Relationship of lactation, BMI, and rs12255372 TCF7L2 polymorphism on the conversion to type 2 diabetes mellitus in women with previous gestational diabetes.

Women with previous gestational diabetes mellitus (pGDM) have a high risk of developing postpartum type 2 diabetes mellitus (T2DM). This study aimed to analyze the relationship between lactation, BMI, and TCF7L2 polymorphisms in the conversion to T2DM in women with pGDM. One hundred and fifty-three women con pGDM were recruited from public hospitals of León Guanajuato México. Three groups: normal glucose tolerance (NGT), impaired glucose intolerance (IGT), and T2DM after the oral glucose tolerance test were formed. Metabolic and hormone variables were measured, and genotyping was made by PCR-RFLP. The questionnaire included data on lactation (yes/no), duration of lactation, and full lactation. After 35 (21-49) months from the last partum, 54% of women had an NGT, 30.7% IGT, and 15% T2DM. BMI and rs12255372 are associated with the risk of conversion to IGT and T2DM [OR = 1.07 (95% IC 1.0-1.14, p = .041; OR =2.14, 95% IC 1.01-4.55, p = .04 respectively), while the lactation shows a strong protective effects OR = 0.15 (95% IC 0.062-0.39, p = .00007), and an apparent interaction with rs12255372T decreasing the risk in carriers (OR =2.15; 95% IC 0.97-4.7, p = .05). BMI is an independent risk factor of IGT/T2DM development. The lactation shows a strong protective effect and a possible interaction with rs12255372 polymorphism.

Metabolic, hormonal characteristics and genetic variants of TCF7L2 associated with development of gestational diabetes mellitus in Mexican women.

BACKGROUND: Variation in TCF7L2 gene is associated with type 2 diabetes and with gestational diabetes mellitus in several populations, but there are no data in Mexican women with gestational diabetes mellitus. In this study, we examined metabolic and hormonal measurements as well as TCF7L2 genetic variants. METHODS: We selected 108 pregnant women with normal glucose tolerance and 90 with gestational diabetes mellitus according to 2010 American Diabetes Association criteria matched for gestational week. We collected data on blood pressure, body mass index (BMI) and concentrations of blood glucose, HbA1c , lipids profile, insulin and glucagon-like peptide-1 (GLP-1). The genotyping of rs7903146 and rs12255372 polymorphisms were made with polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Actual and pre-gestational BMI, fasting glucose and HbA1c were higher (p < 0.001), and high-density lipoprotein cholesterol was lower (p < 0.02) in gestational diabetes mellitus women than euglycemic women. No significant differences were found for lipids, insulin and homeostasis model assessment-insulin resistance. Gestational diabetes mellitus women had high GLP-1 levels (32 vs 24, p < 0.004) and decreased ß-cell function (266 vs 438, p < 0.001). The frequency of rs12255372 risk allele in gestational diabetes women was significantly higher than that in euglycemic women (χ² = 8.96; p < 0.003) and confers a risk for gestational diabetes mellitus (OR = 9.1, 95% CI 2.8-29, p < 0.0002; and OR = 4.3, 95% CI 1.6-11.4, p < 0.003 based on dominant and co-dominant model, respectively). The generalized linear model showed that low beta function, high pre-gestational BMI and rs12255372 risk allele are independently associated with gestational diabetes. CONCLUSIONS: The elevated GLP-1 levels in gestational diabetes women suggested some abnormality in insulin secretion. The low ß-cell function, high pre-gestational BMI and rs12255372 risk allele are risk factors independently associated with the development of gestational diabetes.

Interaction Effects of FTO and MC4R Polymorphisms on Total Body Weight Loss, Post-Surgery Weight, and Post-Body Mass Index after Bariatric Surgery.

Bariatric surgery (BS) is considered the most effective intervention for patients with severe obesity and is used to maintain long-term weight loss and glycemic control. The aim of this study was to analyze the effects of genotypes and haplotypes of the fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes on total body weight loss (TBWL), post-surgery weight, and post-BMI after bariatric surgery. We retrospectively selected 101 patients from Bajio High Specialty Regional Hospital, León Guanajuato, México, who underwent Roux-en-Y gastric bypass (RYGB) to determine their body mass index (BMI), blood pressure, biochemical characteristics, and comorbidities. Post-surgery, patients were referred for registered anthropometry and blood pressure. Glucose, lipid and hepatic profiles, and insulin, leptin, and ghrelin levels were measured, and rs9939609, rs9930506, and rs1421085 FTO and rs17782313 MC4R polymorphisms were genotyped. Six (4-8) years after BS, post-surgery weight was greater in carriers of the rs9939609 and rs1421085 risk genotypes. TBWL was lower for the rs9930506 and rs1421085 risk genotypes. Insulin and HOMA-IR were greater in patients with the three FTO polymorphisms. There were significant interaction effects of the rs9930506 and rs1421085 FTO risk genotypes on weight and BMI in response to BS. No association was found with the MC4R polymorphism. The genotypes and haplotypes of the FTO gene influence post-surgery weight, TBWL, insulin levels, and HOMA-IR.

Analysis of the contribution of FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes to obesity in Mexican children.

BACKGROUND: Recent genome wide association studies (GWAS) and previous positional linkage studies have identified more than 50 single nucleotide polymorphisms (SNPs) associated with obesity, mostly in Europeans. We aimed to assess the contribution of some of these SNPs to obesity risk and to the variation of related metabolic traits, in Mexican children. METHODS: The association of six European obesity-related SNPs in or near FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes with risk of obesity was tested in 1,463 school-aged Mexican children (N(cases) = 514; N(controls) = 949). We also assessed effects of these SNPs on the variation of body mass index (BMI), fasting serum insulin levels, fasting plasma glucose levels, total cholesterol and triglyceride levels, in a subset of 1,171 nonobese Mexican children. RESULTS: We found a significant effect of GNPDA2 rs10938397 on risk of obesity (odds ratio [OR] = 1.30; P = 1.34 × 10-3). Furthermore, we found nominal associations between obesity risk or BMI variation and the following SNPs: ENPP1 rs7754561, MC4R rs17782313 and NEGR1 rs2815752. Importantly, the at-risk alleles of both MC4R rs17782313 and NPC1 rs1805081 showed significant effect on increased fasting glucose levels (ß = 0.36 mmol/L; P = 1.47 × 10(-3)) and decreased fasting serum insulin levels (ß = -0.10 µU/mL; P = 1.21 × 10(-3)), respectively. CONCLUSION: Our present results suggest that some obesity-associated SNPs previously reported in Europeans also associate with risk of obesity, or metabolic quantitative traits, in Mexican children. Importantly, we found new associations between MC4R and fasting glucose levels, and between NPC1 and fasting insulin levels.

Analysis of Factors Associated with Outcomes of Bariatric Surgery: rs1800497 ANKK1, rs1799732 DRD2 Genetic Polymorphisms, Eating Behavior, Hedonic Hunger, and Depressive Symptoms.

INTRODUCTION: A therapeutic approach to severe obesity is bariatric surgery (BS), which is considered an effective intervention for ameliorating comorbidities such as T2DM, hypertension, dyslipidemia, and cardiovascular diseases. Some polymorphisms are considered markers for addictive disorders and hedonic hunger. We analyzed factors associated with the outcomes of BS, including rs1800497 ANKK1 and rs1799732 DRD2 polymorphisms, eating behavior, hedonic hunger, and depressive symptoms. METHODS: We retrospectively selected 101 patients who underwent BS and agreed to participate. The previous conditions to BS, such as body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and comorbidities, were registered; the scholarship value was evaluated as the total number of years of scholarly education. To evaluate the post-surgery conditions of the participants, we took blood samples, anthropometric measures, and 3 questionnaires to evaluate eating behavior (TFEQ-R18), hedonic hunger (PFS), and depressive symptoms (PHQ-9). The ANKK1 rs1800497 and rs1799732 DRD2 polymorphisms were genotyped. RESULTS: The median total weight loss (TWL) was 34.7 kg, with a BMI of 33.8 kg/m2, 6 (4-8) years after BS. The TWL was positively associated with the TFEQ-R18 score (p = 0.006) and negatively associated with triglycerides (p = 0.011). rs1800497 ANKK1 was associated with TFEQ-R18 (OR = 1.13 (1.02-1.25), p = 0.009). We also found a negative correlation of pre-surgery BMI with scholarship (r = - 0.27, p < 0.05). CONCLUSION: The patients showed an improvement in metabolic and anthropometric parameters post-surgery. Interestingly, the ANKK1 Taq1A polymorphism was associated with eating behavior and scholarship with pre-surgery BMI, which may be considered predictors of BS outcomes.

Executive functions and selective attention are favored in middle-aged healthy women carriers of the Val/Val genotype of the catechol-o-methyltransferase gene: a behavioral genetic study.

BACKGROUND: Cognitive deficits such as poor memory, the inability to concentrate, deficits in abstract reasoning, attention and set-shifting flexibility have been reported in middle-aged women. It has been suggested that cognitive decline may be due to several factors which include hormonal changes, individual differences, normal processes of aging and age-related changes in dopaminergic neurotransmission. Catechol-O-methyltransferase (COMT), a common functional polymorphism, has been related to executive performance in young healthy volunteers, old subjects and schizophrenia patients. The effect of this polymorphism on cognitive function in middle-aged healthy women is not well known. The aim of the current study was to investigate whether measures of executive function, sustained attention, selective attention and verbal fluency would be different depending on the COMT genotype and task demand. METHOD: We genotyped 74 middle-aged healthy women (48 to 65 years old) for the COMT Val158Met polymorphism. We analyzed the effects of this polymorphism on executive functions (Wisconsin Card Sorting Test), selective attention (Stroop test), sustained attention (Continuous Performance Test) and word generation (Verbal Fluency test), which are cognitive functions that involve the frontal lobe. RESULTS: There were 27 women with the Val/Val COMT genotype, 15 with the Met/Met genotype, and 32 with the Val/Met genotype. Women carriers of the Val/Val genotype performed better in executive functions, as indicated by a lower number of errors committed in comparison with the Met/Met or Val/Met groups. The correct responses on selective attention were higher in the Val/Val group, and the number of errors committed was higher in the Met/Met group during the incongruence trial in comparison with the Val/Val group. Performance on sustained attention and the number of words generated did not show significant differences between the three genotypes. CONCLUSION: These findings indicate that middle-aged women carriers of the Val158 allele, associated with high-activity COMT, showed significant advantage over Met allele in executive processes and cognitive flexibility. These results may help to explain, at least in part, individual differences in cognitive decline in middle-aged women with dopamine-related genes.

Analysis of the percentages of monocyte subsets and ILC2s, their relationships with metabolic variables and response to hypocaloric restriction in obesity.

PURPOSE: Obesity results from excess energy intake over expenditure and is characterized by chronic low-grade inflammation involving circulating monocytes (Mo) and group 2 innate lymphoid cells (ILC2s) imbalance. We analyzed circulating Mo subsets and ILC2s percentages and ß2-adrenergic receptor (ß2AR) expression in lean and obese subjects, and the possible effect of hypocaloric restriction on these innate immune cells. METHODS: In 139 individuals aged 45 to 57 years, classified in 74 lean individuals (>18.9kg/m2 BMI <24.9kg/m2) and 65 with obesity (n = 65), we collected fasting blood samples to detect Mo subsets, ILC2s number, and ß2AR expression by flow cytometry. Lipids, insulin, leptin, and acylated-ghrelin concentrations were quantified. Resting energy expenditure (REE) was estimated by indirect calorimetry. These measurements were repeated in obese subjects after 7-weeks of hypocaloric restriction. RESULTS: Non-classical monocytes (NCM) and ß2AR expression on intermediate Mo (IM) were increased in obese individuals (p<0.001, in both cases), whereas the percent of ILC2s was decreased (p<0.0001). Stepwise regression analysis showed significantly negative associations of ILC2s with caloric intake, ß2AR expression on IM with REE, but a positive relationship between NCM and HOMA-IR. Caloric restriction allowed a significant diminution of NCM and the ß2AR expression on IM, as well as, an increase in the percent of classical Mo (CM), and ILC2s. ΔREE was related to ΔCD16+/CD16- ratio. CONCLUSIONS: These findings show that in obesity occur changes in NCM, ILC2s and ß2AR expression, which contribute to the low-grade inflammation linked to obesity and might revert with caloric restriction.

Associations of nicotidamide-N-methyltransferase, FTO, and IRX3 genetic variants with body mass index and resting energy expenditure in Mexican subjects.

The enzyme nicotidamide-N-methyltransferase (NNMT) regulates adipose tissue energy expenditure through increasing nicotinamide adenosine dinucleotide (NAD+) content. NNMT methylates nicotinamide to N1-methylnicotidamide (MNA-1) using S-adenosyl methionine. The rs694539 NNMT polymorphism is associated with non-alcoholic steatohepatitis, and rs1941404 is associated with hyperlipidemia. The rs1421085 FTO is related to poor eating behaviors, and rs3751723 IRX3 is associated with obesity. To investigate the association of rs694539 and rs1941404 NNMT, rs140285 FTO and rs3751723 IRX3 polymorphisms with MNA-1 concentrations, resting energy expenditure (REE) and BMI, we included clinically healthy Mexican subjects 30 to 50 years old, 100 subjects (35 men/65 women) with BMI > 30 kg/m2 and 100 subjects (32 men/68 women) with BMI < 25 kg/m2. Glucose, lipid profile, insulin, leptin, acylated ghrelin, and MNA-1 (LC-MS) were quantified. Resting energy expenditure (REE) was estimated using indirect calorimetry with a Fitmate instrument. Genotyping was performed using PCR-RFLP, and allelic discrimination was examined using TaqMan probes. MNA-1 concentrations and REE were significantly higher in obese subjects. Subjects with the rs694539AA NNMT genotype (recessive model) had lower weight, BMI, and REE. BMI showed an association with HDL-C, triglycerides, MNA-1, acetylated ghrelin, leptin, insulin concentrations, HOMA-IR, REE, and rs1421085. Subjects with the TC or CC genotypes of rs1421085 FTO showed 6 kg and 2 units of BMI more than did those with the TT wild type. The CG of the rs1421085 and rs3751723 haplotypes was associated with BMI. These findings showed that BMI was strongly associated with REE, rs1421085 FTO and the CG rs1421085 FTO and rs3751723 IRX3 haplotypes. We used the GMDR approach in obesity phenotype to show the interaction of four SNPs and metabolic variables.

Expression of estrogen receptor alpha and beta in breast cancers of pre- and post-menopausal women.

Expression of estrogen receptors (ER) is clinically relevant in designing therapeutic strategies. The relative importance of the two types of estrogen receptors (ER-alpha and ER-beta) in human breast cancers in pre- and post-menopausal women has not been properly defined. To determine the possible association between the expression of estrogen receptor and serum estradiol levels in pre- and post-menopausal women with breast cancer. 44 patients with invasive ductal carcinoma of the breast were studied and a breast tissue biopsy was taken. ER-alpha and ER-beta were detected by immunocytochemistry. Serum levels of estradiol and estrone were measured by radioimmunoassay and FSH was measured using IRMA. We studied 21 pre- and 23 post-menopausal women with breast carcinoma. Examining the number of cases with tumors positive for ER, we found no differences in the frequency of ER-alpha between pre- and post-menopausal women, but ER-beta decreased marginally after menopause (p < 0.051). In cases with tumors positive for ER, the proportion of cells positive for ER-alpha was similar post-menopausally (53.95%) and pre-menopausally (57.21%), but for ER-beta the number of positive cells decreased significantly after menopause (p < 0.051). In pre-menopausal women there was a correlation between serum estradiol levels and ER-beta; in post-menopausal women there was a correlation between serum FSH levels and ER-alpha. These results indicate that estradiol levels in women with mammary carcinoma are related to ER-beta expression in the breast tumor tissue.

Factors associated with estrogen receptors-alpha (ER-alpha) and -beta (ER-beta) and progesterone receptor abundance in obese and non obese pre- and post-menopausal women.

There is scarce information about the factors associated with estrogen receptors (ER) at menopause. In 113 volunteers pre- and post-menopausal healthy women, grouped as with and without obesity, estrogen receptors-alpha and -beta, and progesterone receptor (PR) were measured by immunohistochemistry in skin punch biopsies obtained from the external gluteal area. In pre-menopausal women, biopsies and a blood sample were performed between days 7 and 14 of the cycle. Serum hormone levels were measured by immunoradiometric assay or radioimmunoassay. After menopause, ER and PR amounts decreased significantly. At pre-menopause, obese women had lower PR levels than non obese (P<.006). In the post-menopausal group, obese women showed higher ER-alpha (P<.03) and ER-beta (P<.02) levels than the non obese group. In the analysis of factors associated with the amount of steroid receptors for the total group, log[ER-alpha], log[ER-beta], and log[PR] were associated with age (P<.002, <.005, and <.004, respectively). The log[ER-alpha] was also associated with log[FSH] (P<.0008); meanwhile, the log[PR] showed a marginal correlation with log[FSH]. In pre-menopausal women no factor associated with any of the three receptors was found. In post-menopausal women log[ER-alpha] was associated with log[estrone] and log[DHEAS] (P<.003 and <.02, respectively). log[PR] was associated with BMI (P<.002), years since menopause (P<.05), and log[DHEAS] (P<.003). We concluded that ER and PR diminish sharply at post-menopause. At this stage the amount of receptors depends on several factors such as BMI, years since menopause, and androgen precursors.

[Symptomatic profile in peri and postmenopausal women]. / Perfil sintomático en mujeres peri y posmenopáusicas.

OBJECTIVE: To determine the symptoms that women refer during peri and postmenopause. PATIENTS AND METHOD: A cross-sectional study was carried out from April to December 2005; 500 women between 45 and 65 years old were included. We applied them the NR 1 questionnaire of symptoms for mature women. Data were obtained by means of a face-to-face interview. Results were analyzed through descriptive statistics, with percentage values, arithmetic mean and standard deviation. Differences between groups were evaluated with Student's T test, chi square test, and Fisher exact test. RESULTS: Perimenopausal women had higher levels of depression (p = 0.03). Postmenopausal women presented higher frequency of sleep disturbances (p = 0.003). We found that perimenopausal women had more night sweats (p = 0.005), excessive hot (p = 0.006), hot flashes (p = 0.001), headaches (p = 0.001), vaginal dryness (p = 0.03), and dyspareunia (p = 0.005). On the other hand, postmenopausal women presented higher frequency of changes in libido (p = 0.001). CONCLUSIONS: In general, perimenopausal women have more symptoms than posmenopausal women. It is advisable an exhaustive analysis of the perimenopausal women symptoms in order to offer them an integral substitutive treatment.

Effects of sleeve gastrectomy and rs9930506 FTO variants on angiopoietin/Tie-2 system in fat expansion and M1 macrophages recruitment in morbidly obese subjects.

Angiogenesis in inflammation are hallmarks for adipose tissue expansion in obesity. The role of angiopoietin/Tie-2 system in adipose tissue expansion and immune cell recruitment is unclear. We studied the effect of sleeve gastrectomy and the influence of FTO rs9930506 polymorphism on Tie-2, angiopoietin-1 and angiopoietin-2 expression in morbid obesity. Fifteen morbidly obese subjects (4 men and 11 women) aged 24-55 years were followed-up 3 and 6 months after sleeve gastrectomy. Serum sTie-2, angiopoietin-1, angiopoietin-2, and hypoxia-inducible factor-1α concentrations were determined by ELISA. Tie-2 and its ligands in visceral and subcutaneous adipose tissue were localized by immunohistochemistry. Tie-2 expression was measured by flow cytometry in circulating monocytes and infiltrated macrophages. Comparisons before and after sleeve gastrectomy were carried out using ANOVA for repeated measures. rs9930506FTO genotyping was performed by PCR-RFLP. Circulating sTie-2 and angiopoietin-2 were higher before sleeve gastrectomy. Tie-2 and angiopoietin-2 mRNA levels were higher in subcutaneous adipose tissue than visceral and both decreased after surgery. Monocytes and infiltrated macrophages showed a pro-inflammatory phenotype, with increased Tie-2 expression that decreased 3 and 6 months after sleeve gastrectomy. Baseline sTie-2 correlated inversely with adiponectin levels. At baseline the rs9930506FTO AG ó GG genotypes carriers had more 34 kg than genotype carriers of rs9930506 AA. Weight and body mass index decreased at 6 months. We found that angiopoietin/Tie-2 system is mainly expressed in subcutaneous adipose tissue, contributing to expandability, fat accumulation, and monocytes attachment in obesity. Bariatric surgery favorably modifies the pro-angiogenic profile, allowed a reduced angiogenic expression in the circulation and adipose tissue.

Obesity is associated with the Arg389Gly ADRB1 but not with the Trp64Arg ADRB3 polymorphism in children from San Luis PotosÍ and León, México.

This research was designed to analyze the possible associations of Arg389Gly ADRB1 and Trp64Arg ADRB3 polymorphisms in children with obesity. A cross-sectional study included 1,046 school-age Mexican participants (6-12 years old) from the cities of San Luis PotosÍ and León. Children were classified as non-obese or obese according to their body mass index (BMI) percentile; obese children had a BMI≥95th percentile for sex and age. Biochemical data were collected. Polymorphisms were detected using TaqMan qPCR assay. A logistic regression analysis was used to calculate the risk of obesity based on genotypes. Differences were found between groups where obese children had a significant increase in systolic and diastolic blood pressure, fasting plasma glucose, insulin, HOMA-IR, LDL-cholesterol, triglycerides, and lower HDL-cholesterol compared with the normal weight group (P<0.05). The distribution of allele frequency in the population was Arg= 87.4 and Gly= 12.6 (Hardy Weinberg equilibrium c2 = 3.16 , P = 0.07 ); Trp= 81.5 and Arg= 18.5 (Hardy Weinberg equilibrium c2 = 2.2, P = 0.14 ) for ADRB1 and ADRB3, respectively. Even though no different frequencies of Arg389Gly polymorphism between groups were found (P = 0.08), children carriers of one Gly389 ADRB1 allele had a risk for obesity of OR=1.40 (95%CI, 1.03-1.90, P = 0.03) after adjustment for age and gender. No other association was found for Trp64Arg ADRB3 polymorphism. Only the Arg389Gly ADRB1 polymorphism was associated with risk for obesity in Mexican children.

[Breast density and its association to polimorphism of the estrogen-receptor alpha gene Pvull and Xbal]. / Densidad mamaria y su asociación con el polimorfismo del gen del receptor de estrógenos alfa (REalpha) Pvull y Xbal.

OBJECTIVE: To study the influence of ER-alpha on mammographic density. MATERIAL AND METHODS: We selected 87 healthy women (age 49.8 +/- S.D. 6.12 years). We obtained the body mass index (BMI), and a fasting blood sample for hormone determinations and DNA extraction. ER-alpha genotyping was carried out by PCR and digestion with a Pvull and Xbal restriction endonucleases. Mammographic density was assigned by the radiologist used three categories of fatty, average and dense. RESULTS: Mammographic density was significantly associated with estradiol (p = 0.04), estrone (p = 0.04), and FSH (p = 0.02). The BMI was not associated with Pvull and Xbal genotypes and marginally with mammographic breast density (p = 0.06). CONCLUSIONS: We did not observe compelling evidence of an association between variant alleles of genotypes estrogen receptors alpha and breast density.

Modulation of the COMT Val(158)Met polymorphism on resting-state EEG power.

The catechol-O-methyltransferase (COMT) Val(158)Met polymorphism impacts cortical dopamine (DA) levels and may influence cortical electrical activity in the human brain. This study investigated whether COMT genotype influences resting-state electroencephalogram (EEG) power in the frontal, parietal and midline regions in healthy volunteers. EEG recordings were conducted in the resting-state in 13 postmenopausal healthy woman carriers of the Val/Val genotype and 11 with the Met/Met genotype. The resting EEG spectral absolute power in the frontal (F3, F4, F7, F8, FC3 and FC4), parietal (CP3, CP4, P3 and P4) and midline (Fz, FCz, Cz, CPz, Pz and Oz) was analyzed during the eyes-open and eyes-closed conditions. The frequency bands considered were the delta, theta, alpha1, alpha2, beta1 and beta2. EEG data of the Val/Val and Met/Met genotypes, brain regions and conditions were analyzed using a general linear model analysis. In the individuals with the Met/Met genotype, delta activity was increased in the eyes-closed condition, theta activity was increased in the eyes-closed and in the eyes-open conditions, and alpha1 band, alpha2 band and beta1band activity was increased in the eyes-closed condition. A significant interaction between COMT genotypes and spectral bands was observed. Met homozygote individuals exhibited more delta, theta and beta1 activity than individuals with the Val/Val genotype. No significant interaction between COMT genotypes and the resting-state EEG regional power and conditions were observed for the three brain regions studied. Our findings indicate that the COMT Val(158)Met polymorphism does not directly impact resting-state EEG regional power, but instead suggest that COMT genotype can modulate resting-state EEG spectral power in postmenopausal healthy women.

Dietary restriction in obese children and its relation with eating behavior, fibroblast growth factor 21 and leptin: a prospective clinical intervention study.

BACKGROUND: Obesity is significant problem involving eating behavior and peripheral metabolic conditions. The effect of carbohydrate and fat restriction on appetite regulation, fibroblast growth factor 21 (FGF21) and leptin in children has not been defined. Our objective was to compare the effect of both diets. METHODS: One hundred and twenty children with body mass index (BMI) higher than the equivalent of 30 kg/m(2) for an adult, as corrected for gender and age were randomly assigned to (n = 60) a low-carbohydrate (L-CHO) diet or (n = 60) a low-fat (L-F) diet for 2 months. Fifty-three (88.3 %) subjects on the low-carbohydrate-diet and 45 (75 %) on the low-fat diet completed the study. Anthropometric measures, leptin and FGF21 levels were measured before and after the intervention. Comparison of the data for both of the diet groups was carried out using the t-test for independent variables. Intragroup comparisons before and after of each of the dietary treatments were performed using ANOVA for repeated measures. Factors associated with FGF21, leptin levels and satiety, were analyzed by multiple regression. RESULTS: After both of the diets, weight, leptin, food responsiveness, and enjoyment of food significantly decreased and high density lipoprotein cholesterol (HDL) increased, but FGF21 decreased. Before and after both of the interventions FGF21 was associated with triglycerides. Before the diet, satiety was associated with lower screen time (p < 0.04) and insulin levels (p < 0.05). CONCLUSIONS: Both dietary restrictions improved the metabolic and hormonal parameters of obese children. FGF21 is an indicator of a beneficial metabolic response in younger children. After 2 months an adaptation of the eating behavior to food restriction was observed.

Circulating profiling reveals the effect of a polyunsaturated fatty acid-enriched diet on common microRNAs.

BACKGROUND: Consumption of long-chain polyunsaturated fatty acids (PUFAs), which are abundant in seafood and nuts, ameliorates components of the metabolic syndrome. Circulating microRNAs (miRNAs) have demonstrated to be valuable biomarkers of metabolic diseases. Here, we investigated whether a sustained nuts-enriched diet can lead to changes in circulating miRNAs, in parallel to the dietary modification of fatty acids (FAs). METHODS AND RESULTS: The profile of 192 common miRNAs was assessed (TaqMan low-density arrays) in plasma from 10 healthy women before and after an 8-week trial with a normocaloric diet enriched with PUFAs (30 g/day of almonds and walnuts). The most relevant miRNAs were validated in an extended sample of 30 participants (8 men and 22 women). Adiponectin was measured by immunoassay and FAs by gas liquid chromatography coupled to mass spectrometry. The percentage of both ω-3 (P=.01) and ω-6 (P=.029) PUFAs of dietary origin (as inferred from plasma FA concentrations) increased, whereas saturated FAs decreased (P=.0008). Concomitantly with changes in circulating FAs, several miRNAs were modified by treatment, including decreased miR-328, miR-330-3p, miR-221 and miR-125a-5p, and increased miR-192, miR-486-5p, miR-19b, miR-106a, miR-769-5p, miR-130b and miR-18a. Interestingly, miR-106a variations in plasma correlated with changes in PUFAs, while miR-130b (r=0.58, P=.003) and miR-221 (r=0.46, P=.03) reflected changes in C-reactive protein. The dietary modulation of miR-125a-5p mirrored changes in fasting triglycerides (r=-0.44, P=.019) and increased adiponectin (r=0.43, P=.026). CONCLUSION: Dietary FAs (as inferred from plasma FA concentration) are linked to changes in circulating miRNAs, which may be modified by a PUFAs-enriched diet.

Protective effect of DRB1 locus against type 2 diabetes mellitus in Mexican Mestizos.

The aim of the study was to investigate the participation of human leukocyte antigen (HLA) class II alleles in the expression of type 2 diabetic and in nondiabetic subjects with and without family history of diabetes. The purpose was to evaluate any HLA association and to look for different patterns of insulin resistance and insulin secretion, comparing subjects with a low probability of developing diabetes, as a result of their family history. We recruited 87 healthy subjects without family history of diabetes, 48 healthy subjects with family history, and 47 type 2 diabetic patients. All of them were Mexican Mestizos of central Mexico. Using a standard 75-g oral glucose tolerance test, insulin resistance was determined and insulin secretion was assessed with the HOMA model. DRB1, DQA1 and DQB1 alleles were typed using polymerase chain reaction-sequence-specific oligonucleotide probe (PCR-SSOP) and sequence specific primers (PCR-SSP). Nondiabetic subjects had similar HOMA-IR and DeltaI 30/DeltaG 30 index (HOMA). A significant decreased frequency of DRB1*0403 (p = 0.01; odds ratio [OR] = 0.20) was demonstrated in type 2 diabetic patients, and DRB1*0701 (p = 0.02; OR = 0.17) in nondiabetics with family history of diabetes. These alleles associated with protection against type 2 diabetes, share glutamic acid at position-74 and were previously demonstrated to contribute to protection against type I diabetes.

Sympathetic activity and response to ACE inhibitor (enalapril) in normotensive obese and non-obese subjects.

BACKGROUND: Angiotensinogen has been proposed as a possible link between obesity and hypertension because the adipocyte produces angiotensinogen and contains the enzymes required for its conversion. Moreover, sympathetic overactivity has been reported in obese subjects. The aim of this study was to compare heart sympathetic activation and serum angiotensinogen levels in obese and non-obese normotensive subjects, their relationship, and the effect of a drug that modifies the renin-angiotensin system. METHODS: Serum angiotensinogen, leptin, lipids, glucose, and insulin levels were measured and 24-h electrocardiograph monitoring was carried out in 41 (20 non-obese and 21 obese) volunteers before and after administration of 5 mg enalapril twice/day for 7 days. RESULTS: Obese subjects had higher values than non-obese subjects for % body fat (35.1+/-4.6 vs. 30.5+/-5.2; p=0.005), triglycerides (1.93+/-0.9 vs. 1.25+/-0.7 g/L, p=0.002), insulin (114.8+/-82.5 vs. 45.9+/-22.2 pmol/L), leptin (31.4+/-20.4 vs. 14.1+/-11.2 ng/mL, p=0.002), and LF/HFn index (4.3+/-2.9 vs. 2.2+/-1.3, p<0.005). Enalapril increased angiotensinogen levels only in the non-obese group (4.2+/-3.9 vs. 9.7+/-5.4 ng/mL, p=0.001) and diminished the LF/HFn index (4.3+/-2.9 vs. 3.0+/-1.4, p=0.007) in the group of obese subjects. There was no association between angiotensinogen levels and sympathetic activity. CONCLUSIONS: Higher level of sympathetic activity was found in normotensive obese as compared with non-obese subjects. Enalapril treatment reduced heart sympathetic activity in obese subjects but did not change angiotensinogen levels.

The relationship of estrogen receptor-alpha polymorphism with symptoms and other characteristics in post-menopausal women.

OBJECTIVES: To study the influence of the estrogen receptor-alpha (ER-alpha) genotypes (PvuII and XbaI polymorphisms) on symptoms and bone density. METHODS: We recruited 177 post-menopausal women to register hot flashes, vaginal dryness, depression, anxiety, sleep alterations, and serum hormones (FSH, LH, estrone, and estradiol). Bone mineral density (BMD) was measured with a radiographic method, correcting with an external reference. ER-alpha genotyping was carried out by PCR. RESULTS: Scores for vaginal dryness were lower for the xx (P = 0.003), and pp genotypes (P = 0.006). Hot flashes were lower for the Pp (P = 0.006) genotype. FSH circulating levels were lower for Xx genotype (P = 0.036). The factors associated with BMD were estrone (P > 0.000001), estradiol (P = 0.0035) and XbaI (P = 0.035). Vaginal dryness, was associated with PvuII and XbaI polymorphisms (P = 0.037 and P = 0.039). Depression was associated with log(estrone) (P = 0.011), schooling (negatively, P = 0.012), and marginally with BMI (P = 0.066). Sleep alterations correlated with log(estrone) (P = 0.014) and marginally with years since menopause (P = 0.046). Anxiety correlated with schooling (negatively, P = 0.006) and age (p = 0.015), and hot flashes with schooling (negatively, P = 0.014). BMD was associated with log(estrone) (p < 0.000001), estradiol (negatively, P = 0.0036), and marginally with XbaI (P = 0.036). CONCLUSIONS: In post-menopausal women, the ER-alpha polymorphism was associated with vaginal dryness, and hot flashes but not with other physical or emotional symptoms. Extraglandular estrogen production, and diverse molecular factors related to estrogen action may play an important role in this process.