ABSTRACT
Obesity is a state of chronic inflammation. Data on IGF system are often discrepant, and their relationships with mediators of inflammation are unknown. Furthermore, changes in thyroid function have been reported. We aimed at investigating the changes in these systems, and verify any relationships among cytokines, IGF system, thyroid function and insulin-insensitivity. Fifty obese pre-pubertal children, and 55 normal-weight subjects comparable for age and sex were enrolled. Serum IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, IL-6 and TNF-alpha were assayed. In obese children insulin, TSH and FT4 were measured also, and the HOMA-IR index was calculated. Increased IGF-II, IL-6 and TNF-alpha, and decreased IGFBP-1 and IGFBP-2 concentrations were found in obese compared to normal-weight children. The IGF-I/IGFBP-3 molar ratio was also reduced in the obese subjects. In the obese children with high HOMA-IR index, IGFBP-1 and -2 serum concentrations were significantly decreased compared with those with normal insulin sensitivity, and in the obese subjects with increased TSH, IGFBP-2 concentrations were lower, and IGFBP-3 levels were higher compared to their counterparts with normal TSH levels. Among the significant correlations, BMISDS was correlated with IGF-II, and TSH. IGF-II concentrations showed a positive relationship with IL-6. TSH was correlated with IGFBP-2 also. The data showed interactions among IL-6, IGF system, insulin sensitivity, and thyroid function with changes being related to the degree of obesity. Chronic inflammation in obese children was confirmed. Some of the changes in the IGF system could be a consequence of insulin resistance and could account also for later complications in obese subjects.
Subject(s)
Cytokines/blood , Inflammation Mediators/blood , Obesity/blood , Obesity/physiopathology , Puberty/blood , Somatomedins/metabolism , Thyroid Gland/physiopathology , Body Mass Index , Body Weight , Child , Female , Humans , Insulin Resistance , Insulin-Like Growth Factor Binding Protein 1/blood , Insulin-Like Growth Factor Binding Protein 2/blood , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor II/metabolism , Interleukin-6/blood , MaleABSTRACT
We followed-up, from pregnancy to birth, a group of newborns both IUGR and AGA and we aimed at establishing placental biochemical determinants of birth weight and length. Insulin, total and activated insulin receptor contents (IR), cortisol and IL-6 placental concentrations were assayed in 23 IUGR and 37 AGA subjects at birth, and a multiple regression model was designed and applied to assess the significant biochemical determinants of birth size. IL-6 and activated insulin receptor content were significantly increased in IUGR, whereas insulin, total insulin receptor content, and cortisol placental concentrations were similar in IUGR and AGA. Placental cortisol concentration was found to be significantly and negatively related with both birth length (0.778, P<0.001) and weight (0.508, P<0.008). A negative effect of IL-6 placental concentration was found on birth length (P<0.002). For the first time we provide evidence of a negative association of placental cortisol and IL-6 concentrations on birth size.
Subject(s)
Birth Weight , Body Height , Hydrocortisone/analysis , Insulin/analysis , Interleukin-6/analysis , Placenta/chemistry , Receptor, Insulin/analysis , Female , Fetal Growth Retardation/metabolism , Humans , Infant, Newborn , Male , Pilot Projects , Pregnancy , Regression AnalysisABSTRACT
We report the cloning of a novel gene, called Tramp, in the Xp/Yp PAR region that has a functional homologue on the Y chromosome and escapes X-inactivation. This gene encodes, within a single exon, a putative protein that has amino acid similarity with transposases of the Ac family. Flanking this gene we have identified putative terminal inverted repeats (TIRs) and a duplicate target site, suggesting that it may be an ancient transposable element. The nucleotide differences in these sites and the TIR-binding inactivity of the putative Tramp protein suggest that this element is not an autonomous transposon. In the human genome, the Tramp protein may be involved in the transposition of other transposable elements, like medium reiterated frequency repeats, or it could be specialized in the acquisition of a new cellular function.
Subject(s)
Transposases/genetics , Amino Acid Sequence , Animals , Base Sequence , Chromosome Mapping , Cloning, Molecular , DNA Primers/genetics , DNA Transposable Elements/genetics , DNA, Complementary/genetics , Dosage Compensation, Genetic , Female , Genome, Human , Humans , Hybrid Cells , In Vitro Techniques , Molecular Sequence Data , Sequence Homology, Amino Acid , Terminal Repeat Sequences , Y Chromosome/geneticsABSTRACT
We report the cloning of a novel Xp/Yp pseudoautosomal gene called PGPL , and demonstrate that PGPL , like other pseudoautosomal genes, escapes X inactivation and has a functional homologue on the Y chromosome. This gene is expressed in all the tissues examined and is highly conserved across several species. The PGPL gene encodes a protein of 442 amino acids and shows the consensus sequences of a series of motifs of the GTP-binding protein domain. Using fluorescence in situ hybridization analysis on normal males and on patients with rearrangements in the pseudoautosomal region, the gene was localized within 500 kb of the telomere. Further refinement using a cosmid contig of the region places this novel gene within 80-110 kb of the telomere, making this the most telomeric gene on the short arms of the sex chromosomes.
