Maternal High Fat Diet Alters Hypothalamic NPY and Gastric Hormone Ghrelin Levels in Offspring: Protective Role of N-Acetylcysteine in Early Obesity Programming

The aim of this study was to determine whether N-acetylcysteine (NAC) administration attenuates the adverse effects on the hypothalamic gastric axis in the offspring of rat dams given a high-fat diet (HFD) during pregnancy and lactation. A maternal obesity model was established using a 60% k/cal HFD. Both the NAC and obesity + NAC (Ob + NAC) groups received NAC (150 mg/kg) by oral gavage from the beginning of pregnancy until postnatal day 25. All female pups were sacrificed at eight weeks of age. Arcuate (ARC) nucleus volumes were analyzed stereologically, and neuropeptide (NPY) concentrations were determined biochemically in hypothalamus tissues. Immunohistochemically, ghrelin expression was analyzed from stomach tissue sections, and ghrelin levels were determined in blood samples. The total volume of the ARC region and NPY concentrations increased in the obesity group. A tendency towards a decrease in gastric ghrelin expression was also observed in the obesity group, and biochemical examination of blood samples revealed a decrease in ghrelin levels. Our results show that NAC supplementation protects the ARC volume and NPY concentrations in the hypothalamus and ghrelin levels in the blood against maternal obesity. In conclusion, ghrelin levels may affect hypothalamic neuronal programming during early development, leading to an increase in ARC volume. This may lead to hyperphagia and weight gain and may be responsible for the development of obesity in adulthood. In addition, NAC supplementation in mothers receiving an HFD may reduce the risk of obesity in the long term by eliminating the deleterious metabolic effects caused in offspring.