The<i>MC4R(I251L</i>) Allele Is Associated with Better Metabolic Status and More Weight Loss after Gastric Bypass Surgery

Mirshahi, Uyenlinh L.; Still, Christopher D.; Masker, Kathryn; Gerhard, Glenn S.; Carey, David J.; Mirshahi, Tooraj

doi:10.1210/jc.2011-1549

Cited by 62 publications

(60 citation statements)

References 26 publications

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“…These studies suggest either that non-MC4R-mediated mechanisms by which RYGBP affects energy balance are not powerful enough to overcome complete absence of MC4R signaling or that the MC4R system is intrinsic to the biological response to RYGBP ( Figure 2). Importantly, carriers of a MC4R variant (I251L), known to increase basal MC4R activity, experience significantly greater weight loss after RYGBP compared with noncarriers or carriers of other MC4R variants (122). Understanding the role of MC4R in mediating the biological response to RYGBP could yield important insights into how RYGBP results in resetting the body weight set-point (29).…”

Section: Role Of the Mc4r Pathwaymentioning

confidence: 99%

Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms

Manning¹,

Pucci²,

Batterham³

2015

J. Clin. Invest.

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Section: Role Of the Mc4r Pathwaymentioning

confidence: 99%

Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms

Manning¹,

Pucci²,

Batterham³

2015

J. Clin. Invest.

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“…Most of the recent animal studies and some studies in humans have examined the role of the melanocortin system, which seems to be central to many peripheral and brain-derived stimuli that control eating and body weight (55,92,93,157). In humans, the sufficiency of one functional MC4r gene for effective RYGB outcome was indicated in some studies, including RYGB or VSG-operated humans (157).…”

Section: Cns Eating and Body Weight Controls After Rygbmentioning

confidence: 99%

“…In humans, the sufficiency of one functional MC4r gene for effective RYGB outcome was indicated in some studies, including RYGB or VSG-operated humans (157). However, the important role of the melanocortin system was supported by findings in humans with a specific variant of the MC4 gene [MC4r(I251L)], which is associated with a better metabolic status; in fact, carriers of this variant had improved surgery outcome (92,157).…”

Section: Cns Eating and Body Weight Controls After Rygbmentioning

confidence: 99%

The physiology underlying Roux-en-Y gastric bypass: a status report

Lutz

Bueter

2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Lutz TA, Bueter M. The physiology underlying Roux-en-Y gastric bypass: a status report. Am J Physiol Regul Integr Comp Physiol 307: R1275-R1291, 2014. First published September 24, 2014 doi:10.1152/ajpregu.00185.2014.-Obesity and its related comorbidities can be detrimental for the affected individual and challenge public health systems worldwide. Currently, the only available treatment options leading to clinically significant and maintained body weight loss and reduction in obesity-related morbidity and mortality are based on surgical interventions. This review will focus on two main clinical effects of Roux-en-Y gastric bypass (RYGB), namely body weight loss and change in eating behavior. Animal experiments designed to understand the underlying physiological mechanisms of these post-gastric bypass effects will be discussed. Where appropriate, reference will also be made to vertical sleeve gastrectomy. While caloric malabsorption and mechanical restriction seem not to be major factors in this respect, alterations in gut hormone levels are invariably found after RYGB. However, their causal role in RYGB effects on eating and body weight has recently been challenged. Other potential factors contributing to the RYGB effects include increased bile acid concentrations and an altered composition of gut microbiota. RYGB is further associated with remarkable changes in preference for different dietary components, such as a decrease in the preference for high fat or sugar. It needs to be noted, however, that in many cases, the question about the necessity of these alterations for the success of bariatric surgery procedures remains unanswered.Roux-en-Y gastric bypass; vertical sleeve gastrectomy; gut hormones; restriction; malabsorption; energy expenditure THE OBESITY EPIDEMIC AND ITS related comorbidities constitute a major challenge for both personal health and public health systems worldwide. The enormous increase in knowledge about the physiological mechanisms that control eating and body weight contrasts with the lack of available pharmacological therapies leading to safe, efficient, and long-lasting body weight reductions and amelioration of obesity-related comorbidities. However, recent insights into underlying mechanisms of obesity and bariatric surgery have led to promising perspectives in respect to gut hormone-based strategies against obesity. Nevertheless, best results for maintained weight reduction and improvement of comorbidities are still achieved by surgical means (22,88,121,135,136). This review aims to summarize key findings in respect to underlying physiological mechanisms of the Roux-en-Y gastric bypass (RYGB) procedure, which is the most commonly performed bariatric operation worldwide and thus, by many is considered as the gold standard in bariatric surgery. Sporadic reference will also be made to vertical sleeve gastrectomy (VSG) when appropriate. Both operations reduce eating at least temporarily (19,140,143) and lead to changes in food preferences (20,27,72). The majority of data collected with...

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“…Remarkably little is known about specific effects of RYGB (or other bariatric surgery procedures) on the CNS centers that are involved in eating control; most of the recent studies examined the role of the melanocortin system given its overall importance in the control of eating and body weight [64][65][66][67][68][69][70][71] . An unexplained species difference may be present; while homo-and heterozygous melanocortin-4 receptor (MC4r) knockout rats appeared to be fully responsive to weight-reducing VSG surgery [71] , homozygous MC4r knockout mice lost less weight after RYGB than heterozygous knockout or wild-type mice [67] .…”

Section: Central Nervous System Contribution To the Eating-inhibitorymentioning

confidence: 99%

Physiological Mechanisms behind Roux-en-Y Gastric Bypass Surgery

Lutz¹,

Bueter

2014

Dig Surg

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Obesity and its related comorbidities can be detrimental for the affected individual and challenge public health systems worldwide. Currently, the only available treatment options leading to clinically significant and maintained body weight loss and reduction in obesity-related morbidity and mortality are based on surgical interventions. Apart from the 'gold standard' Roux-en-Y gastric bypass (RYGB), the vertical sleeve gastrectomy and gastric banding are two frequently performed procedures. This review will discuss animal experiments designed to understand the underlying mechanisms of body weight loss after bariatric surgery. While caloric malabsorption and mechanical restriction are no major factors in this respect, alterations in gut hormone levels are invariably found after RYGB. However, their causal role in RYGB effects on eating and body weight has recently been challenged. Other potential factors contributing to the RYGB effects include increased bile acid concentrations and an altered composition of gut microbiota. RYGB is further associated with remarkable changes in the preference for different dietary components such as a decrease in the preference for high fat or sugar; it is important to note that the contribution of altered food preferences to the RYGB effects on body weight is not clear. high fat or sugar; it is important to note that the contribution of altered food preferences to the RYGB effects on body weight is not clear.

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TheMC4R(I251L) Allele Is Associated with Better Metabolic Status and More Weight Loss after Gastric Bypass Surgery

Abstract: Individuals carrying the I251L common allele are predisposed to better clinical outcome, reduced risk of type 2 diabetes, and better weight loss during diet and surgical interventions. Diabetic status has only a small, short-term effect on weight loss after RYGB.

Cited by 62 publications

References 26 publications

Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms

Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms

The physiology underlying Roux-en-Y gastric bypass: a status report

Physiological Mechanisms behind Roux-en-Y Gastric Bypass Surgery

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