Omega-3 fatty acids does not affect physical activity and body weight in primary school children - a double-blind randomized placebo-controlled trial.

It was hypothesized that supplementation of omega-3 fatty acids could increase physical activity (PA) levels, where traditional interventions often fail. The aim of this double-blind, randomized, placebo-controlled trail was to evaluate the effects of 15-week administration of omega-3 fatty acids on objectively measured PA and relative body weight in 8-9 year-old children. The children were randomly assigned to supplementation of omega-3 fatty acids or placebo. Primary outcome was change in PA counts per minute (cpm), and secondly change in body mass index standard deviation score (BMI SDS). Covariance models were applied adjusting for age, gender, weight status, PA and intervention season. Compliance was controlled for by analyzing fatty acid composition in plasma. The intention to treat population consisted of 362 children (omega-3 n = 177, placebo n = 185). No significant effects of omega-3 fatty acids on PA or relative body weight were observed. In covariance models no effects were observed by gender, weight status or change in PA (all p > 0.05), but inactive children increased their PA more than children classified as active at baseline (p < 0.05).

Infant growth is associated with parental education but not with parental adiposity - Early Stockholm Obesity Prevention Project.

AIM: To explore the simultaneous impact of parental adiposity and education level on infant growth from birth to 12 months, adjusting for known early-life risk factors for subsequent childhood obesity. METHODS: Baseline data for 197 one-year-old children and their parents, participating in a longitudinal obesity intervention, were used. Obesity risk groups, high/low, were defined based on parental body mass index (n = 144/53) and parental education (n = 57/139). Observational data on infant growth between 0 and 12 months were collected. The children's relative weight (body mass index standard deviation score) at 3, 6 and 12 months and rapid weight gain 0-6 months were analysed in regression models, with obesity risk as primary exposure variables, adjusting for gestational weight gain, birth weight, short exclusive breastfeeding and maternal smoking. RESULTS: Relative weight at 3, 6 and 12 months was associated with low parental education but not with parental adiposity. No significant associations were observed with rapid weight gain. None of the early-life factors could explain the association with parental education. CONCLUSION: Low parental education level is independently associated with infant growth, whereas parental obesity does not contribute to a higher weight or to rapid weight gain during the first year.

Associations between severity of obesity in childhood and adolescence, obesity onset and parental BMI: a longitudinal cohort study.

OBJECTIVE: To explore the relationship between severity of obesity at age 7 and age 15, age at onset of obesity, and parental body mass index (BMI) in obese children and adolescents. DESIGN: Longitudinal cohort study. SUBJECTS: Obese children (n = 231) and their parents (n = 462) from the Swedish National Childhood Obesity Centre. METHODS: Multivariate regression analyses were applied with severity of obesity (BMI standard deviation score (BMI SDS)) and onset of obesity as dependent variables. The effect of parental BMI was evaluated and in the final models adjusted for gender, parental education, age at onset of obesity, severity of obesity at age 7 and obesity treatment. RESULTS: For severity of obesity at age 7, a positive correlation with maternal BMI was indicated (P = 0.05). Severity of obesity at this age also showed a strong negative correlation with the age at onset of obesity. Severity of obesity at age 15 was significantly correlated with both maternal and paternal BMI (P < 0.01). In addition, BMI SDS at age 15 differed by gender (higher for boys) and was positively correlated with severity of obesity at age 7 and negatively correlated with treatment. Also, a negative correlation was indicated at this age for parental education. No correlation with age at onset was found at age 15. For age at onset of obesity there was no relevant correlation with parental BMI. Children within the highest tertile of the BMI SDS range were more likely to have two obese parents. CONCLUSION: The impact of parental BMI on the severity of obesity in children is strengthened as the child grows into adolescence, whereas the age at onset is probably of less importance than previously thought. The influence of parental relative weight primarily affects the severity of childhood obesity and not the timing.

Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents.

BACKGROUND: The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits. RESULTS: We screened exons 3 and 4 including exon-intron boundaries in FTO in 48 obese children and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896+37A>G, c.896+117C>G and c.896+223A>G). We further genotyped c.896+223A>G in 962 subjects, 450 well-characterized obese children and adolescents and 512 adolescents with normal weight. Evidence for differences in genotype frequencies were not detected for the c.896+223A>G variant between extremely obese children and adolescents and normal weight adolescents (P=0.406, OR=1.154 (0.768-1.736)). Obese subjects with the GG genotype, however, had 30% increased fasting serum insulin levels (P=0.017) and increased degree of insulin resistance (P=0.025). There were in addition no differences in body mass index (BMI) or BMI standard deviation score (SDS) levels among the obese subjects according to genotype and the associations with insulin levels and insulin resistance remained significant when adjusting for BMI SDS. CONCLUSION: These findings suggest that this novel variant in FTO is affecting metabolic phenotypes such as insulin resistance, which are not mediated through differences in BMI levels.

Constitutive and inducible cytokine mRNA expression in the human mast cell line HMC-1.

The discovery that mast cells are a potential source of cytokines has suggested new ways in which mast cells can act in immunological and inflammatory responses. In this study we have used the HMC-1 cell line as a model for human mast cells to study the constitutive and inducible mRNA expression of interleukins, colony-stimulating factors, interferons, tumour necrosis factors alpha and beta, tumour growth factor beta and platelet-derived growth factor A and B. We found that HMC-1 cells constitutively expressed mRNA for TNF-alpha and TGF-beta, and a low level of M-CSF. After treatment with the phorbol ester TPA or the calcium ionophore ionomycin expression of several cytokines, i.e. IL-1 beta, IL-3, IL-6, GM-CSF, TNF-beta and PDGF-A, could be detected. Both TPA and ionomycin induced the same set of cytokines, but the effect of TPA was more prominent. The relative induction was calculated to be 70X for IL-1 beta and IL-3, 30X for GM-CSF and PDGF-A and 3 - 10X for IL-6, M-CSF and TNF-beta. This study shows that human mast cells have the capacity to express not only cytokines mediating an immune response but also cytokines affecting other cell types, e.g. fibroblasts and endothelial cells, involved in later steps of the inflammatory response.

Islet amyloid polypeptide (IAPP):cDNA cloning and identification of an amyloidogenic region associated with the species-specific occurrence of age-related diabetes mellitus.

We have cloned and sequenced a human islet amyloid polypeptide (IAPP) cDNA. A secretory 89 amino acid IAPP protein precursor is predicted from which the 37 amino acid IAPP molecule is formed by amino- and carboxyterminal proteolytic processing. The IAPP peptide is 43-46% identical in amino acid sequence to the two members of the calcitonin gene-related peptide (CGRP) family. Evolutionary conserved proteolytic processing sites indicate that similar proteases are involved in the maturation of IAPP and CGRP and that the IAPP amyloid polypeptide is identical to the normal proteolytic product of the IAPP precursor. A synthetic peptide corresponding to a carboxyteminal fragment of human IAPP is shown to spontaneously form amyloid-like fibrils in vitro. Antibodies against this peptide cross-react with IAPP from species that develop amyloid in pancreatic islets in conjunction with age-related diabetes mellitus (human, cat, racoon), but do not cross-react with IAPP from other tested species (mouse, rat, guinea pig, dog). Thus, a species-specific structural motif in the putative amyloidogenic region of IAPP is associated with both amyloid formation and the development of age-related diabetes mellitus. This provides a new molecular clue to the pathogenesis of this disease.

Sequence divergence in a specific region of islet amyloid polypeptide (IAPP) explains differences in islet amyloid formation between species.

Amyloid deposits in the islets of Langerhans occur in association with type 2 diabetes mellitus (DM) in humans and cats and consist of a 37-amino-acid polypeptide known as islet amyloid polypeptide (IAPP). In order to find an explanation for the situation that islet amyloid (IA) does not develop in common rodent species, we have deduced the amino acid sequence of the IAPP molecule in mouse, rat and hamster. We find that a specific region of the molecule diverges to a high degree. Synthetic peptides corresponding to this region of human and hamster IAPP were compared for their ability to form amyloid fibrils in vitro. Whereas the human peptide readily formed fibrils with amyloid character, the hamster peptide completely lacked this property. We suggest this to be a likely explanation for the differences in IA formation between humans and rodents and discuss our findings in relation to the type 2 DM syndrome.

Alternative splicing of the platelet-derived growth factor A-chain transcript occurs in normal as well as tumor cells and is conserved among mammalian species.

Using a polymerase chain reaction approach, we have analyzed the alternative usage of the platelet-derived growth factor A-chain exon 6 in mRNA from various cell types. The results show that this sequence is utilized in a small fraction of the mRNA molecules in normal as well as transformed cells and that this phenomenon is conserved among mammalian species.