Ligation of the uterine arteries (LIG) in rats serves as a model of intrauterine growth restriction and subsequent developmental programming of impaired glucose tolerance, hyperinsulinemia, and adiposity in the offspring. Its impact on lipid metabolism has been less well investigated. We compared parameters of glucose and lipid metabolism and glucocorticoid levels in the offspring of dams that underwent either LIG or sham operation (SOP) with those of untreated controls. Blood parameters including insulin, leptin, and visfatin as well as body weight, food intake, and creatinine clearance were recorded up to an age of 30 wk. Glucose tolerance tests were performed, and both leptin and visfatin expression in liver, muscle, and epididymal and mesenteric fat was quantified by RT-PCR. After catch-up growth, weight gain of all groups was similar, despite lower food intake of the LIG rats. LIG offspring showed impaired glucose tolerance from the age of 15 wk as well as elevated glycosylated hemoglobin and corticosterone levels. However, the body fat content of both LIG and SOP animals increased relative to controls, and both showed elevated triglyceride, total cholesterol, and leptin levels as well as a reduced proportion of high-density lipoprotein cholesterol. Thus, use of the LIG model requires both SOP and untreated controls. Although only LIG is associated with impaired glucose tolerance, pathogenic programming of the lipid metabolism can also be induced by SOP. Visfatin does not appear to be involved in the disturbed glucose metabolism after intrauterine growth restriction and may represent only a marker of fat accumulation.

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Arterial blood pressure, renal function, and proteinuria after 14 days of GN were not influenced by former IUGR. Conclusion: Ligation of the uterine arteries in the rat leads to more pronounced sclerotic changes in the glomerulus in the offspring suffering from acute GN. This finding supports the hypothesis that former IUGR increases the susceptibility for a more severe course of secondary renal diseases.

Background. Resistin is a newly discovered peptide hormone that inhibits adipogenesis. Furthermore, it may be involved in regulative processes taking place in insulin resistance and inflammation. In human beings as well as in rodents, the exact physiological role of resistin is unknown. The objective of this study was to examine whether resistin serum concentrations in childhood are regulated by renal function. Methods. Fifteen patients with end stage renal disease treated by haemodialysis (HD) (6m, 9f; age (median (25-75% percentile)) 16.1 (14.2-16.9) years; body mass index (BMI) 17.8 (17.6-20.6) kg/m 2 ; glomerular filtration rate (GFR)<10 ml/min/1.73 m 2 ), 11 patients with chronic renal failure (CRF) (4m, 7f; age 11.3 (9.2-16.9) years; BMI 17.9 (15.4-22.1) kg/m 2 ; GFR 21.2 (19.8-39.4) ml/min/1.73 m 2 ) and 23 healthy children (13m, 10f; age 7.8 (4.7-14.5) years; BMI 16.5 (14.9-18.1) kg/m 2 ; GFR 168.5 (154.0-197.2) ml/min/ 1.73 m 2 ) were included. Resistin concentration in serum was measured by ELISA, leptin by RIA. Results. Resistin concentrations were significantly elevated in HD (6.6 (5.7-8.7) ng/ml) and CRF (4.8 (4.1-6.2) ng/ml) compared to healthy controls [2.7 (2.0-3.6) ng/ml; P<0.0001 by multiple regression analysis]. Furthermore, resistin concentrations showed a tendency to be higher in children below the age of 5.5 years (youngest tertile) and above 12.5 years of age (oldest tertile), compared to children aged between 5.5 and 12.5 years (P ¼ 0.053 and P ¼ 0.043, respectively). Gender (P ¼ 0.686) and BMI (P ¼ 0.663) did not have a significant influence on resistin concentrations. Resistin and leptin serum concentrations correlated in HD patients only (r ¼ 0.62, P ¼ 0.013 by Spearman correlation). Haemodialysis did not eliminate resistin. Conclusions.With decreasing renal function, resistin concentration in serum increases in our small paediatric cohort. Age possibly influences circulating resistin concentration. The hypothesis that elevated serum resistin in children with chronic renal failure or end stage renal disease may add to malnutrition and reduced BMI needs further investigation and is not supported by our data.

Individuals with intrauterine growth restriction (IUGR) are at risk for chronic lung disease. Using a rat model, we showed in our previous studies that altered lung structure is related to IL-6/STAT3 signaling. As neuropeptide Y (NPY), a coneurotransmitter of the sympathetic nervous system, regulates proliferation and immune response, we hypothesized that dysregulated NPY after IUGR is linked to IL-6, impaired myofibroblast function, and alveolar growth. IUGR was induced in rats by isocaloric low-protein diet; lungs were analyzed on embryonic day (E) 21, postnatal day (P) 3, P12, and P23. Finally, primary neonatal lung myofibroblasts (pnF) and murine embryonic fibroblasts (MEF) were used to assess proliferation, apoptosis, migration, and IL-6 expression. At E21, NPY and IL-6 expression was decreased, and AKT/PKC and STAT3/AMPKα signaling was reduced. Early reduction of NPY/IL-6 was associated with increased chord length in lungs after IUGR at P3, indicating reduced alveolar formation. At P23, however, IUGR rats exhibited a catch-up of body weight and alveolar growth coupled with more proliferating myofibroblasts. These structural findings after IUGR were linked to activated NPY/PKC, IL-6/AMPKα signaling. Complementary, IUGR-pnF showed increased survival, impaired migration, and reduced IL-6 compared with control-pnF (Co-pnF). In contrast, NPY induced proliferation, migration, and increased IL-6 synthesis in fibroblasts. Additionally, NPY mice showed reduced IL-6 signaling and less proliferation of lung fibroblasts. Our study presents a novel role of NPY during alveolarization: NPY regulates ) IL-6 and lung STAT3/AMPKα signaling, and) proliferation and migration of myofibroblasts. These new insights in pulmonary neuroimmune interaction offer potential strategies to enable lung growth.