RT Journal Article
T1 Dietary administration of D-chiro-inositol attenuates sex-specific metabolic imbalances in the 5xFAD mouse model of Alzheimer’s disease
A1 López-Gambero, Antonio J.
A1 Pacheco-Sánchez, Beatriz
A1 Rosell-del-Valle, Cristina
A1 Medina-Vera, Dina
A1 Navarro, Juan Antonio
A1 Fernández-Arjona, María del Mar
A1 De Ceglia, Marialuisa
A1 Sanjuán-Solís, Jesús Carlos
A1 Simon, Vincent
A1 Cota, Daniela
A1 Rivera-González, Patricia
A1 Rodriguez-de-Fonseca, Fernando
A1 Suárez-Pérez, Juan
K1 Alzheimer, Enfermedad de
AB Increasing evidence shows that hypothalamic dysfunction, insulin resistance, and weight loss precede and progress along with the cognitive decline in sporadic Alzheimer’s Disease (AD) with sex differences. This study aimed to determine the effect of oral dietary administration of D-Chiro-inositol (DCI), an inositol used against insulin resistance associated with polycystic ovary, on the occurrence of metabolic disorders in the transgenic 5xFAD mouse model of AD (FAD: Family Alzheimer's Disease). DCI was administered from 6 to 10 months of age to male and female 5xFAD mice and control (non-Tg) littermates. Energy balance and multiple metabolic and inflammatory parameters in the hypothalamus, liver and plasma were evaluated to assess the central and peripheral effects of DCI. Results indicated that weight loss and reduced food intake in 5xFAD mice were associated with decreased neuropeptides controlling food intake and the appearance of a pro-inflammatory state in the hypothalamus. Oral administration of DCI partially restored energy balance and hypothalamic parameters, highlighting an increased expression of Npy and Agrp and female-specific downregulation of Gfap and Igf1. DCI also partially normalized impaired insulin signaling and circulating insulin, GLP-1, and GIP deficiencies in 5xFAD mice. Principal component analysis of metabolic parameters indicated the presence of a female-specific fatty liver in 5xFAD mice: DCI administration reversed hepatic fat accumulation, β-oxidation, inflammation and increased GOT and GPT levels. Our study depicts that metabolic impairment along with the cognitive decline in a mouse model of AD, which is exacerbated in females, can be ameliorated by oral supplementation with insulin-sensitizing DCI.
PB Elsevier
YR 2022
FD 2022-06
LK https://hdl.handle.net/10630/24481
UL https://hdl.handle.net/10630/24481
LA eng
NO Antonio J. López-Gambero, Beatriz Pacheco-Sánchez, Cristina Rosell-Valle, Dina Medina-Vera, Juan Antonio Navarro, María del Mar Fernández-Arjona, Marialuisa de Ceglia, Carlos Sanjuan, Vincent Simon, Daniela Cota, Patricia Rivera, Fernando Rodríguez de Fonseca, Juan Suárez, Dietary administration of D-chiro-inositol attenuates sex-specific metabolic imbalances in the 5xFAD mouse model of Alzheimer’s disease, Biomedicine & Pharmacotherapy, Volume 150, 2022, 112994, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2022.112994
NO This research was funded by the European Regional Development Funds-European Union (ERDF-EU) and Fatzheimer project EULAC-HEALTH H2020, grant number EU-LACH16/T010131; Ministerio de Economía, Industria y Competitividad, Gobierno de España, grant number RTC-2016-4983-1; EU-ERDF and Instituto de Salud Carlos III (ISCIII), grant numbers PI19/01577 and PI19/00343; Ministerio de Sanidad, Delegación de Gobierno para el Plan Nacional sobre Drogas, grant numbers 2019/040 and 2020/048; Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía, grant number P18-TP-5194, INSERM (Institut National de la Santé et de la Recherche Médicale), Nouvelle Aquitaine Region and ANR (grant numbers ANR-18-CE14-0029 MitObesity, Labex BRAIN ANR-10-LABX-43, ANR-10-EQX-008-1 OPTOPATH, ANR-17-CE14-0007 BABrain, ANR-21-CE14-0018-01_StriaPOM to D.C.). A.J.L.-G. (IFI18/00042) holds an “iPFIS” predoctoral contract from the National System of Health, EU-ERDF-ISCIII. B.P.S (IFI21/00024) holds an “iPFIS” predoctoral contract from the National System of Health, EU-ERDF-ISCIII. P.R. (CP19/00068) holds a ‘’Miguel Servet I” research contract from the National System of Health, EU-ERDF-ISCIII. D.M-V. (FI20/00227) holds a “PFIS” pre-doctoral contract from the National System of Health, EU-ERDF-ISCIII. The microscopy for IBA1 and GFAP immunofluorescence was done in the Bordeaux Imaging Center, a service unit of the CNRS-INSERM and Bordeaux University, member of the national infrastructure France BioImaging supported by the LabEX BRAIN and ANR-10-INBS-04.  Partial funding for open access charge: Universidad de Málaga.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 15 abr 2026