Astrocytes regulate brain fatty acid sensitivity and food intake via cluster of differentiation (CD)36 in diet-induced obesity

COBAN, MUSTAFA MICHAEL. Astrocytes regulate brain fatty acid sensitivity and food intake via cluster of differentiation (CD)36 in diet-induced obesity. 2022, Doctoral Thesis, University of Basel, Faculty of Science.

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Upon high-fat diet (HFD) feeding, exaggerated amounts of saturated fatty acids (FAs) flush the brain and induce a state of “lipotoxicity”, promoting overfeeding and obesity development. Astrocytes actively regulate brain glucose uptake and recently emerged as critical players in homeostatic regulation as well as in the pathophysiology of systemic energy homeostasis.
Here, we demonstrate an increased expression of the FA receptor and transporter cluster of differentiation (CD)36 in glial fibrillary acidic protein (GFAP)-expressing hypothalamic astrocytes upon HFD-induced obesity in mice.
Genetically modified mouse models, brain metabolomics and lipidomics revealed that postnatal CD36 ablation in GFAP-expressing astrocytes in adult mice prevents central FA sensitivity and FA synthesis in diet-induced obese mice. Depletion of CD36 in primary hypothalamic astrocytes in vitro impaired lipid accumulation and mitochondrial oxidative phosphorylation (OXPHOS), possibly via decreased coenzyme Q abundance. This led to an induction of the integrated stress response, especially in the presence of the saturated FA palmitate, mimicking the HFD setting in vitro. Astrocyte-specific CD36 ablation resulted in protection from diet-induced obesity via reduced food intake and a change in food preference towards a low-calorie, normal diet exclusively in obese mice.
Collectively, these experiments reveal an active role of astrocytes in central FA sensitivity via CD36 and that ablation of astrocyte CD36 signaling results in protection from diet-induced obesity.
Advisors:Timper , Katharina and Taylor, Verdon and Konrad, Daniel
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Diabetes Research (Timper)
03 Faculty of Medicine > Departement Biomedizin > Division of Anatomy > Embryology and Stem Cell Biology (Taylor)
UniBasel Contributors:Taylor, Verdon
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:14860
Thesis status:Complete
Number of Pages:v, 91
Identification Number:
  • urn: urn:nbn:ch:bel-bau-diss148608
edoc DOI:
Last Modified:07 Dec 2022 05:30
Deposited On:06 Dec 2022 12:32

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