A variant near the melanocortin-4 receptor gene regulates postprandial lipid metabolism in a healthy Caucasian population

The melanocortin-4 receptor (MC4R) is an essential regulator of food intake and energy homeostasis. Previous data suggest an influence of MC4R activity on TAG levels. Thus, the aim of the present study was to determine whether the presence of the rs12970134 polymorphism near theMC4Rgene could influence postprandial lipoprotein metabolism in healthy subjects. A total of eighty-eight volunteers were selected, fifty-three homozygous for the common genotype (G/G) and thirty-five carriers for the minor A-allele (G/A and A/A). They were given a fat-rich meal containing 1 g fat and 7 mg cholesterol/kg body weight and vitamin A (60 000 IU/m2body surface). Fat accounted for 60 % of energy, and protein and carbohydrates accounted for 15 and 25 % of energy, respectively. Blood samples were taken at time 0, every 1 h until 6 h and every 2·5 h until 11 h. Total cholesterol and TAG in plasma, and cholesterol, TAG and retinyl palmitate in TAG-rich lipoproteins (TRL, large and small TRL) were separated by ultracentrifugation. Individuals carrying the G/G genotype displayed a higher postprandial response of plasma TAG (P = 0·033), total cholesterol (P = 0·019) and large TRL–TAG (P = 0·023) than did carriers of the minor A-allele. Furthermore, G/G subjects showed a greater postprandial response of small TRL–apoB48 than did carriers of the A-allele (P = 0·032). These results suggest that the rs12970134 polymorphism near theMC4Rgene region may partly explain the inter-individual differences in postprandial lipoprotein response in healthy subjects.

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Food demand and meal size in mice with single or combined disruption of melanocortin type 3 and 4 receptors

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00562.2009 ◽

2010 ◽

Vol 298 (6) ◽

pp. R1667-R1674 ◽

Cited By ~ 30

Author(s):

Deniz Atalayer ◽

Kimberly L. Robertson ◽

Carrie Haskell-Luevano ◽

Amy Andreasen ◽

Neil E. Rowland

Keyword(s):

Energy Homeostasis ◽

Receptor Gene ◽

Gut Hormones ◽

Brain Regions ◽

Meal Size ◽

Food Demand ◽

Double Knockout ◽

Melanocortin 4 Receptor ◽

Melanocortin 4 Receptor Gene ◽

Anorectic Effect

Mice with homozygous genetic disruption of the melanocortin-4 receptor gene (MC4R−/−) are known to be hyperphagic and become obese, while those with disruption of the melanocortin-3 receptor gene (MC3R−/−) do not become markedly obese. The contribution of MC3R signaling in energy homeostasis remains little studied. In the present work, we compare MC3R−/− mice with wild-type (WT), MC4R−/−, and mice bearing disruption of both genes (double knockout, DKO) on select feeding and neuroanatomical dimensions. DKO mice were significantly more obese than MC4R−/−, whereas MC3R−/− weighed the same as WT. In a food demand protocol, DKO and MC4R−/− were hyperphagic at low unit costs for food, due primarily to increased meal size. However, at higher costs, their intake dropped below that of WT and MC3R−/−, indicating increased elasticity of food demand. To determine whether this higher elasticity was due to either the genotype or to the obese phenotype, the same food demand protocol was conducted in dietary obese C57BL6 mice. They showed similar elasticity to lean mice, suggesting that the effect is of genotypic origin. To assess whether the increased meal size in MC4R−/− and DKO might be due to reduced CCK signaling, we examined the acute anorectic effect of peripherally administered CCK and subsequently the induction of c-Fos immunoreactivity in select brain regions. The anorectic effect of CCK was comparable in MC4R−/− , DKO, and WT, but it was unexpectedly absent in MC3R−/−. CCK-induced c-Fos was lower in the paraventricular nucleus in MC3R−/− than the other genotypes. These data are discussed in terms of demand functions for food intake, MC receptors involved in feeding, and their relation to actions of gut hormones, such as CCK, and to obesity.

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Analysis of variation in the melanocortin-4 receptor gene (mc4r) in golden retriever dogs

Animal Genetics ◽

10.1111/j.1365-2052.2010.02049.x ◽

2010 ◽

Vol 41 (5) ◽

pp. 557-557 ◽

Cited By ~ 16

Author(s):

L. Van Den Berg ◽

S. M. Van Den Berg ◽

E. E. C. P. Martens ◽

H. A. W. Hazewinkel ◽

N. A. Dijkshoorn ◽

...

Keyword(s):

Receptor Gene ◽

Golden Retriever ◽

Melanocortin 4 Receptor ◽

Melanocortin 4 Receptor Gene ◽

Analysis Of Variation

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Melanocortin-4 Receptor Gene Variation Is Associated with Eating Behavior in Chilean Adults

Annals of Nutrition and Metabolism ◽

10.1159/000439092 ◽

2015 ◽

Vol 68 (1) ◽

pp. 35-41 ◽

Cited By ~ 15

Author(s):

Javier A. Vega ◽

Gloria Salazar ◽

María Isabel Hodgson ◽

Luis Rodrigo Cataldo ◽

Macarena Valladares ◽

...

Keyword(s):

Eating Behavior ◽

Emotional Eating ◽

Leptin Receptor ◽

Receptor Gene ◽

Pathogenic Mutation ◽

Gene Variation ◽

Mc4r Gene ◽

Melanocortin 4 Receptor ◽

Melanocortin 4 Receptor Gene ◽

Mc4r Rs17782313

Background/Aims: To evaluate the association between allelic variants of melanocortin receptors -3 and -4 (MC3R and MC4R, respectively) and leptin receptor (LEPR) genes with body mass index (BMI) and eating behavior. Methods: We selected 344 Chilean adults (57.8% women; age 39.1 ± 6.6 years) with a wide variation in BMI (30.3 ± 6.3 kg/m2). The Three-Factor Eating Questionnaire-R18 that measures uncontrolled eating (UE), emotional eating (EE) and cognitive restraint scores was adapted, validated and assessed for association with BMI. Genotypes were determined by polymerase chain reaction followed by restriction fragment length polymorphism techniques and Taqman assays. Results: Higher EE scores were found in obese vs. non-obese in both men (p = 0.01) and women (p < 0.001). UE scores were significantly associated with BMI only in women (p = 0.002). No significant differences in eating behavior scores or BMI were found by LEPR (rs1137101, rs8179183 and rs1137100 polymorphisms) or MC3R (rs3746619 and rs3827103). Carriers of the C allele for MC4R rs17782313 showed significantly higher scores of UE compared to non-carriers (2.3 ± 0.8 vs. 2.0 ± 0.7; p = 0.02). Additionally, we also report a monogenic case of obesity carrying the pathogenic mutation 449C>T (Thr150Ile) in MC4R gene with no apparent alterations in eating behavior scores. Conclusions: UE scores were higher in C-allele carriers of MC4R-rs17782313 compared to non-carriers.

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Growth, fattening and meat guality parameters among young pigs with different snp genotypes of melanocortin – 4 receptor gene (mc4r)

The Scientific Journal Grain Crops ◽

10.31867/2523-4544/0069 ◽

2019 ◽

Vol 3 (1) ◽

pp. 127-132

Author(s):

V. I. Khalak ◽

Keyword(s):

Receptor Gene ◽

Young Pigs ◽

Melanocortin 4 Receptor ◽

Melanocortin 4 Receptor Gene

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Melanocortin-4 Receptor Gene Mutations in Obese Slovak Children

Physiological Research ◽

10.33549/physiolres.932968 ◽

2015 ◽

pp. 883-890 ◽

Cited By ~ 2

Author(s):

D. STANIKOVA ◽

M. SUROVA ◽

L. TICHA ◽

M. PETRASOVA ◽

D. VIRGOVA ◽

...

Keyword(s):

Sanger Sequencing ◽

Dna Analysis ◽

Receptor Gene ◽

Gene Mutations ◽

Loss Of Function ◽

Obese Children ◽

Mc4r Gene ◽

Melanocortin 4 Receptor ◽

Melanocortin 4 Receptor Gene ◽

Common Etiology

The most common etiology of non-syndromic monogenic obesity are mutations in gene for the Melanocortin-4 receptor (MC485) with variable prevalence in different countries (1.2-6.3 % of obese children). The aim of our study was 1) to search for MC4R mutations in obese children in Slovakia and compare their prevalence with other European countries, and 2) to describe the phenotype of the mutation carriers. DNA analysis by direct Sanger sequencing of the coding exons and intron/exon boundaries of the MC4R gene was performed in 268 unrelated Slovak children and adolescents with body mass index above the 97th percentile for age and sex and obesity onset up to 11 years (mean 4.3±2.8 years). Two different previously described heterozygous loss of function MC4R variants (i.e. p.Ser19Alafs*34, p.Ser127Leu) were identified in two obese probands, and one obese (p.Ser19Alafs*34), and one lean (p.Ser127Leu) adult family relatives. No loss of function variants were found in lean controls. The prevalence of loss-of-function MC4R variants in obese Slovak children was 0.7 %, what is one of the lowest frequencies in Europe.

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