Deleterious Effects of Overfeeding on Brain Homeostasis and Plasticity in Adult Zebrafish

Overweight and obesity are worldwide epidemic health threats. They recently emerged as disruptors of brain homeostasis leading to a wide variety of neurologic disorders. This study aims at developing a fast and easy overfeeding model using zebrafish for investigating the impact of overweight on brain homeostasis. We established a 4-week overfeeding protocol using commercially available dry food in an ad libitum-like feeding. In the diet-induced obesity/overweight (DIO) fish model, weight, size, and body mass index were increased compared with controls. Also, DIO fish displayed hyperglycemia, and had higher levels of advanced glycation end products and oxidative stress (4-hydroxynonenal [4-HNE]) in a peripheral organ (tail). Although overfed fish did not display major blood-brain barrier leakage, they showed an increased cerebral oxidative stress, blunted brain cell proliferation as well as a striking decreased locomotor activity. Interestingly, switching from an overfeeding to a normal diet partially improved peripheral and central disruptions induced by overfeeding in solely 2 weeks. As a conclusion, this study provides a rapid and easy overfeeding model in zebrafish with relevant peripheral and central disruptions. This model could open the way for further investigations to better understand by which mechanisms overfeeding could disturb brain homeostasis. It also reinforces and contrasts with another zebrafish overweight model, showing that the type of the food provided could impair differently brain homeostasis.