The interaction between dietary approaches to stop hypertension and MC4R gene variant in predicting cardiovascular risk factors

Objective: The genetic variants near the melanocortin-4 receptor gene (MC4R), a key protein regulating energy balance and adiposity, have been related to obesity and cardiovascular risk factors. However, qualitative and quantitative aspects of diet may modulate the association of this polymorphism with obesity and cardiovascular diseases (CVDs). The aim of this study was to evaluate interactions among MC4R rs17782313, the Dietary Approaches to Stop Hypertension (DASH) diet and risk factors for CVDs. Method: This cross-sectional study was conducted on 266 Iranian women categorized by body mass index (BMI) range of 25–40 kg/m2 as overweight or obese. CVD risk factors included waist circumference (WC), lipid profile, blood pressure, insulin circulation and fasting blood sugar (FBS). Insulin and FBS were used to calculate homeostatic model assessment insulin resistance (HOMA-IR) Body composition was assessed by a multi-frequency bioelectrical impedance analyzer, InBody 770 scanner. Results: The findings of this study show that high adherence to the DASH diet in the CC groups were associated with decreased SBP and DBP compared to the TT group. In addition, a significant difference between women with high adherence to the DASH diet compared to low adherence was observed for body weight (p < 0.001), fat free mass (FFM) (p = 0.01) and BMI (p = 0.02). Women with the CC genotype had higher insulin (mg/dl) (mean and SD, for TT: 14.6 ± 4.6, TC: 17.3 ± 9.2, CC: 15.3 ± 4.8, p = 0.04) and HOMA-IR (mean for and SD, TT: 3.1 ± 1.07, TC: 3.9 ± 2.4, CC: 3.2 ± 1.1, p = 0.01) than TT group. Inclusion of potential confounding variables (age, physical activity, BMI and daily caloric intake) did not attenuate the difference. Conclusion: Among overweight/obese Iranian women with the CC genotype, incorporating the DASH diet may serve as a dietary prescription to decrease CVD risk. A dietary intervention trial is warranted.

Optogenetic stimulation of the liver-projecting melanocortinergic pathway promotes hepatic glucose production

The central melanocortin system plays a fundamental role in the control of feeding and body weight. Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) also regulate overall glucose homeostasis via insulin-dependent and -independent pathways. Here, we report that a subset of ARC POMC neurons innervate the liver via preganglionic parasympathetic acetylcholine (ACh) neurons in the dorsal motor nucleus of the vagus (DMV). Optogenetic stimulation of this liver-projecting melanocortinergic pathway elevates blood glucose levels that is associated with increased expression of hepatic gluconeogenic enzymes in female and male mice. Pharmacological blockade and knockdown of the melanocortin-4 receptor gene in the DMV abolish this stimulation-induced effect. Activation of melanocortin-4 receptors inhibits DMV cholinergic neurons and optogenetic inhibition of liver-projecting parasympathetic cholinergic fibers increases blood glucose levels. This elevated blood glucose is not due to altered pancreatic hormone release. Interestingly, insulin-induced hypoglycemia increases ARC POMC neuron activity. Hence, this liver-projecting melanocortinergic circuit that we identified may play a critical role in the counterregulatory response to hypoglycemia.

Prevalence and expressivity of loss of function mutations in the Melanocortin 4 Receptor (MC4R) in a UK birth cohort

ABSTRACTMutations in the melanocortin 4 receptor gene (MC4R) have frequently been reported in severe early-onset human obesity but the prevalence and extent of phenotypic impact of such mutations are unclear. In a large UK birth cohort, we found that 17 of 5724 unrelated participants (∼1/337; 0.30%) were heterozygous for functionally deleterious mutations. At age 18 years, the mean difference in body weight, body mass index (BMI) and fat mass was 17.76kg (95% CI: 9.41, 26.10), 4.84kg/m2 (95% CI: 2.19, 7.49) and 14.78kg (95% CI: 8.56, 20.99), respectively, in carriers of loss of function (LoF) mutations compared to non-LoF carriers. Carriage of LoF mutations increased adiposity from as early as 5 years. MC4R LoF was associated with an impact on BMI at age 18 years that was approximately double that of a genome-wide polygenic risk score (comparing the upper 10th and lower 90th percentile). An extrapolation of incidence for MC4R LoF mutations from this birth cohort suggests that up to ∼200,000 people in the UK are likely to carry such mutations. This frequency, combined with the substantial impact of these variants on adiposity, has implications for public health, and drug development.

Polygenic hereditary traits of young pigs and their association with the melanocortin receptor gene – 4 (MC4R)

The article presents the results of studies of fattening and meat qualities of young pigs of different genealogical lines of large white breed and genotypes by the gene of melanocortin receptor – 4 (MC4R). The research was conducted in “Druzhba-Kaznacheyivka” LLC, the genetics laboratory of the Institute of Pig Breeding and APV NAAS and the animal husbandry laboratory of the State Institution Institute of Grain Crops NAAS. The work was performed according to the research program of NAAS №30 “Innovative technologies of breeding, industrial and organic production of pig products” (“Pig Breeding”). DNA-typing of the melanocortin-4 receptor gene (MC4R) was performed by Kim K., Larsen N., Short T. et al. (2000). Evaluation of young pigs for fattening and meat qualities was carried out taking into account the following quantitative characteristics: the average daily increase in live weight during the period of control fattening, g; age of live weight 100 kg, days; fat thickness at the level of 6–7 thoracic vertebrae, mm; the length of the cooled carcass cm; the length of the bacon half of the cooled half-carcass, cm. The length of the cooled carcass was measured with a measuring tape from the edge of the fusion of the pubic bones to the anterior surface of the first cervical vertebra; the length of the bacon half of the cooled half-carcass - from the anterior edge of the pubic bone to the middle of the anterior edge of the first rib (Berezovsky, Khatko, 2005). Conditions for feeding and keeping young pigs of the experimental groups were identical and complied with zootechnical standards. Economic efficiency of use of animals of various genotypes (МС4RАА, МС4RАG) and biometric processing of the received data (Lakin, 1990). calculated according to generally accepted methods. It is established that young pigs of large white breed of controlled population at the age of reaching live weight of 100 kg exceed the minimum requirements of the elite class by 6.73, fat thickness at the level of 6–7 thoracic vertebrae – 30.84, length of chilled carcass – 3.52 %. Significant difference between animals of different genotypes by melanocortin 4 receptor gene (МС4RАА, МС4RАG) was established by the average daily gain of live weight during the control period of fattening, the age of reaching live weight of 100 kg, fat thickness at the level of 6–7 thoracic vertebrae, length half of the cooled half-carcass and a complex index of fattening and meat qualities (B. Tyler's index). Young pigs of large white breed line Kotilo UA 8819347 outperformed peers line Azuro UA 8800557 on average daily live weight gain during the control period of fattening by 5.29%, the age of 100 kg live weight – 3.29 %, fat thickness at the level of 6–7 breasts vertebrae – 7.14 %. The longer length of chilled carcass (by 1.13 %) and the length of bacon half of chilled half carcass (by 2.68 %) were characterized by animals of Azuro UA 8800557. The correlation coefficient between fattening and meat qualities in young pigs of large white breed of the controlled herd varies ranging from –0.865 (tr = 22.26, P < 0.001) to +0.913 (tr = 35.43, P < 0.001). The maximum increase in additional products was obtained from young pigs of the МС4RАG genotype (+2.57 %) and the genealogical line Kotilo UA 8819347 (+4.86 %), and its cost is +694.26 – 1312.88 UAH/head. in accordance.

Fattening and meat qualities of store pigs of large white breed of different intra-breed differentiation by melanocortin-4 receptor gene (MC4R)

The study presents the results of research on fattening and meat qualities of store pigs of large white breed of different intra-breeding differentiation by the gene of melanocortin-4 receptor (MC4R). The study calculated the economic efficiency of animals of different genotypes. The following fattening and meat qualities were evaluated: average daily increase in live weight during the period of control fattening, g; age of live weight 100 kg, days; fat thickness at the level of 6-7 thoracic vertebrae, mm; the length of the cooled carcass, cm; length of bacon half of chilled half-carcass, cm. It was established that store pigs of controlled population at the age of reaching live weight of 100 kg, fat thickness at the level of 6-7 thoracic vertebrae, and length of chilled carcass exceed the minimum requirements of the elite class by 13.69%. A significant difference between animals of different genotypes by the gene of the melanocortin-4 receptor (MC4RAA, MC4RAG) was established according to the average daily live weight gain during the control fattening period (4.24%, P <0.01), the age of reaching a live weight of 100 kg (2.18%, P <0,01), fat thickness at the level of 6–7 thoracic vertebrae (8,45%, P <0,05), length of chilled carcass (2,26%, P <0,001), length of bacon half of chilled half carcass (3.36%, P <0.001) and selection index (SI) (18.92%, P <0.05). Significant correlations in animals of different genotypes by the melanocortin-4 receptor gene (MC4RAA, MC4RAG) were identified regarding the following features: average daily live weight gain during the control period of fattening × age of 100 kg live weight (-0.475 – -0.853), average daily live weight for the period of control fattening × SI (+0.686 - +0.770), SI × age of reaching live weight 100 kg (+0.515 – -0.721), SI × fat thickness at the level of 6-7 thoracic vertebrae (-0.944 – -0.885), length of chilled carcass × length of bacon half of chilled carcass (+0.899 – +0.861). The maximum increase in additional products was obtained from the sale of young pigs by the gene for the melanocortin-4 receptor MC4RAG – +2.02%.

The Relationship between Selected CNR1, MC4R, LEP, FTO and VDR Gene Polymorphisms and Several Basic Toxicological Parameters Among Persons Occupationally Exposed to Arsenic, Cadmium and Lead

The purpose of this work was to assess the influence of selected CNR1, MC4R, LEP, FTO and VDR FOKI gene polymorphisms on blood and urine concentration markers of lead, cadmium and arsenic in a population directly exposed to these metals. Eighty-five people exposed to lead, arsenic and cadmium were qualified to take part in the study. Standard urine samples and 25 mL of venous blood from each worker were collected to assay basic laboratory and toxicological markers as well as selected single nucleotide polymorphisms (SNPs) within CNR1—cannabinoid receptor 1 gene (rs806368, rs806381, rs1049353, rs12720071), MC4R—melanocortin 4 receptor gene (rs17782313), LEP—leptin promoter gene (rs7799039), FTO—alpha-ketoglutarate-dependent dioxygenase gene (rs9939609) and VDR—vitamin D receptor (rs10735810) genes. It appeared that, except for the MC4R SNP, all the other polymorphisms were found to be associated with various laboratory parameters. Arsenic concentration in urine was associated with all four CNR1 and LEP SNPs, while cadmium concentration in blood was affected by the VDR polymorphism. Moreover, some significant relationships were also observed between CNR1 rs1049353 and FTO rs9939609 gene variants and markers of lead exposure. These results imply SNPs within genes coding for proteins involved in development of metabolic syndrome may be of prognostic value for persons directly exposed to lead, cadmium and arsenic.

Effect of MC4R gene polymorphism on food intake in adolescents with overweight and obesity

BACKGROUND: The melanocortin 4 receptor gene (MC4R) codes the receptor expressed in the hypothalamus and involved in the regulation of body mass and height. Data on the association of polymorphism MC4R rs17782313 with anthropometric parameters are contradictory. AIMS: to study the influence of the carrier of polymorphism MC4R rs17782313 on the anthropometric parameters in adolescents of different ethnic groups: caucasians and mongoloids living in the Siberia. MATERIALS AND METHODS: The study included 179 caucasian adolescents (by the example of russians, average age is 15.07 1.25 years) and 182 mongoloid adolescents (by the example of the buryats, the average age is 14.71 1.28 years), 89 and 92 adolescents were included in groups with overweight and obesity (standard deviation (SDS) BMI 1), in the control groups (SDS BMI from -1 to + 1) also 90 and 90 adolescents were included in the control groups (SDS BMI from -1 to + 1) (russian and buryat, respectively). Anthropometric measurements included height, weight with the calculation of BMI and SDS BMI, WC (waist circumference), HC (hip circumference ). Genotyping was performed by real-time PCR. Statistical analysis of the results of the study was carried out using the software STATISTICA 8.0. RESULTS: We showed no association of the risky C-allele of polymorphism rs17782313 with overweight and obesity in russian adolescents (22.5% vs 17.9% OR = 1.34 (p 0.05)) and in the buryat (29.8% vs 24.1%, OR = 1.43 (p 0.05)). It was revealed that adolescent carriers of the C-allele in buryat showed higher growth in both groups (control: 162.19 cm vs 157.26 cm (p = 0.019)), the main group: 165.24 cm vs 164.91 cm (p = 0.041)), as well as weight gain in the control group (52.29 kg vs 48.05 kg (p = 0.028)). CONCLUSIONS: Thus, the study revealed the relationship of MC4R rs17782313 polymorphism with height and weight in adolescents of buryat ethnic group.