Abstract

Emerging findings point to a role for brain-derived neurotrophic factor (BDNF) on feeding in mammals. However, its role on energy balance is unclear. Moreover, whether BDNF regulates energy homeostasis in non-mammals remain unknown. This research aimed to determine whether BDNF is a metabolic peptide in zebrafish. Our results demonstrate that BDNF mRNAs and protein, as well as mRNAs encoding its receptors trkb2, p75ntra and p75ntrb, are detectable in the zebrafish brain, foregut and liver. Intraperitoneal injection of BDNF increased food intake at 1, 2 and 6 h post-administration, and caused an upregulation of brain npy, agrp and orexin, foregut ghrelin, and hepatic leptin mRNAs, and a reduction in brain nucb2. Fasting for 7 days increased bdnf and p75ntrb mRNAs in the foregut, while decreased bdnf, trkb2, p75ntra and p75ntrb mRNAs in the brain and liver. Additionally, the expression of bdnf and its receptors increased preprandially, and decreased after a meal in the foregut and liver. Finally, we observed BDNF-induced changes in the expression and/or activity of enzymes involved in glucose and lipid metabolism in the liver. Overall, present results indicate that BDNF is a novel regulator of appetite and metabolism in fish, which is modulated by energy intake and food availability.

Highlights

  • Emerging findings point to a role for brain-derived neurotrophic factor (BDNF) on feeding in mammals

  • But significant levels of bdnf mRNAs were found in the eye, hindgut and spleen, while a minimum expression was detected in the skin, gill, heart, foregut and muscle

  • No evidence is available in fish regarding the existence of such a link between BDNF and the regulation of food intake and energy balance

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Summary

Introduction

Emerging findings point to a role for brain-derived neurotrophic factor (BDNF) on feeding in mammals. Our results demonstrate that BDNF mRNAs and protein, as well as mRNAs encoding its receptors trkb, p75ntra and p75ntrb, are detectable in the zebrafish brain, foregut and liver. Besides TrkB, mammalian BDNF can bind to the p75 neurotrophin receptor (p75NTR), with low-affinity33 While this receptor is present in f­ish, its distribution and mechanisms of actions in this vertebrate group is yet to be explored. Besides the neurotrophic properties of BDNF, emerging findings in mammals have described an important role for this peptide in the regulation of feeding and energy balance [reviewed i­n40–42]. BDNF has been shown to reduce serum levels of non-esterified free fatty acids, total cholesterol and phospholipids, as well as the liver triglyceride content in diabetic m­ ice, which points to a role for the peptide in lipid metabolism as well

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