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 Lopez-Gambero, Antonio J
A1 Pacheco-Sanchez, Beatriz
A1 Rosell-Valle, Cristina
A1 Medina-Vera, Dina
A1 Navarro, Juan Antonio
A1 Fernandez-Arjona, Maria Del Mar
A1 de-Ceglia, Marialuisa
A1 Sanjuan, Carlos
A1 Simon, Vincent
A1 Cota, Daniela
A1 Rivera, Patricia
A1 Rodriguez-de-Fonseca, Fernando
A1 Suarez, Juan
K1 Alzheimer’s disease
K1 D-chiro-inositol
K1 Fatty liver disease
K1 Hypothalamus
K1 Inflammation
K1 Insulin signaling
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 2022-04-26
LK http://hdl.handle.net/10668/22043
UL http://hdl.handle.net/10668/22043
LA en
NO López-Gambero AJ, Pacheco-Sánchez B, Rosell-Valle C, Medina-Vera D, Navarro JA, Fernández-Arjona MDM, et al. Dietary administration of D-chiro-inositol attenuates sex-specific metabolic imbalances in the 5xFAD mouse model of Alzheimer's disease. Biomed Pharmacother. 2022 Jun;150:112994
DS RISalud
RD Apr 8, 2025