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Maternal nutritional environmental in early life has been often associated with long term effects on the immune response in adulthood. The effects of maternal protein deprivation during early lactation on neutrophil-mediated innate immunity were investigated in adult rats, offspring of dams fed with a protein-free diet during the first days of lactation (PD), and compared to controls (22% protein diet). Inflamed PD animals showed an inhibited neutrophil migration and an impaired recruitment of leukocytes from bone marrow pool to circulation. In resting conditions, blood neutrophils from PD present reduced phagocytic activity, increased production of O(2) (-) and NO, basal iNOS expression and constitutive NF-kappaB activation. Moreover, PD rats also show high circulating levels of TNF-alpha and increased expression of TNF-alpha mRNA in the spleen and liver. The data indicate that maternal nutritional stress can interfere on the innate immune response in adulthood, imprinting permanent alterations on cytokine production and neutrophil activation.

Overnutrition during critical developmental periods is believed to be a risk factor for the emergence of metabolic disorders in adulthood. The present study investigated the effects of pups overfeeding during lactation on offspring's insulin secretion. To study the consequences of overnutrition early in life in rats, litter size reduction has been shown to be an appropriate experimental model. To induce early postnatal overnutrition, litter size was reduced to three pups per litter at the third day following birth [overfed group (OG)]. In the control group (CG), the litter size was adjusted to 10 pups per litter. Metabolic parameters and glucose-stimulated insulin secretion were assessed. OG pups ingested more milk at 10 and 21 days and had an augmented food intake at 1 year compared to the CG. Consistently, body weight, body fat, and fasting plasma levels of insulin were higher in 1-year-old OG rats. In addition, OG rats exhibited enhanced insulin secretion, accompanied by elevated content of GLUT-2 in pancreatic islets compared to CG. These findings indicate that early postnatal overnutrition during a critical developmental period in life may program permanent alterations in glucose-stimulated insulin secretion.

Epidemiological and experimental studies have demonstrated that early postnatal nutrition has been associated with long-term effects on glucose homeostasis in adulthood. Recently, our group demonstrated that undernutrition during early lactation affects the expression and activation of key proteins of the insulin signaling cascade in rat skeletal muscle during postnatal development. To elucidate the molecular mechanisms by which undernutrition during early life leads to changes in insulin sensitivity in peripheral tissues, we investigated the insulin signaling in adipose tissue. Adipocytes were isolated from epididymal fat pads of adult male rats that were the offspring of dams fed either a normal or a protein-free diet during the first 10 days of lactation. The cells were incubated with 100 nM insulin before the assays for immunoblotting analysis, 2-deoxyglucose uptake, immunocytochemistry for GLUT4, and/or actin filaments. Following insulin stimulation, adipocytes isolated from undernourished rats presented reduced tyrosine phosphorylation of IR and IRS-1 and increased basal phosphorylation of IRS-2, Akt, and mTOR compared with controls. Basal glucose uptake was increased in adipocytes from the undernourished group, and the treatment with LY294002 induced only a partial inhibition both in basal and in insulin-stimulated glucose uptake, suggesting an involvement of phosphoinositide 3-kinase activity. These alterations were accompanied by higher GLUT4 content in the plasma membrane and alterations in the actin cytoskeleton dynamics. These data suggest that early postnatal undernutrition impairs insulin sensitivity in adulthood by promoting changes in critical steps of insulin signaling in adipose tissue, which may contribute to permanent changes in glucose homeostasis.

The study investigated the effects of early life overfeeding on metabolic alterations, heart morphology and left ventricular insulin signaling pathway, mainly the glucose transporters GLUT1, GLUT4 and pAKT/AKT ratio. Wistar rats were overfed using the litter size reduction method. The pups were studies at age of 10 and 21 days. We measured heart GLUT1, GLUT4, AKT and pAKT. Animal weight and length, total body lipid, glycogen content, and the plasma levels of insulin, glucose, total cholesterol and triglycerides were measured. Cardiac hypertrophy was evaluated by heart weight/tibia length ratio. Our results showed that overfed animals were overweight, displayed high total body lipids, insulin, glucose, cholesterol and triglycerides plasma levels, and left ventricular hypertrophy with increasing of pAKT/AKT ratio. Moreover, the heart of overfed animals displayed a precocious translocation of GLUT4 and decreased content of GLUT1. In conclusion, we suggest that overfeeding during lactation might induce metabolic and cardiac alterations early in life, leading to the development of cardiac hypertrophy due anticipated insulin dependence created by earlier GLUT4 heart appearance. [ABSTRACT FROM AUTHOR]