Abstract
Nesfatin-1, a posttranslational product of the protein encoded by the nucleobindin 2 gene (NUCB2), was functionally identified as an appetite regulatory molecule in rat hypothalamic nuclei. In the years following the discovery, those findings have been corroborated and expanded upon, and we now know that nesfatin-1 is expressed throughout peripheral tissues and exerts physiological effects beyond feeding control. Literature indicates that adipose tissue is one of the peripheral sources of NUCB2/nesfatin-1, and in this setting, it has anti-inflammatory effects that have recently been implicated in regulating chronic inflammation associated with diet-induced obesity. Currently, there are gaps in our understanding of what cell types within the adipose tissue compartment respond to nesfatin-1, in addition to the cellular mechanism(s) of this peptide. In this study, we sought to determine a mechanism by which this peptide might directly interact with the immune system starting with a human B cell line, Raji. We show that nesfatin-1 inhibits lipopolysaccharide (LPS) and B cell receptor (BCR) dual stimulation-mediated B cell growth, stimulation induced cell death, and secretion of inflammatory mediators. Specifically, there was a reduced fold-change in B cell growth during stimulation which is paired with a reduction in the formation of apoptotic (annexin Vþ) cells. In addition, nesfatin-1 significantly reduced IgM secretion and modestly reduced TNFa secretion by stimulated B cells. The anti-inflammatory effects of nesfatin-1 overall are likely due to attenuation of NF-κB signaling, via inhibition of IκB degradation, in stimulated B cells.
Recommended Citation
T. L. Steffen et al., "The anorexigenic peptide nesfatin-1 dampens the B cell response to receptor-mediated stimulation through inhibition of NF-kB signaling," American Journal of Physiology, American Physiological Society, Mar 2025.
The definitive version is available at https://doi.org/doi.org/10.1152/ajpregu.00233.2024
Department(s)
Biological Sciences
Publication Status
Open Access
Keywords and Phrases
inflammation; nesfatin-1; NUCB2; obesity; peptide
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2025 The Authors, All rights reserved
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution-Share Alike 4.0 License.
Publication Date
March 26, 2025
PubMed ID
40135734
