Maternal pregestational BMI is associated with methylation of the PPARGC1A promoter in newborns.

We explored peroxisome proliferator-activated receptor-gamma co-activator 1alpha gene (PPARGC1A), peroxisome proliferator-activated receptor-gamma gene (PPARG), and transcription factor A mitochondrial gene (Tfam) promoter DNA methylation in newborns between both extremes of abnormal fetal growth: Small (SGA) and large for gestational age (LGA) in relation to the mother's characteristics. We further sought for the association of rs9930506 variant at FTO gene and the promoter patterns of DNA methylation in the aforementioned genes, in relation to the offspring's birth weight. In a cross-sectional study, 88 healthy pregnant women and their babies were included. According to the offspring birth weight, there were 57 newborns with appropriate weight for gestational age (AGA), 17 SGA, and 14 LGA. After bisulphite treatment of umbilical cord genomic DNA, a real-time methylation-specific PCR was used to determine the promoter methylation status in selected CpGs. Promoter methylated DNA/unmethylated DNA ratio, expressed as mean +/- s.e., was 0.82 +/- 0.15 (45% of alleles) for PPARGC1A, and 0.0044 +/- 0.0006 (0.4% of alleles) for Tfam. PPARG promoter was almost 100% methylated in all samples. In univariate analysis, there was no association among characteristics of the newborn and gene promoter methylation. None of the maternal features were related with the status of promoter methylation, except for a positive correlation between maternal BMI and PPARGC1A promoter methylation in umbilical cord (Pearson correlation coefficient r = 0.41, P = 0.0007). Finally, FTO rs9930506 AA homozygous in the LGA group showed decreased levels of methylated PPARGC1A in comparison with AG + GG genotypes and AGA and SGA infants. In conclusion, our findings suggest a potential role of promoter PPARGC1A methylation in metabolic programming.

Short allele of serotonin transporter gene promoter is a risk factor for obesity in adolescents.

Obesity and hypertension are increasing medical problems in adolescents. Serotonin transporter (5-HTT) is involved in mood and eating disturbances. Encoded by the gene SLC6A4, the promoter shows functional insertion/deletion alleles: long (L) and short (S). Because individuals who are carriers for the short version are known to be at risk for higher levels of anxiety, we hypothesized that this variant may be associated with overweight. Data and blood samples were collected from 172 adolescents out of a cross-sectional, population-based study of 934 high school students. To replicate the findings, we also included 119 outpatients from the Nutrition and Diabetes Section of the Children's County Hospital. We found that the S allele was associated with overweight (BMI > 85th percentile), being a risk factor for overweight independently of sex, age, and hypertension [odds ratio (OR): 1.85; 95% confidence interval (CI): 1.13, 3.05; p < 0.02]. Additionally, in the outpatient study, compared with the homozygous LL subjects, S allele carriers showed a higher BMI z-score (1.47 +/- 1.09 vs. 0.51 +/- 1.4; p < 0.002) and were more frequent in overweight children. In conclusion, the S allele of the SLC6A4 promoter variant is associated with overweight being an independent genetic risk factor for obesity.

Mitochondrial DNA depletion in small- and large-for-gestational-age newborns.

OBJECTIVE: To investigate whether mitochondrial DNA (mtDNA) content may be associated with clinical features, anthropometric variables, and laboratory findings in both extremes of abnormal fetal growth: small and large size for gestational age. RESEARCH METHODS AND PROCEDURES: Eighty-eight pregnant women and their infants were included in a cross-sectional study. According to the offspring birthweight, normalized by sex and gestational age, there were 57 newborns with appropriate weight for gestational age (AGA) and 31 with abnormal weight for gestational age: 17 small for gestational age (SGA) and 14 large for gestational age (LGA). mtDNA quantification using nuclear DNA as a reference was measured by a real-time quantitative polymerase chain reaction method. RESULTS: The mothers' pregestational BMI was associated with the weight of their offspring: SGA infants had lean mothers (BMI, 21.4 +/- 0.7), and LGA infants had overweight mothers (BMI, 26.7 +/- 1.4) in comparison with AGA infants (BMI, 23.0 +/- 0.7) (p < 0.003). Newborn leptin levels were associated with birthweight after adjustment for sex and gestational age (SGA, 7.0 +/- 1.1 ng/mL; AGA, 15.2 +/- 1.6 ng/mL; and LGA, 25.6 +/- 4.1 ng/mL) (p < 0.002). Conversely, mtDNA/nuclear DNA ratio was significantly lower in both extremes of abnormal fetal growth, SGA (18 +/- 6) and LGA (9 +/- 2), at birth in comparison to AGA-weight infants (28 +/- 4) (p < 0.03). DISCUSSION: Our findings show that mtDNA content is decreased in newborns with abnormal weight in comparison with AGA infants. On the basis of a cumulative body of evidence, we speculate that mtDNA depletion is one of the putative links between abnormal fetal growth and metabolic and cardiovascular complications in later life.

Non-invasive routes for insulin administration: current state and perspectives.

Diabetes mellitus is a chronic disease that usually requires multiple insulin injections to achieve adequate glycaemic control. This represents a major cause of reduced compliance to treatment. Consequently, other routes for insulin administration have been explored. During recent years, much progress in the development of inhaled insulin has been made. Inhaled insulin has shown favourable properties, such as a rapid onset of action, improved bioavailability and good tolerability; thereby providing satisfaction and ease of administration. However, long-term safety of inhaled insulin needs to be assessed, and the cost would be higher than injectable insulin. Nasal, oral and transdermal insulins are undergoing early phases of pharmacological development. The purpose of this review is to describe the latest developments in the area of non-invasive routes for insulin delivery.