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Dietary administration of D-chiro-inositol attenuates sex-specific metabolic imbalances in the 5xFAD mouse model of Alzheimer's disease
SIMON, Vincent
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
COTA, Daniela
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
< Reduce
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Language
EN
Article de revue
This item was published in
Biomedicine & pharmacotherapy. 2022-06, vol. 150, p. 112994
English Abstract
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 ...Read more >
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. © 2022 The AuthorsRead less <
English Keywords
Alzheimer’s disease
D-chiro-inositol
Fatty liver disease
Hypothalamus
Inflammation
Insulin signaling
Link to research data
European Project
Defining a Roadmap for Cooperative Health research between the EU and Latin America-Caribbean countries: a Policy Oriented Approach
ANR Project
Rôle du récepteur aux cannabinoïdes de type 1 mitochondriale dans les circuits hypothalamiques et son interaction avec la voie mTORC1 dans l'obésité.
Bordeaux Region Aquitaine Initiative for Neuroscience
Innovations instrumentales et procédurales en psychopathologie expérimentale chez le rongeur - ANR-10-EQPX-0008
La signalisation des acides biliaires dans le cerveau et son rôle dans le contrôle métabolique - ANR-17-CE14-0007
Rôle du circuit POMC-striatum ventral dans le développement de l'obésité - ANR-21-CE14-0018
Développment d'une infrastructure française distribuée coordonnée
Bordeaux Region Aquitaine Initiative for Neuroscience
Innovations instrumentales et procédurales en psychopathologie expérimentale chez le rongeur - ANR-10-EQPX-0008
La signalisation des acides biliaires dans le cerveau et son rôle dans le contrôle métabolique - ANR-17-CE14-0007
Rôle du circuit POMC-striatum ventral dans le développement de l'obésité - ANR-21-CE14-0018
Développment d'une infrastructure française distribuée coordonnée
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