Search

Low birth weight (LBW) is associated with type 2 diabetes and depression, which may be related to prenatal stress and insulin resistance as a result of chronic hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We examined whether treatment with a selective serotonin reuptake inhibitor [escitalopram (ESC)] could downregulate HPA axis activity and restore insulin sensitivity in LBW rats. After 4-5 wk of treatment, ESC-exposed LBW (SSRI-LBW) and saline-treated control and LBW rats (Cx and LBW) underwent an oral glucose tolerance test or a hyperinsulinemic euglycemic clamp to assess whole body insulin sensitivity. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression and red skeletal muscle PKB Ser[sup.473] phosphorylation were used to assess tissue-specific insulin sensitivity, mRNA expression of the hypothalamic mineralocorticoid receptor was five-fold upregulated in LBW (P < 0.05 vs. Cx), accompanied by increased corticosterone release during restraint stress and total 24-h urinary excretion (P < 0.05 vs. Cx), whole body insulin resistance (P < 0.001 vs. Cx), and impaired insulin suppression of hepatic PEPCK mRNA expression (P < 0.05 vs. Cx). Additionally, there was a tendency for reduced red muscle PKB Ser[sup.473] phosphorylation. The ESC treatment normalized corticosterone secretion (P < 0.05 vs. LBW), whole body insulin sensitivity (P < 0.01) as well as postprandial suppression of hepatic mRNA PEPCK expression (P < 0.05), and red muscle PKB Ser[sup.473] phosphorylation (P < 0.01 vs. LBW). We conclude that these data suggest that the insulin resistance and chronic HPA axis hyperactivity in LBW rats can be reversed by treatment with an ESC, which downregulates HPA axis activity, lowers glucocorticoid exposure, and restores insulin sensitivity in LBW rats. selective serotonin reuptake inhibitors doi:10.1152/ajpendo.00606.2009.

Low birth weight is associated with an increased risk of hypertension and renal dysfunction at adulthood. Such an association has been shown to involve a reduction of nephron endowment and to be enhanced by accelerated postnatal growth in humans. However, while low-birth-weight infants often undergo catch-up growth, little is known about the long-term vascular and renal effects of accelerated postnatal growth. We surimposed early postnatal overfeeding (OF; reduction of litter size during the suckling period) to appropriate-birth-weight (NBW+OF) and intrauterine growth restriction (IUGR; IUGR+OF) pups, obtained after a maternal gestational low-protein diet. Blood pressure (systolic blood pressure; SBP) and renal function (glomerular filtration rate; GFR) were measured in young and aging offspring. Glomerulosclerosis and nephron number were determined in aging offspring (22 too). Nephron number was reduced in both IUGR and IUGR+OF male offspring (by 24 and 26%). GFR was reduced by 40% in 12-too-old IUGR+OF male offspring, and both NBW+OF and IUGR+OF aging male offspring had sustained hypertension (+25 mmHg) and glomernlosclerosis, while SBP and renal function were unaffected in IUGR aging offspring. Female offspring were unaffected. In conclusion, in this experimental model, early postnatal OF in the neonatal period has major long-lasting effects. Such effects are gender dependent. Reduced nephron number alone, associated with IUGR, may not be sufficient to induce long-lasting physiological alterations, and early postnatal OF acts as a 'second hit.' Early postnatal OF is a suitable model with which to study the long-term effects of postnatal growth in the pathogenesis of vascular disorders and renal disease. nephrogenesis; nephron number; catch-up growth; hypertension; glomernlosclerosis; developmental origins of adult diseases; low birth weight doi:10.1152/ajprenal.90704.2008.

Epidemiological studies demonstrated a relationship between low birth weight mainly caused by intrauterine growth restriction (IUGR) and adult metabolic disorders. The concept of metabolic programming centers on the idea that nutritional and hormonal status during the key period of development determines the long-term control of energy balance by programming future feeding behavior and energy expenditure. The present study examined the consequence of early or late 'catch-up growth' after IUGR on feeding behavior and metabolic cues of male offspring of rat dams exposed to protein restriction during gestation and/or lactation. Our results suggest that early catch-up growth may be favorable for fasting metabolic parameters at weaning, as no differences were observed on plasma leptin, triglyceride, glucose, and insulin levels compared with controls. In contrast, if pups remained malnourished until weaning, low insulin concentration was detected and was accompanied by hyperphagia associated with a large increase in hypothalamic NPY and AgRP mRNA expression. At adult age, on a regular chow diet, only the meal structure was modified by fetal programming. The two IUGR groups demonstrated a reduced meal duration that enhanced the speed of food ingestion and consequently increased the rest period associated to the satiety state without changes in the hypothalamic expression of appetite neuropeptides. Our findings demonstrate that in IUGR, regardless of postnatal growth magnitude, metabolic programming occurred in utero and was responsible for both feeding behavior alteration and postprandial higher insulin level in adults. Additionally, catch-up growth immediately after early malnutrition could be a key point for the programming of postprandial hyperleptinemia. perinatal nutrition; appetite neuropeptides; hypothalamus; feeding behavior

Forty-one children aged 10.5 [+ or -] 0.2 years (range, 8.0-15.0 yr), born with low birth weight of 1,218.2 [+ or -] 36.6 g (range, 765-1,580 g) were selected from hospital archives on the basis of whether they had received neonatal diuretic treatment or as healthy matched controls. The children were tested for salt appetite and sweet preference, including rating of preferred concentration of salt in tomato soup (and sugar in tea), ratings of oral spray (NaCl and sucrose solutions), intake of salt or sweet snack items, and a food-seasoning, liking, and dietary questionnaire. Results showed that sodium appetite was not related to neonatal diuretic treatment, birth weight, or gestational age. However, there was a robust inverse correlation (r = -0.445, P < 0.005) between reported dietary sodium intake and the neonatal lowest serum sodium level (NLS) recorded for each child as an index of sodium loss. The relationship of NLS and dietary sodium intake was found in both boys and girls and in both Arab and Jewish children, despite marked ethnic differences in dietary sources of sodium. Hence, low NLS predicts increased intake of dietary sodium in low birth weight children some 8-15 yr later. Taken together with other recent evidence, it is now clear that perinatal sodium loss, from a variety of causes, is a consistent and significant contributor to long-term sodium intake. dietary sodium; humans; hyponatremia; neonates; perinatal programming; sodium appetite

Epidemiological studies suggest that infants of low birth weight show poor neonatal growth and increased susceptibility to adult diseases such as diabetes and lung disease. Uncoupling protein 2 and 3 (UCP2 and UCP3) have been implicated in the development of such diseases; pigs provide an ideal model to examine the influence of birth weight due to the natural variance in piglet weight within a litter. This study examined whether birth weight influences the expression of UCP2 and UCP3 in adipose tissue, skeletal muscle, and lung. Piglets from 11 litters were ranked according to birth weight and three from each litter assigned to small (SFD), normal (NFD), or large for dates (LFD) groups. Blood samples and morphometric measurements were taken over the first 14 days of life, and tissue samples were taken on day 7 or 14. Plasma hormone and metabolite concentrations and the expression of UCP2 and UCP3 mRNA in adipose tissue, skeletal muscle, and lung were measured. UCP2 and UCP3 expression in adipose tissue was lower in the SFD compared with the LFD group on day 7. UCP3 expression in skeletal muscle was higher than that of adipose tissue. Lung UCP2 and skeletal muscle UCP3 mRNA expression were unaffected by size at birth. Regression analysis indicated that UCP3 expression was differentially associated with IGF-1, leptin, and insulin. In conclusion, low birth weight is associated with tissue-specific effects on UCP expression. It remains to be established whether these subsequently contribute to pathological conditions such as diabetes. mitochondria; postnatal growth; metabolism