Nesfatin-1 is the proteolytic cleavage product of Nucleobindin 2, which is
expressed both in a number of brain nuclei (e. g., the paraventricular
nucleus of the hypothalamus) and peripheral tissues. While Nucleobindin 2 acts
as a calcium binding protein, nesfatin-1 was shown to affect energy homeostasis
upon central nervous administration by decreasing food intake and increasing
thermogenesis. In turn, Nucleobindin 2 mRNA expression is downregulated in
starvation and upregulated in the satiated state. Still, knowledge about the
physiological role of endogenous Nucleobindin 2/nesfatin-1 in the
control of energy homeostasis is limited and since its receptor has not yet been
identified, rendering pharmacological blockade impossible. To overcome this
obstacle, we tested and successfully established an antibody-based experimental
model to antagonize the action of nesfatin-1. This model was then employed to
investigate the physiological role of endogenous Nucleobindin
2/nesfatin-1. To this end, we applied nesfatin-1 antibody into the
paraventricular nucleus of satiated rats to antagonize the presumably high
endogenous Nucleobindin 2/nesfatin-1 levels in this feeding condition.
In these animals, nesfatin-1 antibody administration led to a significant
decrease in thermogenesis, demonstrating the important role of endogenous
Nucleobindin 2/nesfatin-1in the regulation of energy expenditure.
Additionally, food and water intake were significantly increased, confirming and
complementing previous findings. Moreover, neuropeptide Y was identified as a
major downstream target of endogenous Nucleobindin 2/nesfatin-1.
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