Impaired brain homeostasis and neurogenesis in diet-induced overweight zebrafish: a preventive role from A. borbonica extract

Abstract

overweight and obesity are worldwide health concerns leading to many physiological disorders. Recent data highlighted their deleterious effects on brain homeostasis and plasticity, but the mechanisms underlying such disruptions are still not well understood. in this study, we developed and characterized a fast and reliable diet-induced overweight (DIO) model in zebrafish, for (1) studying the effects of overfeeding on brain homeostasis and for (2) testing different preventive and/or therapeutic strategies. By overfeeding zebrafish for 4 weeks, we report the disruption of many metabolic parameters reproducing human overweight features including increased body weight, body mass index, fasting blood glucose levels and liver steatosis. Furthermore, DIO fish displayed blood-brain barrier leakage, cerebral oxidative stress, neuroinflammation and decreased neurogenesis. Finally, we investigated the preventive beneficial effects of A. borbonica, an endogenous plant from Reunion island. overnight treatment with A. borbonica aqueous extract during the 4 weeks of overfeeding limited some detrimental central effects of DIO. In conclusion, we established a relevant DIO model in zebrafish demonstrating that overfeeding impairs peripheral and central homeostasis. This work also highlights the preventive protective effects of A. borbonica aqueous extracts in Dio, and opens a way to easily screen drugs aiming at limiting overweight and associated neurological disorders. Obesity and overweight are defined as excessive body weight characterized by body fat accumulation and could be easily estimated by calculating the body mass index (BMI) 1. Both obesity and overweight are among the main health concerns worldwide. Their prevalence is increasing annually in developing and developed countries and has nearly tripled since 1980s according to the World Health Organization (2019). Overweight and obesity are due to an imbalance between energy intake, storage, and expenditure including interactions with hereditary and environmental factors 2-4. They result in numerous metabolic disorders such as dyslipidemia, non-alcoholic fatty liver, hyperglycemia, insulin resistance, and are characterized by chronic inflammation and oxidative stress 5-7. These pathologies lead to many physiological disorders such as cardiovascular complications as well as the development of type 2 diabetes and contribute to increased morbidities 7,8. In addition to impair peripheral metabolism and homeostasis, overweight and obesity could have a negative impact on central nervous system (CNS) homeostasis, leading to cognitive impairments and dementia 9. Such cognitive defects have been reported in many animal models such as in high fat diet (HFD)-treated rodents displaying hippocampal-dependent cognitive impairments 10,11. Among factors contributing to these cognitive dysfunctions, inflammatory and oxidative stress appear as key players leading to blood-brain barrier (BBB) leakage through decreased expression of tight junction proteins in the hippocampus 12. Other studi...

Zebrafish and Flavonoids: Adjuvants against Obesity

“…The Artemia saline diet-induced obese (DIO) zebrafish model was first mentioned in 2010 by the Oka research group and, subsequently, it was reproduced by other research groups. The aforementioned model has also been used to test the effects of some dietary supplement effects on body fat accumulation [ 27 , 59 , 60 , 61 , 62 , 63 ]. DIO zebrafish have subsequently been documented and applied as an induction by overfeeding with commercial feed or through a high calorie diet of corn oil or commercial oil enriched feeds for various obesity study purposes [ 27 , 64 , 65 , 66 ].…”

“…Hyperplasia is regulated by the differentiation of multipotent mesenchymal stem cells into preadipocytes that, under appropriate stimulation, can differentiate terminally into mature adipocytes. These adipocytes are capable to storing excess energy as cytoplasmic neutral lipid droplets of different sizes which can exceed 100 micrometers [ 61 , 89 ]. In this regard, it has been reported that flavonoids have great potential.…”

Caffeic Acid, One of the Major Phenolic Acids of the Medicinal Plant Antirhea borbonica, Reduces Renal Tubulointerstitial Fibrosis

“…More recent data obtained in vivo also highlight a preventive protective effect of A. borbonica aqueous extract in a zebrafish diet-induced overweight model in displaying cerebral oxidative stress and blood-brain barrier leakage [30], as well as in a mouse stroke model [31]. Registration at the French pharmacopeia supposes that the medicinal plants are devoid of toxic effects in humans.…”

HDL biodistribution and brain receptors in zebrafish, using HDLs as vectors for targeting endothelial cells and neural progenitors

“…In addition, in contrast to mammals that have only two main cerebral neurogenic niches during adulthood and a limited capacity to repair the brain, adult zebrafish exhibit numerous neurogenic niches across their brain and an important ability for healing 41 , 44 – 48 . Consequently, more and more studies investigate the impact of metabolic disorders, such as hyperglycemia and obesity, on brain homeostasis and plasticity 29 , 31 , 49 , 50 . However, there are only a few studies concerning HDL receptor expression in zebrafish, in particular in the central nervous system, and no data regarding their potential involvement in brain plasticity and neurogenesis.…”