Resistin, an adipocyte secreted factor, has been suggested to link obesity with type 2 diabetes in rodent models, but its relevance to human diabetes remains uncertain. Although previous studies have suggested a role for this adipocytokine as a pathogenic factor, its functional effects, regulation by insulin, and alteration of serum resistin concentration by diabetes status remain to be elucidated. Therefore, the aims of this study were to analyze serum resistin concentrations in type 2 diabetic subjects; to determine the in vitro effects of insulin and rosiglitazone (RSG) on the regulation of resistin, and to examine the functional effects of recombinant human resistin on glucose and lipid metabolism in vitro. Serum concentrations of resistin were analyzed in 45 type 2 diabetic subjects and 34 nondiabetic subjects. Subcutaneous human adipocytes were incubated in vitro with insulin, RSG, and insulin in combination with RSG to examine effects on resistin secretion. Serum resistin was increased by approximately 20% in type 2 diabetic subjects compared with nondiabetic subjects (P = 0.004) correlating with C-reactive protein. No other parameters, including adiposity and fasting insulin levels, correlated with serum resistin in this cohort. However, in vitro, insulin stimulated resistin protein secretion in a concentration-dependent manner in adipocytes [control, 1215 +/- 87 pg/ml (mean +/- SEM); 1 nM insulin, 1414.0 +/- 89 pg/ml; 1 microM insulin, 1797 +/- 107 pg/ml (P < 0.001)]. RSG (10 nM) reduced the insulin-mediated rise in resistin protein secretion (1 nM insulin plus RSG, 971 +/- 35 pg/ml; insulin, 1 microM insulin plus RSG, 1019 +/- 28 pg/ml; P < 0.01 vs. insulin alone). Glucose uptake was reduced after treatment with 10 ng/ml recombinant resistin and higher concentrations (P < 0.05). Our in vitro studies demonstrated a small, but significant, reduction in glucose uptake with human recombinant resistin in differentiated preadipocytes. In human abdominal sc adipocytes, RSG blocks the insulin-mediated release of resistin secretion in vitro. In conclusion, elevated serum resistin in human diabetes reflects the subclinical inflammation prevalent in type 2 diabetes. Our in vitro studies suggest a modest effect of resistin in reducing glucose uptake, and suppression of resistin expression may contribute to the insulin-sensitizing and glucose-lowering actions of the thiazolidinediones.

The term intrauterine growth restriction (IUGR) is assigned to newborns with a birth weight and/or birth length below the 10th percentile for their gestational age and whose abdominal circumference is below the 2.5th percentile with pathologic restriction of fetal growth. IUGR is usually due to maternal, fetal, or placental factors. However, many IUGR cases have unknown underlying cause. Recent studies focus on new factors that can influence fetal development and birth outcome like the timing and the type of fetal nutrition, maternal psychosocial stress and personality variables, 11beta-hydroxysteroid dehydrogenase type 2 placental activity, the activity of the neuroendocrine system that mediates the effects of psychosocial stress, and the role of proinflammatory cytokines and of oxidative stress. Data have shown that IUGR is associated with a late life increased prevalence of metabolic syndrome, a condition associating obesity with hypertension, type 2 diabetes mellitus (DM2), and cardiovascular disease. Recent data demonstrated that the diabetes-associated mortality appears to be disproportionately concentrated among individuals of abnormal birth weight.

The link between sleep duration and obesity has been well established in adults, but several epidemiological studies revealed inconsistent findings in adolescents and younger children. This study aimed to investigate the relationship between sleep length and obesity in Saudi students. A total of 5,877 Saudi students, boys (55.2%) and girls (44.8%), aged between 10 and 19 years were randomly selected from elementary, intermediate, and secondary schools in different regions of Riyadh. A questionnaire on sleep behaviors was given. Anthropometry included BMI and waist and hip circumferences. Sleeping ≤7 h significantly increased the risk of obesity in both boys and girls (all age categories) (odds ratio = 1.25–1.38, 95% confidence intervals = 1.02–1.89). Overall prevalence of overweight and obese were higher among those sleeping intermittently (18.68%) than those sleeping continuously (14.5%) (P = 0.024). Short sleep duration and poor sleep quality are significantly associated with obesity among Arab youth. Further studies need to employ more objective measures of sleep, such as actigraphy, and examine the mechanism of these associations.

In postmenopausal PCOS women, ACTH and cortisol responses to CRH are normal. Androgen levels at baseline are higher in PCOS than control women and remain increased after ACTH stimulation. The dexamethasone suppression results in postmenopausal PCOS women suggest that DHEAS and total T are partially of adrenal origin. Although the ovarian contribution was not fully assessed, increased Δ(4)A production suggests that the ovary also contributes to hyperandrogenism in postmenopausal PCOS women. In conclusion, postmenopausal PCOS women are exposed to higher adrenal and ovarian androgen levels than non-PCOS women.

In all subjects, leptin and adiponectin predict negatively and positively anti-oxidation, respectively, while high sensitivity IL-6 predicts positively and negatively pro- and anti-oxidation, respectively. High-sensitivity C-reactive protein is increased and negatively associated with anti-oxidation in pre-pubertal obese boys, suggesting that childhood obesity is associated with aseptic inflammation and oxidative stress.

Glucocorticoids and androgens have both been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD); androgen deficiency in males, androgen excess in females, and glucocorticoid excess in both sexes are associated with NAFLD. Glucocorticoid and androgen action are regulated at a prereceptor level by the enzyme 5α-reductase type 2 (SRD5A2), which inactivates glucocorticoids to their dihydrometabolites and converts T to DHT. We have therefore explored the role of androgens and glucocorticoids and their metabolism by SRD5A2 upon lipid homeostasis in human hepatocytes. In both primary human hepatocytes and human hepatoma cell lines, glucocorticoids decreased de novo lipogenesis in a dose-dependent manner. Whereas androgen treatment (T and DHT) increased lipogenesis in cell lines and in primary cultures of human hepatocytes from female donors, it was without effect in primary hepatocyte cultures from men. SRD5A2 overexpression reduced the effects of cortisol to suppress lipogenesis and this effect was lost following transfection with an inactive mutant construct. Conversely, pharmacological inhibition using the 5α-reductase inhibitors finasteride and dutasteride augmented cortisol action. We have demonstrated that manipulation of SRD5A2 activity can regulate lipogenesis in human hepatocytes in vitro. This may have significant clinical implications for those patients prescribed 5α-reductase inhibitors, in particular augmenting the actions of glucocorticoids to modulate hepatic lipid flux.

Background:Oxidative stress is associated with obesity while the evidence for the role of GH in pro-and antioxidation is inconclusive. This study investigates the relationships between growth hormone (GH), pro-and antioxidation in relation to obesity and puberty before and after an acute bout of exercise. Methods: In this case-control study, 76 healthy normalweight and obese, prepubertal and pubertal boys underwent a blood sampling before and immediately after an aerobic exercise bout until exhaustion at 70% maximal oxygen consumption. Markers of prooxidation (thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PCs)) and antioxidation (glutathione (GSH), oxidized glutathione disulfide (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPX), catalase, and total antioxidant capacity (TAC)) and hormones (GH, insulinlike growth factor (IGF)-1, IGF-BP-3, luteinizing hormone, follicle-stimulating hormone, and testosterone) were measured. results: Baseline and postexercise TBARS and PCs were greater, while baseline GSH, GSH/GSSG ratio, GPX, and TAC were lower in obese than that in normal-weight participants. In all participants, waist was the best negative and positive predictor for postexercise GPX and TBARS, respectively. Baseline TAC was greater in pubertal than that in pre-pubertal participants. In all participants, baseline GH was the best negative predictor for postexercise PCs. Significant positive linear correlation exists between the exercise-associated GH, and GSSG increases in pubertal normal-weight boys. conclusions: Higher prooxidation and lower antioxidation were observed in obese boys, while antioxidation improves with puberty and postexercise, paralleling GH accentuated secretion.o xidative stress defines a state of imbalance between proand antioxidation within the cell (1). Prooxidation refers to mitochondrial and nonmitochondrial mechanisms, which generate reactive oxygen and nitrogen species (RONS), whereas antioxidation refers to the adaptive activation of enzymatic and/ or nonenzymatic mechanisms, which scavenge prooxidants and their products within cells and in extracellular body fluids (1). Because the direct measurement of RONS is difficult to perform, thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PCs) have been employed as markers of prooxidation (1). Glutathione (GSH) and oxidized glutathione disulfide (GSSG), the enzymes glutathione peroxidase (GPX) and catalase and the so-called total antioxidant capacity (TAC) have been employed as markers of antioxidation (2-4). Oxidative stress in humans has been associated with obesity and resulting comorbidities (1,5,6). Childhood obesity has been associated with oxidative stress even before comorbidities occur (6,7).Puberty is a maturation period in human development, when sexual characteristics and reproductive competence are developed (8). It is characterized by changes in the dynamically regulated hypothalamic-growth hormone (GH)-insulin-like growth factor (IGF)-1 and hypothalamic-pituitary-gonadal axes (9). ...

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