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

• Published in: Molecular neurobiology 2023-05, Vol.60 (5), p.2486-2506
• Main Authors: Azbazdar, Yagmur, Poyraz, Yusuf Kaan, Ozalp, Ozgun, Nazli, Dilek, Ipekgil, Dogac, Cucun, Gokhan, Ozhan, Gunes
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biomedical and Life Sciences; Biomedicine; Body weight gain; Brain - metabolism; Brain Injuries - metabolism; Cell activation; Cell Biology; Danio rerio; Diet, High-Fat - adverse effects; Fatty liver; Glial cells; High fat diet; Immunofluorescence; Liver; Liver - metabolism; Liver diseases; Locomotor activity; Mice; Mice, Inbred C57BL; Neurobiology; Neurology; Neurosciences; Non-alcoholic Fatty Liver Disease; Olfactory bulb; Regeneration; Risk factors; Telencephalon; Traumatic brain injury; Wnt protein; Zebrafish; β-Catenin
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-023-03210-4

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.