The MC4R genotype is associated with postpartum weight reduction and glycemic changes among women with prior gestational diabetes: longitudinal analysis

Carvalho, Aline Martins de; Shao, Ping; Liu, Huikun; Cheng, Han-Ling; Zheng, Yan; Leng, Junhong; Li, Weiqin; Huang, Tao; Wang, Tiange; Wang, Leishen; Zhang, Shuang; Hu, Gang; Qi, Lü

doi:10.1038/s41598-017-10101-x

Cited by 8 publications

(8 citation statements)

References 27 publications

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“…MC4R has been associated with key components of appetite, food intake, nutrient absorption, thermogenesis, energy expenditure, insulin secretion, obesity, and lipid metabolism (37). It is indicated that MC4R rs6567160 is associated with postpartum weight reduction and glycemic changes among women with prior GDM (38). Moreover, a significant correlation was observed between lipid parameters and MC4R rs17782313 (39).…”

Section: Discussionmentioning

confidence: 99%

Genetic Susceptibility to Gestational Diabetes Mellitus in a Chinese Population

et al. 2020

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Introduction: New genetic variants associated with susceptibility to obesity and metabolic diseases have been discovered in recent genome-wide association (GWA) studies. The aim of this study was to investigate the association of theses risk variants with gestational diabetes mellitus (GDM). Methods: We performed a case-control study including 964 unrelated pregnant women with GDM and 1,021 pregnant women with normal glucose tolerance (as controls). A total of 33 genetic variants confirmed by GWA studies for obesity and metabolic diseases were selected and measured. Results: We observed that FTO rs1121980 and KCNQ1 rs163182 conferred a decreased GDM risk in the dominant and additive model [additive model: OR (95% CI) = 0.79 (0.67-0.94), P = 0.007 for rs1121980; OR(95%CI) = 0.84 (0.73-0.96), P = 0.009 for rs163182], whereas MC4R rs12970134 and PROX1 rs340841 conferred an increased GDM risk in the dominant, recessive, and additive model [additive model: OR(95%CI) = 1.25 (1.07-1.46), P = 0.006 for rs12970134; OR(95%CI) = 1.22 (1.07-1.39), P = 0.002 for rs340841). With the increasing number of risk alleles of the four significant SNPs, GDM risk was significantly increased in a dose-dependent manner (P trend < 0.001). And the significant positive associations between the weighted genetic risk score and risk of GDM persisted. Further function annotation indicated that these four SNPs may fall on the functional elements of human pancreatic islets. The genotype-phenotype associations indicated that these SNPs may contribute to GDM by affecting the expression levels of their nearby or distant genes. Conclusion: Our study suggests that FTO rs1121980, KCNQ1 rs163182, MC4R rs12970134, and PROX1 rs340841 may be markers for susceptibility to GDM in a Chinese population.

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Section: Discussionmentioning

confidence: 99%

Genetic Susceptibility to Gestational Diabetes Mellitus in a Chinese Population

et al. 2020

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“…Recently, GWAs demonstrated MC4R to be one of the genes, which associates with common obesity [4,5]. The common polymorphism rs17782313 has recently been found to be unequivocally associated with obesity-related phenotypes in adults and children in different ethnicity and age groups [9,10,15].…”

Section: Discussionmentioning

confidence: 99%

“…have evidenced the association of common variants of several genes with obesty and other measurements of obesity [2,3]. Among these genes, the melanocortin-4 receptor (MC4R) gene has been considered to confer obesity risk [4,5]. MC4R gene (18q22) is a 322-amino acid; which belongs to the family of seventransmembrane, G-protein-linked receptor involved in central regulation of energy homeostasis, such as hypothalamus, brainstem, and other brain dopamine-rich regions [6][7][8].…”

Section: Introduction mentioning

confidence: 99%

Associations of single nucleotide polymorphism rs17782313 in melanocortin 4 receptor gene with anthropometric indices in normal and obesity primary school children in Hanoi

Tuyet¹

2018

MPS

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Melanocortin-4 receptor (MC4R) has roles in regulating food intake and energy balance. A number of studies have reported that variant rs17782313 is significantly associated with obesity in many populations. However, their contribution to obesity in the Vietnamese population is not fully described. The purpose of the present study was to evaluate the association of rs17782313 with anthropometric indices and obesity in the Vietnamese children population. A case-control study was conducted on 559 children aged 6-11 years (278 obese cases and 281 normal controls). The nutrition status of the children was classified using both criteria of International Obesity Task Force 2000 and World Health Organization 2007. The results showed that in normal group, the data of z score of weight for age was highest in CC genotype group and was lowest in TT genotype group (0.11 and -0.38 respectively, P=0.023). In obese group, the waist hip ratio was lowest in TT genotype group and the highest one was in CC genotype group (0.93 and 0.97 respectively, P=0.031). Our findings indicate that the variant rs17782313 near MC4R is likely to have an impact on the changing of weight and central obesity in the Vietnamese children.

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“…Lorcaserin, a 5-HT2CR agonist used as anti-obesity drug, decreases glycemia by acting on MC4R cholinergic neurons (Burke et al 2017). Interestingly, an association has been found between MC4R genotype and postpartum glycemic changes in humans, thus highlighting the relevance of MC4R in glucose metabolism in humans (de Carvalho et al 2017). Cholinergic parasympathetic MC4R neurons, such as those localized in the dorsal motor nucleus of the vagus (DMV) control insulin levels and gastric motility (Rossi et al 2011, Richardson et al 2013.…”

Section: Mc4r Neuronsmentioning

confidence: 99%

The melanocortin pathway and control of appetite-progress and therapeutic implications

Baldini

Phelan

2019

Journal of Endocrinology

185

125

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The initial discovery thatob/obmice become obese because of a recessive mutation of the leptin gene has been crucial to discover the melanocortin pathway to control appetite. In the melanocortin pathway, the fed state is signaled by abundance of circulating hormones such as leptin and insulin, which bind to receptors expressed at the surface of pro-opiomelanocortin (POMC) neurons to promote processing of POMC to the mature hormone α-melanocyte-stimulating hormone (α-MSH). The α-MSH released by POMC neurons then signals to decrease energy intake by binding to melanocortin-4 receptor (MC4R) expressed by MC4R neurons to the paraventricular nucleus (PVN). Conversely, in the ‘starved state’ activity of agouti-related neuropeptide (AgRP) and of neuropeptide Y (NPY)-expressing neurons is increased by decreased levels of circulating leptin and insulin and by the orexigenic hormone ghrelin to promote food intake. This initial understanding of the melanocortin pathway has recently been implemented by the description of the complex neuronal circuit that controls the activity of POMC, AgRP/NPY and MC4R neurons and downstream signaling by these neurons. This review summarizes the progress done on the melanocortin pathway and describes how obesity alters this pathway to disrupt energy homeostasis. We also describe progress on how leptin and insulin receptors signal in POMC neurons, how MC4R signals and how altered expression and traffic of MC4R change the acute signaling and desensitization properties of the receptor. We also describe how the discovery of the melanocortin pathway has led to the use of melanocortin agonists to treat obesity derived from genetic disorders.

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The MC4R genotype is associated with postpartum weight reduction and glycemic changes among women with prior gestational diabetes: longitudinal analysis

Cited by 8 publications

References 27 publications

Genetic Susceptibility to Gestational Diabetes Mellitus in a Chinese Population

Genetic Susceptibility to Gestational Diabetes Mellitus in a Chinese Population

Associations of single nucleotide polymorphism rs17782313 in melanocortin 4 receptor gene with anthropometric indices in normal and obesity primary school children in Hanoi

The melanocortin pathway and control of appetite-progress and therapeutic implications

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