Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/264787
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | BACE2 suppression in mice aggravates the adverse metabolic consequences of an obesogenic diet |
Autor: | Díaz-Catalán, Daniela; Alcarraz-Vizán, Gema; Castaño, Carlos; Pablo, Sara de; Rodríguez-Comas, Júlia; Fernández-Pérez, Antonio CSIC ORCID; Vallejo, Mario CSIC ORCID; Ramírez, Sara; Claret, Marc; Párrizas, Marcelina; Novials, Anna; Servitja, Joan-Marc | Palabras clave: | BACE2 High-fat diet β-cell proliferation Insulin secretion Insulin resistance Leptin |
Fecha de publicación: | nov-2021 | Editor: | Elsevier | Citación: | Molecular Metabolism 53: 101251 (2021) | Resumen: | [Objective]: Pancreatic β-cell dysfunction is a central feature in the pathogenesis of type 2 diabetes (T2D). Accumulating evidence indicates that β-site APP-cleaving enzyme 2 (BACE2) inhibition exerts a beneficial effect on β-cells in different models of T2D. Thus, targeting BACE2 may represent a potential therapeutic strategy for the treatment of this disease. Here, we aimed to investigate the effects of BACE2 suppression on glucose homeostasis in a model of diet-induced obesity. [Methods]: BACE2 knock-out (BKO) and wild-type (WT) mice were fed with a high-fat diet (HFD) for 2 or 16 weeks. Body weight, food intake, respiratory exchange ratio, locomotor activity, and energy expenditure were determined. Glucose homeostasis was evaluated by glucose and insulin tolerance tests. β-cell proliferation was assessed by Ki67-positive nuclei, and β-cell function was determined by measuring glucose-stimulated insulin secretion. Leptin sensitivity was evaluated by quantifying food intake and body weight after an intraperitoneal leptin injection. Neuropeptide gene expression and insulin signaling in the mediobasal hypothalamus were determined by qPCR and Akt phosphorylation, respectively. [Results]: After 16 weeks of HFD feeding, BKO mice exhibited an exacerbated body weight gain and hyperphagia, in comparison to WT littermates. Glucose tolerance was similar in both groups, whereas HFD-induced hyperinsulinemia, insulin resistance, and β-cell expansion were more pronounced in BKO mice. In turn, leptin-induced food intake inhibition and hypothalamic insulin signaling were impaired in BKO mice, regardless of the diet, in accordance with deregulation of the expression of hypothalamic neuropeptide genes. Importantly, BKO mice already showed increased β-cell proliferation and glucose-stimulated insulin secretion with respect to WT littermates after two weeks of HFD feeding, before the onset of obesity. [Conclusions]: Collectively, these results reveal that BACE2 suppression in an obesogenic setting leads to exacerbated body weight gain, hyperinsulinemia, and insulin resistance. Thus, we conclude that inhibition of BACE2 may aggravate the adverse metabolic effects associated with obesity. |
Descripción: | © 2021 The Author(s). | Versión del editor: | http://dx.doi.org/10.1016/j.molmet.2021.101251 | URI: | http://hdl.handle.net/10261/264787 | DOI: | 10.1016/j.molmet.2021.101251 | E-ISSN: | 2212-8778 |
Aparece en las colecciones: | (IIBM) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
BACE2_suppression_in_mice_aggravates_Díaz_PV_Art2021.pdf | 2,12 MB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
3
checked on 27-abr-2024
SCOPUSTM
Citations
4
checked on 28-abr-2024
WEB OF SCIENCETM
Citations
3
checked on 23-feb-2024
Page view(s)
47
checked on 06-may-2024
Download(s)
47
checked on 06-may-2024