Journal Article

DZNE-2023-00600

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png [18F]GE-180-PET and Post Mortem Marker Characteristics of Long-Term High-Fat-Diet-Induced Chronic Neuroinflammation in Mice.

Müller, L. ; Power Guerra, N. ; Schildt, A. ; Lindner, T. ; Stenzel, J. ; Behrangi, N. ; Bergner, C. ; Alberts, T. ; Bühler, D. ; Kurth, J. ; Krause, B. J. ; Janowitz, D. ; Teipel, S.DZNE* ; Vollmar, B. ; Kuhla, A.

2023
MDPI Basel

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Please use a persistent id in citations: doi:10.3390/biom13050769

Abstract: 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 [18F]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 [18F]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 [18F]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.

Keyword(s): Mice (MeSH) ; Female (MeSH) ; Animals (MeSH) ; Diet, High-Fat: adverse effects (MeSH) ; Neuroinflammatory Diseases (MeSH) ; Obesity: diagnostic imaging (MeSH) ; Obesity: metabolism (MeSH) ; Carrier Proteins (MeSH) ; Neurodegenerative Diseases (MeSH) ; Glucose (MeSH) ; Positron-Emission Tomography: methods (MeSH) ; Mice, Inbred C57BL (MeSH) ; TSPO ; [18F]FDG PET/CT ; [18F]GE-180 PET/CT ; diet-induced obesity ; high-fat diet ; neuroinflammation ; GE-180 ; Carrier Proteins ; Glucose

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Contributing Institute(s):

1. Clinical Dementia Research Rostock /Greifswald (AG Teipel)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2023

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