its stable analog exendin-4, as well as PYY(3-36), has been shown in numerous preclinical and clinical studies to suppress food intake and lower body weight (e.g., (2,4,5,9,15,19,24,27,40,57,59) or to suppress hepatic glucose production (52), in some of them by directly acting on the brain. The stable GLP-1 receptor agonist exendin-4 is widely used by Type 2 diabetic patients to sta...

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents

Zheng

Mumphrey

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

160

114

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“…It is conceivable that gut hormones such as Glucagon-like peptide 1 (GLP-1) acting via the hypothalamus may, improve glycaemic control in part by reducing calorie intake and body weight [5]. In addition, an increase in the colonic Peptide YY (PYY) expression has been shown in mice following gastrointestinal bypass surgery [6]. This gut hormone which normally rises post-prandially in proportion to caloric intake, is also associated with decreased appetite and reduced food intake [7].…”

Section: Discussionmentioning

confidence: 99%

Obesity and HIV Infection-is there a Role for Bariatric Surgery in Treatment?

Kapembwa¹

2014

J AIDS Clin Res

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Life expectancy of HIV-infected patients has improved in the recent decade with the use of antiretroviral therapy. Hence, more HIV-infected patients with chronic co-morbidities are being followed by different specialities. Diabetes and obesity are two of the co-morbidities. We looked at the outcome of bariatric surgery for 3 HIV-infected patients. We concluded that bariatric surgery is safe and can reduce pill burden. However, a multi-disciplinary team approach is needed to ensure that the right patients are selected and on-going support available to achieve the best outcome.

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“…51 However, subsequent studies in rodents directly testing roles for each of these gut hormones in the beneficial effects of RYGB and sleeve gastrectomy were largely negative. Neither GLP-1 receptor deficiency nor ghrelin deficiency appreciably changed the effects of RYGB 17,52 or sleeve gastrectomy, 53,54 and neither GLP-1 receptor nor PYY/Y2 receptor blockade in the brain attenuated RYGB-induced body weight suppression 17 (but see Chandarana et al 55 for a different outcome). Although these studies do not lend much support for individual roles of these hormones, it is possible that they act synergistically.…”

Section: Potential Underlying Mechanisms For Change In Set Pointmentioning

confidence: 98%

Does gastric bypass surgery change body weight set point?

et al. 2016

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The relatively stable body weight during adulthood is attributed to a homeostatic regulatory mechanism residing in the brain which uses feedback from the body to control energy intake and expenditure. This mechanism guarantees that if perturbed up or down by design, body weight will return to pre-perturbation levels, defined as the defended level or set point. The fact that weight re-gain is common after dieting suggests that obese subjects defend a higher level of body weight. Thus, the set point for body weight is flexible and likely determined by the complex interaction of genetic, epigenetic and environmental factors. Unlike dieting, bariatric surgery does a much better job in producing sustained suppression of food intake and body weight, and an intensive search for the underlying mechanisms has started. Although one explanation for this lasting effect of particularly Roux-en-Y gastric bypass surgery (RYGB) is simple physical restriction due to the invasive surgery, a more exciting explanation is that the surgery physiologically reprograms the body weight defense mechanism. In this non-systematic review, we present behavioral evidence from our own and other studies that defended body weight is lowered after RYGB and sleeve gastrectomy. After these surgeries, rodents return to their preferred lower body weight if over-or underfed for a period of time, and the ability to drastically increase food intake during the anabolic phase strongly argues against the physical restriction hypothesis. However, the underlying mechanisms remain obscure. Although the mechanism involves central leptin and melanocortin signaling pathways, other peripheral signals such as gut hormones and their neural effector pathways likely contribute. Future research using both targeted and non-targeted 'omics' techniques in both humans and rodents as well as modern, genetically targeted, neuronal manipulation techniques in rodents will be necessary.

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Diet and Gastrointestinal Bypass–Induced Weight Loss

Cited by 133 publications

References 42 publications

GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents

GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents

Obesity and HIV Infection-is there a Role for Bariatric Surgery in Treatment?

Does gastric bypass surgery change body weight set point?

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