Administration of glucocorticoid, estrogen, and progesterone is followed by changes in human adipose tissue distribution, morphology, and function. Therefore, specific receptors for these hormones were determined in different regions of human adipose tissue using ligand techniques, with separation of bound and free hormone by chromatography, absorption techniques, or isoelectric focusing, as well as protein quantitation with monoclonal antibodies against human estrogen and progesterone receptors. Furthermore, mRNAs were measured by solubilization hybridization technique with glucocorticoid, estrogen, and progesterone receptor cRNA probes for human receptors. Saturable specific cytosolic glucocorticoid binding was found. Quantitative analyses indicated more binding sites and mRNAs in intraabdominal than sc adipose tissue samples. In contrast, neither specific estrogen or progesterone binding, cytosolic or nuclear receptor protein, nor mRNAs for these receptors could be identified in abdominal, femoral, or omental adipose tissues. Parallel control experiments confirmed the presence of both estrogen and progesterone receptors in rat adipose tissues. It was concluded that while glucocorticoid receptors are clearly present in human adipose tissues, female sex hormone receptors are not present in quantities detectable with presently available methods. Effects of these hormones on human adipose tissue might, therefore, be mediated via a minute nondetectable quantity of receptors, the glucocorticoid receptor, or indirect mechanisms.

Aims/hypothesis: The aim of our study was to test the hypothesis that HLA genotypes conferring risk of diabetes, cord blood autoantibodies, or both are associated with increased birthweight. Methods: HLA genotypes were determined in dried blood spots of cord blood from a total of 16,709 children born to healthy mothers in the Diabetes Prediction in Skåne (DiPiS) study, a population-based observational clinical investigation of newborn children. Children born to mothers with diabetes or gestational diabetes were excluded. Autoantibodies to glutamic acid decarboxylase (GAD65Ab) and insulinoma-associated protein 2 were determined in standard radioligand binding assays. Birthweight was adjusted for gestational age and divided into quartiles. The upper quartile was defined as high relative birthweight (HrBW) and the lower quartile as low relative birthweight (LrBW). Results: Genotypes conferring risk of type 1 diabetes were strongly associated with relative birthweight (rBW) (p=0.01). The high-risk HLA-DQ2/8, DQ8/0604 and DQ8/X genotypes were associated with HrBW (odds ratio [OR] [95% CI]=1.20 [1.08-1.33], p=0.0006). The HLA-DQB1*0603 allele, which is negatively associated with type 1 diabetes, was also associated with HrBW (p=0.025), confirming a previous report on DQB1*0603-linked HLA-DR13. GAD65Ab were negatively associated with HrBW (OR [95% CI]= 0.72 [0.56-0.93], p=0.01). Regression analysis showed that the HLA-associated increase in rBW was independent of confounding factors. Conclusions/interpretation: HLA genotypes may be associated with intrauterine growth independent of type 1 diabetes risk. The epidemiological observation that high birthweight is a risk factor for type 1 diabetes could possibly result from a moderating effect on intrauterine growth of HLA genotypes conferring a high risk of diabetes.

No abstract

Intake of fish oil reduces the risk of CHD and CHD deaths. Marine n-3 fatty acids (FA) are susceptible to oxidation, but to our knowledge, the health effects of intake of oxidised fish oil have not previously been investigated in human subjects. The aim of the present study was to investigate markers of oxidative stress, lipid peroxidation and inflammation, and the level of plasma n-3 FA after intake of oxidised fish oil. In a double-blinded randomised controlled study, healthy subjects (aged 18-50 years, n 54) were assigned into one of three groups receiving capsules containing either 8 g/d of fish oil (1·6 g/d EPA þ DHA; n 17), 8 g/d of oxidised fish oil (1·6 g/d EPA þ DHA; n 18) or 8 g/d of high-oleic sunflower oil (n 19). Fasting blood and morning spot urine samples were collected at weeks 0, 3 and 7. No significant changes between the different groups were observed with regard to urinary 8-iso-PGF 2a ; plasma levels of 4-hydroxy-2-hexenal, 4-hydroxy-2-nonenal and a-tocopherol; serum high sensitive C-reactive protein; or activity of antioxidant enzymes in erythrocytes. A significant increase in plasma level of EPA þ DHA was observed in both fish oil groups, but no significant difference was observed between the fish oil groups. No changes in a variety of in vivo markers of oxidative stress, lipid peroxidation or inflammation were observed after daily intake of oxidised fish oil for 3 or 7 weeks, indicating that intake of oxidised fish oil may not have unfavourable short-term effects in healthy human subjects.