Liver and White/Brown Fat Dystrophy Associates with Gut Microbiota and Metabolomic Alterations in 3xTg Alzheimer’s Disease Mouse Model(39 views) Guzzardi MA, La Rosa F, Campani D, Collado MC, Monleon D, Cacciato Insilla A, Tripodi M, Zega A, Dattilo A, Brunetto MR, Maffei M, Bonino F, Iozzo P
Metabolites (ISSN: 2218-1989electronic), 2022 Mar 22; 12
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Institute of Clinical Physiology, National Research Council (CNR), 56124 Pisa, Italy
larosa.fed@gmail.com (F.L.R.)
maria.t@email.it (M.T.)
alessandro.zega@ifc.cnr.it (A.Z.)
m.maffei@ifc.cnr.it (M.M.)
patricia.iozzo@ifc.cnr.it (P.I.)
Department of Surgical, Medical, Molecular Pathology and Critical Care Medicine, Division of Pathology, Pisa University Hospital, 56124 Pisa, Italy
daniela.campani@unipi.it (D.C.)
andrea.cacciatoinsilla@gmail.com (A.C.I.)
Institute of Agrochemistry and Food Technology-National Research Council (IATA-CSIC), 46980 Valencia, Spain
Faculty of Medicine, Health Research Institute INCLIVA/CIBERFES for Frailty and Healthy Aging, University of Valencia, 46003 Valencia, Spain
daniel.monleon@uv.es
Scuola Superiore Sant’Anna, 56127 Pisa, Italy
a.dattilo@santannapisa.it
Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy
maurizia.brunetto@unipi.it
Institute of Biostructure and Bioimaging (IBB), National Research Council (CNR), 80145 Napoli, Italy
ferruccio.bonino@unipi.it
References: Not available.
Liver and White/Brown Fat Dystrophy Associates with Gut Microbiota and Metabolomic Alterations in 3xTg Alzheimer’s Disease Mouse Model
Metabolic impairments and liver and adipose depots alterations were reported in subjects with Alzheimer’s disease (AD), highlighting the role of the liver–adipose–tissue–brain axis in AD pathophysiology. The gut microbiota might play a modulating role. We investigated the alterations to the liver and white/brown adipose tissues (W/BAT) and their relationships with serum and gut metabolites and gut bacteria in a 3xTg mouse model during AD onset (adulthood) and progression (aging) and the impact of high-fat diet (HFD) and intranasal insulin (INI). Glucose metabolism (18FDG-PET), tissue radiodensity (CT), liver and W/BAT histology, BAT-thermogenic markers were analyzed. 16S-RNA sequencing and mass-spectrometry were performed in adult (8 months) and aged (14 months) 3xTg-AD mice with a high-fat or control diet. Generalized and HFD resistant deficiency of lipid accumulation in both liver and W/BAT, hypermetabolism in WAT (adulthood) and BAT (aging), abnormal cytokine–hormone profiles, and liver inflammation were observed in 3xTg mice; INI could antagonize all these alterations. Specific gut microbiota–metabolome profiles correlated with a significant disruption of the gut–microbiota–liver–adipose axis in AD mice. In conclusion, fat dystrophy in liver and adipose depots contributes to AD progression, and associates with altered profiles of the gut microbiota, which candidates as an appealing early target for preventive intervention.
Liver and White/Brown Fat Dystrophy Associates with Gut Microbiota and Metabolomic Alterations in 3xTg Alzheimer’s Disease Mouse Model