Melanocortin-4 Receptor Mutations and Polymorphisms Do Not Affect Weight Loss after Bariatric Surgery

Valette, Marion; Poitou, Christine; Beyec, Johanne Le; Bouillot, Jean‐Luc; Clément, Karine; Czernichow, Sébastien

doi:10.1371/journal.pone.0048221

Cited by 80 publications

(42 citation statements)

References 21 publications

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“…In a systematic review of 61 studies (involving 80,957 obese and 220,223 controls), rs17782313 polymorphism was significantly associated with obesity risk (OR 1.18, 95 % CI 1.15-1.21, p = 0.001) (Xi et al 2012). The effects of MC4R and rs17782313 polymorphisms on eating behavior were recently reviewed by Valette et al (2012) and Hinney et al 2013 These large population-based studies focused on body mass phenotype and indicated a relationship between rs17782313 and obesity. In addition, there are mechanistic insights that suggest the genetic variation rs17782313 may influence 'reward' mechanisms, particularly in females.…”

Section: Introductionmentioning

confidence: 99%

Association of melanocortin 4 receptor gene variation with satiation and gastric emptying in overweight and obese adults

et al. 2014

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Melanocortin 4 receptor (MC4R) has a major role in energy homeostasis. The rs17782313 polymorphism, mapped 188 kb downstream from MC4R, has been associated with satiety, higher body mass index (BMI) and total calorie intake in adults. To assess the association of rs17782313 with gastric functions, satiation, or satiety, we studied 178 predominantly Caucasian overweight and obese people: 120 females, 58 males; mean BMI 33.4 ± 5.3 kg/m 2 (SD); age 37.7 ± 11.2 years. Quantitative traits assessed were gastric emptying (GE) of solids and liquids; fasting and postprandial gastric volume; satiation by maximum tolerated volume and 4 symptoms by 100-mm visual analog scales (VAS); and satiety by ad libitum buffet meal. Associations of genotype and quantitative traits were assessed by analysis of covariance (using gender and BMI as covariates), based on a dominant [TC (n = 72) -CC (n = 12) vs. TT (n = 94)] genetic model. rs17782313(C) was associated with postprandial satiation symptoms (median D total VAS 26.5 mm, p = 0.036), reduced proportion of solid GE at 2 h (median D 6.7 %, p = 0.008) and 4 h (median D 3.2 %, p = 0.006), and longer t (median D 6 min, p = 0.034). Associations of rs17782313 with obesity may be explained by reduced satiation and GE. The role of MC4R mechanisms in satiation and gastric function deserves further study.

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Section: Introductionmentioning

confidence: 99%

Association of melanocortin 4 receptor gene variation with satiation and gastric emptying in overweight and obese adults

et al. 2014

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“…We also reported outcomes of laparoscopic adjustable gastric banding (AGB) in 19 MC4R variant carriers, who had poorer outcomes at 3 years than noncarriers (10). This work has been followed by numerous conflicting publications regarding eating behavior and surgical outcomes in patients with rare and common genetic variants in MC4R (11)(12)(13)(14)(15)(16)(17)(18)(19). Main confounds are short follow-up, absence of stratification for sex and age, and underpowered study designs that impede analyses of mechanisms, potentially affecting outcomes (19).…”

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confidence: 99%

Eating Behavior, Low-Frequency Functional Mutations in the Melanocortin-4 Receptor (MC4R) Gene, and Outcomes of Bariatric Operations: A 6-Year Prospective Study

et al. 2016

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OBJECTIVEData on the effects of eating behavior and genetics on outcomes of gastrointestinal surgery for diabesity have been sparse, often flawed, and controversial. We aimed to assess long-term outcomes of bariatric operations in patients characterized for eating behavior and rare mutations in the melanocortin-4 receptor (MC4R) gene, which is strongly implicated in energy balance. RESEARCH DESIGN AND METHODSBetween 1996 and 2005, 1,264 severely obese Swiss patients underwent current laparoscopic adjustable gastric banding, gastroduodenal bypass, or a hybrid operation. Of these, 872 patients were followed for a minimum of 6 years and were screened for MC4R mutations. Using regression models, we studied relationships between eating behavior and MC4R mutations and postoperative weight loss, complications, and reoperations after 6 years. RESULTSAt baseline, rare functional MC4R mutation carriers exhibited a significantly higher prevalence of binge eating disorder (BED) or loss-of-control eating independent of age, sex, and BMI. Six years after bariatric surgery, the mutation carriers had more major complications than wild-type subjects independent of age, baseline BMI, sex, operation type, and weight loss. Furthermore, high baseline BMI, male sex, BED, and functional MC4R mutations were independent predictors of higher reoperation rates. CONCLUSIONSSequencing of MC4R and eating typology, combined with stratification for sex and baseline BMI, might significantly improve patient allocation to banding or bypass operations for diabesity as well as reduce both complication and reoperation rates.

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“…concluded that functional MC4R mutations and genetic variants did not influence weight loss and body composition after bariatric surgery [13]. The interpretation of the study results is limited; however, since the study did not assess weight loss maintenance in patients with the MC4R mutations compared with those without the mutations, only a few patients (n=9) were heterozygous for functional MC4R mutations, and the follow-up period after surgery was short.…”

Section: Current Research In Diabetes and Obesity Journalmentioning

confidence: 89%

“…Patients with the loss-of-function (LOF) MC4R mutation experience an increased appetite or hyperphagia, which may start in childhood. These mutations are considered to limit the extent to which weight loss or the maintenance of weight loss occurs with different weight reduction methods such as lifestyle intervention in children [11] and bariatric surgery for adolescent and adult patients [12][13][14].…”

Section: Current Research In Diabetes and Obesity Journalmentioning

confidence: 99%

pharmacoligical treatment of a pateint with lifelong obesity and heterozygous complete loss of function melonocortin 4 receptor mutation

Cooper¹

2016

CRDOJ

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The heterozygous melanocortin 4 receptor (MC4R) mutation is considered a primary factor in 2% to 4% of patients with obesity. Pharmacological treatment, including long-term, is emerging as a new standard for obese patients; however, there are no published reports on treatment outcomes in obese patients with documented MC4R mutations. Weight loss occurs with diet restriction or bariatric surgery and is often followed by a weight regain phase in patients with or without the MC4R mutation, indicating the need for an alternative approach to weight loss such as pharmacological treatment.This case study describes a 48-year-old woman who experienced lifelong obesity and a history of dieting that started in childhood with episodes of weight loss followed by weight gain. Her highest weight was 320 pounds in 2007. Her family's medical history included diabetes, prediabetes, and obesity. She presented to the clinic in January 2013 weighing 286.2 pounds with at-risk cardiovascular and cardiometabolic profiles. Treatment was initiated to control insulin resistance and metabolic syndrome, lower cholesterol and triglycerides, and manage hypothyroidism. Weight-loss treatment also began with a combination of bupropion and naltrexone or carbonic anhydrase inhibitors and naltrexone. Her on-treatment nutrition included eating from all food groups without counting calories or excessive exercise. In late 2014, she tested positive for a heterozygous complete loss-of-function MC4R gene mutation and weighed 213 pounds. The patient's lowest weight while on treatment was 166 pounds in August 2015. By November 2016, after experiencing partial weight regain, her weight had been stable for 6 months at approximately 198 pounds,a 30% reduction in weight from 2013.Pharmacological treatment is emerging as a recommended approach to weight loss. This case is an example of how, despite partial weight regain after weight loss, targeted pharmacological treatment can improve long-term outcomes including in patients with the MC4R complete loss-of-function mutation.

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Melanocortin-4 Receptor Mutations and Polymorphisms Do Not Affect Weight Loss after Bariatric Surgery

Cited by 80 publications

References 21 publications

Association of melanocortin 4 receptor gene variation with satiation and gastric emptying in overweight and obese adults

Association of melanocortin 4 receptor gene variation with satiation and gastric emptying in overweight and obese adults

Eating Behavior, Low-Frequency Functional Mutations in the Melanocortin-4 Receptor (MC4R) Gene, and Outcomes of Bariatric Operations: A 6-Year Prospective Study

pharmacoligical treatment of a pateint with lifelong obesity and heterozygous complete loss of function melonocortin 4 receptor mutation

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