Carrillo Urbano, BeatrizCollado Guirao, PalomaDíaz, FranciscaChowen, Julie A.Pérez Izquierdo, María ÁngelesPinos Sánchez, María Elena2024-12-302024-12-302017-07-11Carrillo, B., Collado, P., Díaz, F., Chowen, J. A., Pérez-Izquierdo, M. Á., & Pinos, H. (2017). Physiological and brain alterations produced by high-fat diet in male and female rats can be modulated by increased levels of estradiol during critical periods of development. Nutritional Neuroscience, 22(1), 29–39. https://doi.org/10.1080/1028415X.2017.13495741028-415Xhttps://doi.org/10.1080/1028415X.2017.1349574https://hdl.handle.net/20.500.14468/25067Este es el manuscrito aceptado del artículo. La versión registrada fue publicada por primera vez en Nutritional Neuroscience, 22(1), 29–39, está disponible en línea en el sitio web del editor: https://doi.org/10.1080/1028415X.2017.1349574. This is the accepted manuscript of the article. The copyrighted version was first published in Nutritional Neuroscience, 22(1), 29–39, and is available online at the publisher's website: https://doi.org/10.1080/1028415X.2017.1349574.Background: Overnutrition due to a high-fat diet (HFD) can increase the vulnerability of the metabolic system to maladjustments. Estradiol has an inhibitory role on food intake and this hormone has demonstrated to be a crucial organizer during brain development. Objective: Our aim was to determine whether increased levels of estradiol in the early postnatal period modulate the alterations in metabolism and brain metabolic circuits produced by overnutrition. Methods: Twenty-four male and 24 female Wistar rats were submitted to a HFD (34.9% fat) or a control diet (5% fat) from gestational day 6. From postnatal (P) 6 to P13, both control and HFD groups were administered a s.c. injection of vehicle or estradiol benzoate (0.4 mg/kg), resulting in eight experimental groups (n = 6 in each group). Body weight, food intake and subcutaneous, visceral, and brown fat pads were measured. Agouti-related peptide, neuropeptide Y, orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay and plasma estradiol levels were measured by ELISA. Results: Males fed a HFD showed an increase in body weight and the amount of visceral and subcutaneous fat, which was coincident with an increase in the number of kilocalories ingested. Neonatal estradiol treatment restored the body weight and subcutaneous fat of HFD males to control levels. Hypothalamic POMC mRNA levels in HFD females were increased with respect to control females. This increase was reverted with estradiol treatment during development. Discussion: HFD and estradiol treatment have different effects on males and females. Overnutrition affects physiological parameters, such as body weight, visceral, and subcutaneous fat content, in males, while females present alterations in hypothalamic POMC mRNA levels. Hence, the increase in estradiol levels during a period that is critical for the programing of the feeding system can modulate some of the alterations produced by the continuous intake of high-fat content food.eninfo:eu-repo/semantics/openAccess61 PsicologíaartículoHigh-fat dietshort-term estradiol treatmentprograming feeding systemorexigenic anorexigenic peptidespcr-rat-sex differences