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MON-092 Role of Genetic Variants of NNMT rs694539 and rs1941404, FTO rs1421085 and Irx3 rs3751723 Polymorphisms on Resting Energy Expenditure and BMI

ABSTRACT: Abstract In obesity the NNMTrs694539 polymorphism associates with cardiovascular damage and nonalcoholic steatohepatitis, and rs1941404 with hyperlipidemia.NNMT (Nicotidamide-N-methyltransferase) is a regulator of adiposity and energy expenditure correlating with BMIand energy metabolism. FTOrs1421085 polymorphism regulates food behavior, and IRX3rs3751723 is associated with obesity risk.Resting energy expenditure (REE) is an essential component of obesity. To evaluate the role of NNMTrs694539 and rs1941404,and FTOrs1421085 and IRX3rs3751723 polymorphisms on REEand BMI. We recruited 200 healthy subjects 30 to 50 years of age, 100 non-obese (BMI 18.5-29.5) and 100 obese (BMI ?30 kg/m2). and REE evaluated by indirect calorimetry. A fasting blood sample was obtained for metabolites and DNA extraction. Leptin and insulin were quantified. MNA-1 was measured by LC-MS. The NNMTrs694539, rs1941404, FTOrs1421085, and IRX3rs3751723 polymorphisms were genotyped by PCR-RFLP and Taqman allelic discrimination respectively. MNA-1 concentrations and REE were higher in obese subjects. REE correlated with BMI, (p < 0.00001), insulin (p=0.001) andHOMA-IR (p=0.0004). The plasma MNA-1 correlated negatively with HOMA-IR in obese subjects (p=0.042). The rs694539AA genotype frequency was significantly higher in lean subjects. The NNMTrs1941404, and IRX3 rs3751723 polymorphisms was not different in allelic or genotypes frequencies in both groups. The risk allele frequency of FTOrs1421085 was different between groups (p=0.049; OR=1.76). Carriers of one or two risk alleles had more weight 6 kg or 2 BMI units than subjects with WT genotype. Under recessive model carriers of rs694539 AA genotype had lower weight, BMI, and REE than those with GG and AG genotypes, andcarriers of rs1941404GG genotype had marginally higher BMI, leptin, and MNA. The TG haplotype of rs1421085 and rs3751723 were associated with BMI adjusted by gender and age (coefficient -3.41±1.41, p=0.017). REE and MNA-1 were significant higher in obese subjects. Carriers of rs694539 AA genotype had lower weight, BMI, REE. The risk allele frequency of FTOrs1421085 was marginally different (p=0.049; OR=1.76) among groups. The carriers of one or two risk allele had 6 kg and 2 BMI units more than wild type genotype subjects. TG haplotype of rs1421085 and rs3751723 was associated with BMI. Support: CONACYT, and CIFOREA-UG.

SUBMITTER: Banales Luna M

PROVIDER: S-EPMC6550987 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:There are significant variations in gestational weight gain, with many women gaining in excess of the Institute of Medicine guidelines. Unfortunately, efforts to improve appropriate gestational weight gain have had only limited success. To date, interventions have focused primarily on decreasing energy intake and/or increasing physical activity. Maternal resting energy expenditure, which comprises ?60% of total energy expenditure compared with the ?20% that comes from physical activity, may be an important consideration in understanding variations in gestational weight gain. OBJECTIVE:Our objective was to quantify the changes in resting energy expenditure during pregnancy and their relationship to gestational weight gain and body composition changes among healthy women. We hypothesized that greater gestational weight gain, and fat mass accrual in particular, are inversely related to variations in resting energy expenditure. STUDY DESIGN:We conducted a secondary analysis of a prospective cohort studied before conception and late pregnancy (34-36 weeks). Body composition (estimated using hydrodensitometry) and resting energy expenditure (estimated using indirect calorimetry) were measured. The relationship between the changes in resting energy expenditure and gestational weight gain and the change in fat mass and fat-free mass were quantified. Resting energy expenditure was expressed as kilocalories per kilogram of fat-free mass per day (kilocalories per kilogram of fat-free mass-1/day-1) and kilocalories per day. Correlations are reported as r. RESULTS:Among 51 women, preconception body mass index was 23.0 (4.7) kg/m2; gestational weight gain was 12.8 (4.7) kg. Preconception and late pregnancy resting energy expenditure (kilocalories per day) correlated positively with the change in fat-free mass (r = 0.37, P = .008; r = 0.51, P = .001). Late-pregnancy resting energy expenditure (kilocalories per kilogram of fat-free mass-1/day-1) was inversely associated with the change in fat mass (r = -0.34, P = .02) and gestational weight gain (r = -0.29, P = .04). From before pregnancy through late gestation, the increase in resting energy expenditure (kilocalories per day) correlated positively with the change in fat-free mass (r = 0.44, P = .002) and negatively with the change in fat mass (r = -0.27, P = .06). CONCLUSION:The change in resting energy expenditure from before conception through late gestation correlated positively with changes in fat-free mass but negatively with fat mass accrual. Women with smaller increases in resting energy expenditure across pregnancy had greater gestational weight gain, specifically more adipose tissue. These data suggest that resting energy expenditure is an important factor in gestational weight gain, particularly excess fat mass accrual. Future lifestyle intervention studies need to consider clinically feasible means of estimating resting energy expenditure and, in response, tailor nutrient intake and composition recommendations. Implementing and testing such interventions would be a novel approach to improve compliance with gestational weight gain guidelines.

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MON-092 Role of Genetic Variants of NNMT rs694539 and rs1941404, FTO rs1421085 and Irx3 rs3751723 Polymorphisms on Resting Energy Expenditure and BMI

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