Oral leptin supplementation throughout lactation ameliorates neuroanatomic consequences in the offspring caused by maternal moderate caloric restriction during gestation.

J. KONIECZNA; J. SÁNCHEZ; A. P. GARCÍA; M. PALOU; A. PALOU; C. PICÓ

Granada

Congreso; 20th International Congress of Nutrition; 2013

Background and objectives: In the present study, we used an experimental rat model of moderate (20%) maternal caloric restriction during pregnancy, which is known to be associated with alterations in hypothalamic circuitry that program a higher propensity to develop obesity in the offspring, to investigate whether oral supplementation with physiological doses of leptin throughout lactation may ameliorate the developmental malprogramming effects exerted in offspring hypothalamus structure and function. Methods: Male and female rats belonging to 3 groups were studied: the offspring of ad libitum fed dams (controls), the offspring of 20% calorie restricted dams during the first part of pregnancy (CR), and CR rats supplemented with physiological doses of leptin throughout lactation (CR-Leptin). Animals were sacrificed on postnatal day 25. Morphometric and immunohistochemical studies on arcuate (ARC) and paraventicular (PVN) nucleus were performed and hypothalamic expression levels of selected genes were determined. Results: In CR males, leptin treatment restored, at least in part, the number of immunoreactive NPY (NPY+) cells in ARC, the total number of cells in PVN, hypothalamic NPY, CART and SOCS-3 mRNA levels, and plasma leptin levels, which were decreased in CR animals. CR-Leptin males showed higher hypothalamic ObRb mRNA levels, compared to control and CR animals. In CR females, leptin treatment reverted the increased number of cells in ARC and of cell density in ARC and PVN, and reduced hypothalamic SOCS-3 mRNA expression to levels similar to controls. Leptin treatment also reverted the increased relative area of NPY+ fibers in the PVN occurring in CR animals. Conclusion: Results suggest that leptin supplementation throughout lactation is able to ameliorate adverse developmental effects on hypothalamic structure and function, making the metabolic malprogramming induced by maternal caloric restriction during gestation reversible to some extent.