Dietary administration of D-chiro-inositol attenuates sex-specific metabolic imbalances in the 5xFAD mouse model of Alzheimer’s disease
Biomedicine & Pharmacotherapy. 2022-06-01; 150: 112994
DOI: 10.1016/j.biopha.2022.112994
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López-Gambero AJ(1), Pacheco-Sánchez B(2), Rosell-Valle C(3), Medina-Vera D(4), Navarro JA(5), Fernández-Arjona MDM(6), de Ceglia M(7), Sanjuan C(8), Simon V(9), Cota D(10), Rivera P(11), Rodríguez de Fonseca F(12), Suárez J(13).
Author information:
(1)Instituto de investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain;
UGC Salud Mental, Hospital Regional Universitario de Málaga, 29010 Málaga,
Spain; Universidad de Málaga, Andalucia Tech, Departamento de Biología Celular,
Genética y Fisiología, Campus de Teatinos s/n, 29071 Málaga, Spain. Electronic
address: .
(2)Instituto de investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain.
Electronic address: .
(3)Instituto de investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain.
Electronic address: .
(4)Instituto de investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain;
Universidad de Málaga, Andalucia Tech, Departamento de Biología Celular,
Genética y Fisiología, Campus de Teatinos s/n, 29071 Málaga, Spain; Universidad
de Málaga, Andalucia Tech, Facultad de Medicina, Campus de Teatinos s/n, 29071
Málaga, Spain; UGC Corazón, Hospital Universitario Virgen de la Victoria, 29010
Málaga, Spain. Electronic address: .
(5)Instituto de investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain;
UGC Salud Mental, Hospital Regional Universitario de Málaga, 29010 Málaga,
Spain; Universidad de Málaga, Andalucia Tech, Facultad de Medicina, Campus de
Teatinos s/n, 29071 Málaga, Spain. Electronic address: .
(6)Instituto de investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain;
UGC Salud Mental, Hospital Regional Universitario de Málaga, 29010 Málaga,
Spain. Electronic address: .
(7)Instituto de investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain;
UGC Salud Mental, Hospital Regional Universitario de Málaga, 29010 Málaga,
Spain. Electronic address: .
(8)EURONUTRA S.L, Parque Tecnológico de Andalucía, Campanillas, 29590, Spain.
Electronic address: .
(9)University of Bordeaux, INSERM, Neurocentre Magendie, U1215, 33000 Bordeaux,
France. Electronic address: .
(10)University of Bordeaux, INSERM, Neurocentre Magendie, U1215, 33000 Bordeaux,
France. Electronic address: .
(11)Instituto de investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain;
UGC Salud Mental, Hospital Regional Universitario de Málaga, 29010 Málaga,
Spain. Electronic address: .
(12)Instituto de investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain;
UGC Salud Mental, Hospital Regional Universitario de Málaga, 29010 Málaga,
Spain. Electronic address: .
(13)Instituto de investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain;
Universidad de Málaga, Andalucia Tech, Facultad de Medicina, Campus de Teatinos
s/n, 29071 Málaga, Spain; Departamento de Anatomía Humana, Medicina Legal e
Historia de la Ciencia, Universidad de Málaga, 29071 Málaga, Spain. Electronic
address: .
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.
Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.