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Details

Autor(en) / Beteiligte
Titel
F]GE-180-PET and Post Mortem Marker Characteristics of Long-Term High-Fat-Diet-Induced Chronic Neuroinflammation in Mice
Ist Teil von
  • Biomolecules (Basel, Switzerland), 2023-04, Vol.13 (5)
Ort / Verlag
MDPI AG
Erscheinungsjahr
2023
Link zum Volltext
Quelle
EZB Free E-Journals
Beschreibungen/Notizen
  • Obesity is characterized by immoderate fat accumulation leading to an elevated risk of neurodegenerative disorders, along with a host of metabolic disturbances. Chronic neuroinflammation is a main factor linking obesity and the propensity for neurodegenerative disorders. To determine the cerebrometabolic effects of diet-induced obesity (DIO) in female mice fed a long-term (24 weeks) high-fat diet (HFD, 60% fat) compared to a group on a control diet (CD, 20% fat), we used in vivo PET imaging with the radiotracer [[sup.18]F]FDG as a marker for brain glucose metabolism. In addition, we determined the effects of DIO on cerebral neuroinflammation using translocator protein 18 kDa (TSPO)-sensitive PET imaging with [[sup.18]F]GE-180. Finally, we performed complementary post mortem histological and biochemical analyses of TSPO and further microglial (Iba1, TMEM119) and astroglial (GFAP) markers as well as cerebral expression analyses of cytokines (e.g., Interleukin (IL)-1β). We showed the development of a peripheral DIO phenotype, characterized by increased body weight, visceral fat, free triglycerides and leptin in plasma, as well as increased fasted blood glucose levels. Furthermore, we found obesity-associated hypermetabolic changes in brain glucose metabolism in the HFD group. Our main findings with respect to neuroinflammation were that neither [[sup.18]F]GE-180 PET nor histological analyses of brain samples seem fit to detect the predicted cerebral inflammation response, despite clear evidence of perturbed brain metabolism along with elevated IL-1β expression. These results could be interpreted as a metabolically activated state in brain-resident immune cells due to a long-term HFD.
Sprache
Englisch
Identifikatoren
ISSN: 2218-273X
eISSN: 2218-273X
DOI: 10.3390/biom13050769
Titel-ID: cdi_gale_infotracacademiconefile_A750887691

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