Bariatric surgery in a patient with complete MC4R deficiency

Aslan, Ivy R.; Ranadive, Sayali A.; Ersoy, Baran A.; Rogers, Stanley J.; Lustig, Robert H.; Vaisse, Christian

doi:10.1038/ijo.2010.168

Cited by 62 publications

(50 citation statements)

References 24 publications

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“…Laparoscopic adjustable gastric banding did not result in a long-term weight reduction in an 18-years old patient with complete MC4R deficiency [217], and was associated with a high risk of conversion to bypass operations in individuals with partial MC4R deficiency [218]. On the other hand, three studies confirmed that Roux-en-Y gastric bypass surgery was an efficient strategy to lose weight in MC4R mutation carriers [219][220][221].…”

Section: Obesity-predisposing Gene Variants Interact With Bariatric Smentioning

confidence: 93%

The importance of gene–environment interactions in human obesity

2016

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The worldwide obesity epidemic has been mainly attributed to lifestyle changes. However, who becomes obese in an obesity-prone environment is largely determined by genetic factors. In the last 20 years, important progress has been made in the elucidation of the genetic architecture of obesity. In parallel with successful gene identifications, the number of gene-environment interaction (GEI) studies has grown rapidly. This paper reviews the growing body of evidence supporting gene-environment interactions in the field of obesity. Heritability, monogenic and polygenic obesity studies provide converging evidence that obesity-predisposing genes interact with a variety of environmental, lifestyle and treatment exposures. However, some skepticism remains regarding the validity of these studies based on several issues, which include statistical modelling, confounding, low replication rate, underpowered analyses, biological assumptions and measurement precision. What follows in this review includes (1) an introduction to the study of GEI, (2) the evidence of GEI in the field of obesity, (3) an outline of the biological mechanisms that may explain these interaction effects, (4) methodological challenges associated with GEI studies and potential solutions, and (5) future directions of GEI research. Thus far, this growing body of evidence has provided a deeper understanding of GEI influencing obesity and may have tremendous applications in the emerging field of personalized medicine and individualized lifestyle recommendations.

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Section: Obesity-predisposing Gene Variants Interact With Bariatric Smentioning

confidence: 93%

The importance of gene–environment interactions in human obesity

2016

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“…Thus, MC4R might well be important in the efficacy of bariatric surgical procedures. MC4R-deficient rats have been developed recently (18), and their relatively larger size makes the rat better suited than the mouse for mechanistic studies of bariatric surgery.Although the impact of MC4R mutations has been studied in combination with RYGB and gastric banding [a procedure that physically limits the diameter of the upper part of the stomach to reduce food intake (3,4,14)], it is unknown whether VSG still has beneficial effects in humans or rodents that are partially or completely deficient for MC4R. Therefore, we used wild-type (WT), Mc4r ϩ/Ϫ , and Mc4r Ϫ/Ϫ rats (18) to determine whether MC4R function is necessary for producing the beneficial effects of VSG with regard to body weight, glucose metabolism, and macronutrient preference.…”

mentioning

confidence: 99%

Effect of vertical sleeve gastrectomy in melanocortin receptor 4-deficient rats

Mul

Begg

Alsters

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Bariatric surgery is currently the most effective treatment for obesity. Vertical sleeve gastrectomy (VSG), a commonly applied bariatric procedure, involves surgically incising most of the volume of the stomach. In humans, partial loss of melanocortin receptor-4 (MC4R) activity is the most common monogenic correlate of obesity regardless of lifestyle. At present it is unclear whether genetic alteration of MC4R signaling modulates the beneficial effects of VSG. Following VSG, we analyzed body weight, food intake, glucose sensitivity, and macronutrient preference of wild-type and MC4R-deficient (Mc4r(+/-) and Mc4r(-/-)) rats compared with sham-operated controls. VSG reduced body weight and fat mass and improved glucose metabolism and also shifted preference toward carbohydrates and away from fat. All of this occurred independently of MC4R activity. In addition, MC4R was resequenced in 46 human subjects who underwent VSG. We observed common genetic variations in the coding sequence of MC4R in five subjects. However, none of those variations appeared to affect the outcome of VSG. Taken together, these data suggest that the beneficial effect of VSG on body weight and glucose metabolism is not mediated by alterations in MC4R activity.

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“…For example, older people and people with type 2 diabetes tend to lose less weight. Interestingly, the effects of bariatric surgery on weight loss appear to be dependent on MC4R in homozygous knockout animal models (71) and in humans with complete MC4R deficiency (72). However, patient heterozygosity for obesity-producing MC4R mutations does not affect the response to bariatric surgery (73,74).…”

Section: Physiological Mechanisms and Effectiveness Of Bariatric Surgerymentioning

confidence: 99%