Zebrafish: A New Promise to Study the Impact of Metabolic Disorders on the Brain

Abstract

Zebrafish has become a popular model to study many physiological and pathophysiological processes in humans. In recent years, it has rapidly emerged in the study of metabolic disorders, namely, obesity and diabetes, as the regulatory mechanisms and metabolic pathways of glucose and lipid homeostasis are highly conserved between fish and mammals. Zebrafish is also widely used in the field of neurosciences to study brain plasticity and regenerative mechanisms due to the high maintenance and activity of neural stem cells during adulthood. Recently, a large body of evidence has established that metabolic disorders can alter brain homeostasis, leading to neuro-inflammation and oxidative stress and causing decreased neurogenesis. To date, these pathological metabolic conditions are also risk factors for the development of cognitive dysfunctions and neurodegenerative diseases. In this review, we first aim to describe the main metabolic models established in zebrafish to demonstrate their similarities with their respective mammalian/human counterparts. Then, in the second part, we report the impact of metabolic disorders (obesity and diabetes) on brain homeostasis with a particular focus on the blood–brain barrier, neuro-inflammation, oxidative stress, cognitive functions and brain plasticity. Finally, we propose interesting signaling pathways and regulatory mechanisms to be explored in order to better understand how metabolic disorders can negatively impact neural stem cell activity.

An Association between Insulin Resistance and Neurodegeneration in Zebrafish Larval Model (Danio rerio)

“…Recent data support the findings of significant pepck expression downregulation at 260 min but not 400 min. Ghaddar and Diotel (2022) reviewed the implications of the zebrafish model of chronic hyperglycemia that could modulate insulin behavior [ 57 ]. Likewise, our zebrafish larval model showed the effects of hyperglycemia.…”

Rapid altitude displacement induce zebrafish appearing acute high altitude illness symptoms

“…Furthermore, the preservation of immune system constituents in farmed zebrafish, coupled with the accessibility of transgenic lines that facilitate in vivo tracking of particular processes within a complete organism [ 22 ]. Recently, zebrafish has become a popular model to study many physiological and pathophysiological processes in humans, especially in the area of oxidative stress [ [23] , [24] , [25] ]. It is worth noting that the gills of zebrafish perform the same gas exchange function as mammalian airways, with a comparable structure featuring a respiratory epithelium coated in mucus, containing immune cells and smooth muscle cells located at the lamellar base.…”

Obesity Impairs Cognitive Function with No Effects on Anxiety-like Behaviour in Zebrafish

“…In the last decade, zebrafish has emerged as a key model organism for behavioural studies [6] and neurological disorders [7,8], as well as for the study of metabolic diseases [9][10][11][12]. This makes zebrafish an interesting model for exploring the effects of energy disruption on behavioural aspects.…”