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High-fat diet feeding triggers a regenerative response in the adult zebrafish brain

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Abstract

Non-alcoholic fatty liver disease (NAFLD) includes a range of liver conditions ranging from excess fat accumulation to liver failure. NAFLD is strongly associated with high-fat diet (HFD) consumption that constitutes a metabolic risk factor. While HFD has been elucidated concerning its several systemic effects, there is little information about its influence on the brain at the molecular level. Here, by using a high-fat diet (HFD)-feeding of adult zebrafish, we first reveal that excess fat uptake results in weight gain and fatty liver. Prolonged exposure to HFD induces a significant increase in the expression of pro-inflammation, apoptosis, and proliferation markers in the liver and brain tissues. Immunofluorescence analyses of the brain tissues disclose stimulation of apoptosis and widespread activation of glial cell response. Moreover, glial activation is accompanied by an initial decrease in the number of neurons and their subsequent replacement in the olfactory bulb and the telencephalon. Long-term consumption of HFD causes activation of Wnt/β-catenin signaling in the brain tissues. Finally, fish fed an HFD induces anxiety, and aggressiveness and increases locomotor activity. Thus, HFD feeding leads to a non-traumatic brain injury and stimulates a regenerative response. The activation mechanisms of a regeneration response in the brain can be exploited to fight obesity and recover from non-traumatic injuries.

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Acknowledgements

We thank Izmir Biomedicine and Genome Center Vivarium-Zebrafish Core Facility and the facility manager Emine Gelinci for providing zebrafish care, Optical Imaging Core Facility and the facility manager Dr. Melek Ucuncu for microscope facility support and Histopathology Core Facility and the facility manager Ece Uzun for her help in ORO staining. We also thank Fadime Oztoprak for her guidance in statistical analysis.

Funding

GO Lab is funded by EMBO Installation Grant (IG 3024). This work has been supported by the Scientific and Technological Research Council of Turkey (TUBITAK, grant number 215Z365). YA was supported by TUBITAK 2211-C Domestic Priority Areas Doctoral Scholarship Program. YKP, DN, and DI were supported by TUBITAK 2210-C Domestic Priority Areas Master’s Scholarship Program.

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GO, YA, and GC designed the experiments. YA, YKP, OO, DN, and DI performed the experiments. YA, YKP, OO, DN, and GC drafted the manuscript. GO wrote the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Gunes Ozhan.

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The animal study protocol was approved by the Animal Experiments Local Ethics Committee of Izmir Biomedicine and Genome Center (IBG-AELEC) (2020–003, 12/02/2020).

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Azbazdar, Y., Poyraz, Y.K., Ozalp, O. et al. High-fat diet feeding triggers a regenerative response in the adult zebrafish brain. Mol Neurobiol 60, 2486–2506 (2023). https://doi.org/10.1007/s12035-023-03210-4

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