Journal
METABOLITES
Volume 12, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/metabo12040278
Keywords
Alzheimer's disease mouse model; liver inflammation; adipose tissues; gut microbiota; metabolome; PET-CT imaging
Categories
Funding
- JPI-HDHL-INTIMIC Knowledge Platform of Food, Diet, Intestinal Microbiomics, and Human Health [KP-778, 23092/7303/19 MISVILUPPO]
- JPI-HDHL-INTIMIC Joint Transnational Research program [INTIMIC-085 GUTMOM, 946/2019]
- Fund for Scientific Research (FRS-FNRS, Belgium)
- Research Foundation-Flanders (FWO, Belgium)
- INSERM Institut National de la Sante et de la Recherche Medicale (France)
- Federal Ministry of Food and Agriculture (BMEL)
- Ministry of Education, University and Research (MIUR)
- Ministry of agricultural, food, and forestry policies (MiPAAF)
- National Institute of Health (ISS) on behalf of the Ministry of Health (Italy)
- National Institute of Health Carlos III (Spain)
- Netherlands Organisation for Health Research and Development (ZonMw, The Netherlands)
- Austrian Research Promotion Agency (FFG) on behalf of the Austrian Federal Ministry for Education, Science, and Research (BMBWF)
- Ministry of Science and Technology (Israel)
- Formas (Sweden)
- Ministry of Science and Innovation of Spain [ACPIN2017-117, PID2019-108973RB-C22]
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Metabolic impairments and alterations in liver and adipose depots were observed in subjects with Alzheimer's disease (AD), and the gut microbiota may play a modulating role. In a mouse model of AD, we investigated the changes in liver and white/brown adipose tissues and their associations with serum and gut metabolites and gut bacteria. The findings showed impaired lipid accumulation in liver and adipose tissues, along with disrupted gut microbiota profiles.
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 ((18)FDG-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.
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