ABSTRACT
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.
Data availability statement
The data that support the findings of this study are available on reasonable request from the corresponding author.
Disclosure statement
No potential conflict of interest was reported by the author(s).
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Notes on contributors
Patricia Rivera
Patricia Rivera is a Postdoctoral Researcher in the Neuropsychopharmacology group of the IBIMA Institute. The group has a extensive experience in the development of new drugs for the treatment of disorders related to motivational behavior, especially in obesity and drugs of abuse areas.
Santiago Guerra-Cantera
Santiago Guerra-Cantera is a Ph.D. student in the Department of Endocrinology at Hospital Infantil Universitario Niño Jesús.
Antonio Vargas
Antonio Vargas is laboratory technician in the Neuropsychopharmacology group of the IBIMA Institute.
Francisca Díaz
Francisca Díaz is a postdoctoral Researcher in the Department of Endocrinology at Hospital Infantil Universitario Niño Jesús.
Rocío García-Úbeda
Rocío García-Úbeda is a postdoctoral Researcher in the Department of Endocrinology at Hospital Infantil Universitario Niño Jesús.
Rubén Tovar
Rubén Tovar is a Ph.D. student in the Neuropsychopharmacology group of the IBIMA Institute.
María Teresa Ramírez-López
María Teresa Ramírez-López is a postdoctoral Researcher in the Universitary Hospital of Getafe.
Jesús Argente
Jesús Argente (M.D., Ph.D) is Full Professor of Pediatrics at Universidad Autónoma of Madrid and Chief of Pediatrics and of Pediatric Endocrinology at Hospital Infantil Universitario Niño Jesús. His research includes the endocrinology of pathological growth, puberty and metabolism.
Fernando Rodríguez de Fonseca
Fernando Rodríguez de Fonseca led Neuropsychopharmacology group of the IBIMA Institute.
Juan Suárez
Juan Suárez is a Postdoctoral Researcher in the Neuropsychopharmacology group of the IBIMA Institute.
Julie A. Chowen
Julie A. Chowen (Ph.D.) is Senior Researcher in the Department of Endocrinology at Hospital Infantil Universitario Niño Jesús. Her research is focused on the neuroendocrine control of energy balance with a special interest in the role of astrocytes in this process.