Aim: We aimed to investigate whether maternal
malnutrition during gestation/lactation induces long-lasting changes on
inflammation, lipid metabolism and
endocannabinoid signaling in the adult offspring hypothalamus and the role of hypothalamic astrocytes in these changes.Methods: We analyzed the effects of a free-choice hypercaloric palatable diet (P) during (pre)gestation, lactation and/or post-weaning on
inflammation, lipid metabolism and endogenous
cannabinoid signaling in the adult offspring hypothalamus. We also evaluated the response of primary hypothalamic astrocytes to
palmitic acid and
anandamide.Results: Postnatal exposure to a P diet induced factors involved in hypothalamic
inflammation (Tnfa and
Il6) and
gliosis (Gfap,
vimentin and Iba1) in adult offspring, being more significant in females. In contrast, maternal P diet reduced factors involved in
astrogliosis (
vimentin),
fatty acid oxidation (Cpt1a) and
monounsaturated fatty acid synthesis (Scd1). These changes were accompanied by an increase in the expression of the genes for the
cannabinoid receptor (Cnr1) and Nape-
pld, an
enzyme involved in
endocannabinoid synthesis, in females and a decrease in the
endocannabinoid degradation
enzyme Faah in males. These changes suggest that the maternal P diet results in sex-specific alterations in hypothalamic
endocannabinoid signaling and lipid metabolism. This hypothesis was tested in hypothalamic astrocyte cultures, where
palmitic acid (PA) and the
polyunsaturated fatty acid N-arachidonoylethanolamine (
anandamide or AEA) were found to induce similar changes in the
endocannabinoid system (ECS) and lipid metabolism.Conclusion: These results stress the importance of both maternal diet and sex in long term metabolic programming and suggest a possible role of hypothalamic astrocytes in this process.