Maternal obesity (MO) programs morphological changes in aged rat offspring small intestine in a sex dependent manner: Effects of maternal resveratrol supplementation.

Maternal obesity (MO) leads to offspring metabolic problems. The mechanisms involved are multifactorial. The small intestine plays an important role in the absorption of nutrients and is modified as we age. Few studies have explored MO programming effects on offspring (F1) small intestine morphology. The aim of this study was to investigate MO effects on old adult F1 intestinal morphology, and whether any F1 intestinal changes due to MO were modified by maternal resveratrol supplementation. From weaning throughout pregnancy and lactation, female Wistar rats (F0) ate standard chow (controls, C: 5%-fat) or high-fat diet (MO: 25%-fat). One month before mating at postnatal day (PND) 120 through lactation half of each group received 20 mg/kg/day of resveratrol orally (Cres or MOres). After weaning F1 were fed with chow diet until the end of the study at PND 650. Body weight, percent of fat, glucose, cholesterol and triglyceride serum concentrations were determined. F1 small intestinal samples were collected for histological analysis. Male F1 body weight was higher in MO and MOres compared with C and Cres. Female F1 body weight and percent of fat was higher in MO than C and MOres. Triglyceride concentrations were higher in MO and MOres male F1 compared with C and Cres. There were no differences among groups in female triglyceride concentrations. Male F1 duodenal villus height was smaller in MO compared with MOres. Female F1 duodenal and jejunal crypt depth was smaller in MO compared with C and was greater compared with MOres. Female F1 villus height in jejunum was greater in MO compared with MOres. In conclusion, exposure to the developmental challenge of MO changed the aged F1 intestinal morphological and metabolic profiles. Maternal resveratrol supplementation ameliorated these effects in an F1 sex dependent manner.

Maternal obesity induced by diet in rats permanently influences central processes regulating food intake in offspring.

Hypothalamic systems which regulate appetite may be permanently modified during early development. We have previously reported hyperphagia and increased adiposity in the adult offspring of rodents fed an obesogenic diet prior to and throughout pregnancy and lactation. We now report that offspring of obese (OffOb) rats display an amplified and prolonged neonatal leptin surge, which is accompanied by elevated leptin mRNA expression in their abdominal white adipose tissue. At postnatal Day 30, before the onset of hyperphagia in these animals, serum leptin is normal, but leptin-induced appetite suppression and phosphorylation of STAT3 in the arcuate nucleus (ARC) are attenuated; the level of AgRP-immunoreactivity in the hypothalamic paraventricular nucleus (PVH), which derives from neurones in the ARC and is developmentally dependent on leptin, is also diminished. We hypothesise that prolonged release of abnormally high levels of leptin by neonatal OffOb rats leads to leptin resistance and permanently affects hypothalamic functions involving the ARC and PVH. Such effects may underlie the developmental programming of hyperphagia and obesity in these rats.

Maternal dietary supplementation with saturated, but not monounsaturated or polyunsaturated fatty acids, leads to tissue-specific inhibition of offspring Na+,K+-ATPase.

In rats, a maternal diet rich in lard is associated with reduced Na(+),K(+)-ATPase activity in adult offspring kidney. We have addressed the role of different fatty acids by evaluating Na(+),K(+)-ATPase activity in offspring of dams fed diets rich in saturated (SFA), monounsaturated (MUFA) or polyunsaturated (PUFA) fatty acids. Female Sprague-Dawley rats were fed, during pregnancy and suckling, a control diet (4% w/w corn oil) or a fatty acid supplemented diet (24% w/w). Offspring were reared on chow (4% PUFA) and studied at 6 months. mRNA expression (real-time PCR) of Na(+),K(+)-ATPase alpha subunit and protein expression of Na(+),K(+)-ATPase subunits (Western blot) were assessed in kidney and brain. Na(+),K(+)-ATPase activity was reduced in kidney (P < 0.05 versus all groups) and brain (P < 0.05 versus control and MUFA offspring) of the SFA group. Neither Na(+),K(+)-ATPase alpha1 subunit mRNA expression, nor protein expression of total alpha, alpha1, alpha2, alpha3 or beta1 subunits were significantly altered in kidney in any dietary group. In brains of SFA offspring alpha1 mRNA expression (P < 0.05) was reduced compared with MUFA and PUFA offspring, but not controls. Also in brain, SFA offspring demonstrated reduced (P < 0.05) alpha1 subunit protein and increased phosphorylation (P < 0.05) of the Na(+),K(+)-ATPase modulating protein phospholemman at serine residue 63 (S63 PLM). Na(+),K(+)-ATPase activity was similar to controls in heart and liver. In utero and neonatal exposure to a maternal diet rich in saturated fatty acids is associated with altered activity and expression of Na(+),K(+)-ATPase in adulthood, but mechanisms appear tissue specific.