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000258254 1001_ $$00000-0001-7942-3273$$aMüller, Luisa$$b0
000258254 245__ $$a[18F]GE-180-PET and Post Mortem Marker Characteristics of Long-Term High-Fat-Diet-Induced Chronic Neuroinflammation in Mice.
000258254 260__ $$aBasel$$bMDPI$$c2023
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000258254 520__ $$aObesity 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.
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000258254 650_7 $$2Other$$aTSPO
000258254 650_7 $$2Other$$a[18F]FDG PET/CT
000258254 650_7 $$2Other$$a[18F]GE-180 PET/CT
000258254 650_7 $$2Other$$adiet-induced obesity
000258254 650_7 $$2Other$$ahigh-fat diet
000258254 650_7 $$2Other$$aneuroinflammation
000258254 650_7 $$2NLM Chemicals$$aGE-180
000258254 650_7 $$2NLM Chemicals$$aCarrier Proteins
000258254 650_7 $$0IY9XDZ35W2$$2NLM Chemicals$$aGlucose
000258254 650_2 $$2MeSH$$aMice
000258254 650_2 $$2MeSH$$aFemale
000258254 650_2 $$2MeSH$$aAnimals
000258254 650_2 $$2MeSH$$aDiet, High-Fat: adverse effects
000258254 650_2 $$2MeSH$$aNeuroinflammatory Diseases
000258254 650_2 $$2MeSH$$aObesity: diagnostic imaging
000258254 650_2 $$2MeSH$$aObesity: metabolism
000258254 650_2 $$2MeSH$$aCarrier Proteins
000258254 650_2 $$2MeSH$$aNeurodegenerative Diseases
000258254 650_2 $$2MeSH$$aGlucose
000258254 650_2 $$2MeSH$$aPositron-Emission Tomography: methods
000258254 650_2 $$2MeSH$$aMice, Inbred C57BL
000258254 7001_ $$00000-0001-6036-7574$$aPower Guerra, Nicole$$b1
000258254 7001_ $$aSchildt, Anna$$b2
000258254 7001_ $$00000-0001-7826-3132$$aLindner, Tobias$$b3
000258254 7001_ $$aStenzel, Jan$$b4
000258254 7001_ $$aBehrangi, Newshan$$b5
000258254 7001_ $$aBergner, Carina$$b6
000258254 7001_ $$aAlberts, Teresa$$b7
000258254 7001_ $$aBühler, Daniel$$b8
000258254 7001_ $$00000-0001-6864-4513$$aKurth, Jens$$b9
000258254 7001_ $$aKrause, Bernd Joachim$$b10
000258254 7001_ $$aJanowitz, Deborah$$b11
000258254 7001_ $$0P:(DE-2719)2000026$$aTeipel, Stefan$$b12$$udzne
000258254 7001_ $$aVollmar, Brigitte$$b13
000258254 7001_ $$aKuhla, Angela$$b14
000258254 770__ $$aNovel Imaging Biomarkers for Brain PET Imaging
000258254 773__ $$0PERI:(DE-600)2701262-1$$a10.3390/biom13050769$$gVol. 13, no. 5, p. 769 -$$n5$$p769$$tBiomolecules$$v13$$x2218-273X$$y2023
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