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@ARTICLE{Mller:258254,
      author       = {Müller, Luisa and Power Guerra, Nicole and Schildt, Anna
                      and Lindner, Tobias and Stenzel, Jan and Behrangi, Newshan
                      and Bergner, Carina and Alberts, Teresa and Bühler, Daniel
                      and Kurth, Jens and Krause, Bernd Joachim and Janowitz,
                      Deborah and Teipel, Stefan and Vollmar, Brigitte and Kuhla,
                      Angela},
      title        = {[18{F}]{GE}-180-{PET} and {P}ost {M}ortem {M}arker
                      {C}haracteristics of {L}ong-{T}erm
                      {H}igh-{F}at-{D}iet-{I}nduced {C}hronic {N}euroinflammation
                      in {M}ice.},
      journal      = {Biomolecules},
      volume       = {13},
      number       = {5},
      issn         = {2218-273X},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DZNE-2023-00600},
      pages        = {769},
      year         = {2023},
      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.},
      keywords     = {Mice / Female / Animals / Diet, High-Fat: adverse effects /
                      Neuroinflammatory Diseases / Obesity: diagnostic imaging /
                      Obesity: metabolism / Carrier Proteins / Neurodegenerative
                      Diseases / Glucose / Positron-Emission Tomography: methods /
                      Mice, Inbred C57BL / TSPO (Other) / [18F]FDG PET/CT (Other)
                      / [18F]GE-180 PET/CT (Other) / diet-induced obesity (Other)
                      / high-fat diet (Other) / neuroinflammation (Other) / GE-180
                      (NLM Chemicals) / Carrier Proteins (NLM Chemicals) / Glucose
                      (NLM Chemicals)},
      cin          = {AG Teipel},
      ddc          = {570},
      cid          = {I:(DE-2719)1510100},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37238638},
      pmc          = {pmc:PMC10216137},
      doi          = {10.3390/biom13050769},
      url          = {https://pub.dzne.de/record/258254},
}