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Title: | NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue |
Authors: | Gharanei, S Ramanjaneya, M Patel, AH Patel, V Shabir, K Auld, C Karteris, E Kyrou, I Randeva, HS |
Keywords: | adipose tissue;inflammation;nesfatin-1/NUCB2;high-fat high-sugar diet;obesogenic diet;obesity;NF-κB;HMGB1 |
Issue Date: | 28-Mar-2022 |
Publisher: | MDPI AG |
Citation: | Gharanei, S., Ramanjaneya, M., Patel, A.H., Patel. V, Shabir, K., Auld, C., Karteris, E. Kyrou, I. and Randeva, H.S. (2022) 'NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue', Nutrients, 2022, 14 (7), 1409, pp. 1-17. doi: 10.3390/nu14071409. |
Abstract: | Copyright: © 2022 by the authors. Background: Excess adipose tissue accumulation and obesity are characterised by chronic, low-grade, systemic inflammation. Nestfatin-1 is a neuropeptide derived from the precursor protein nucleobindin-2 (NUCB2), which was initially reported to exert anorexigenic effects. The present study aimed to investigate the effects of an obesogenic diet (OD; high-fat, high-sugar) in NUCB2 knockout (KO) mice and of nesfatin-1 treatment in LPS-stimulated 3T3-L1 preadipocytes. Methods: Subcutaneous white adipose tissue (Sc-WAT) samples from wild type (WT) and NUCB2 KO mice that were fed a normal diet (ND), or the OD for 12 weeks were used for RNA and protein extraction, as well as immunohistochemistry. 3T3-L1 cells were treated with 100 nM nesfatin-1 during differentiation and stimulated with 1 µg/mL LPS for measuring the expression and secretion of pro-inflammatory mediators by qPCR, western blotting, immunofluorescence, Bioplex, and ELISA. Results: Following the OD, the mRNA, protein and cellular expression of pro-inflammatory mediators (Tnfα, Il-6, Il-1β, Adgre1, Mcp1, TLR4, Hmbgb1 and NF-kB) significantly increased in the ScWAT of NUCB2 KO mice compared to ND controls. Adiponectin and Nrf2 expression significantly decreased in the ScWAT of OD-fed NUCB2 KO, without changes in the OD-fed WT mice. Furthermore, nesfatin-1 treatment in LPS-stimulated 3T3-L1 cells significantly reduced the expression and secretion of pro-inflammatory cytokines (Tnfα, Il-6, Il-1β, Mcp1) and hmgb1. Conclusion: An obesogenic diet can induce significant inflammation in the ScWAT of NUCB2 KO mice, involving the HMGB1, NRF2 and NF-kB pathways, while nesfatin-1 reduces the pro-inflammatory response in LPS-stimulated 3T3-L1 cells. These findings provide a novel insight into the metabolic regulation of inflammation in WAT. |
Description: | Data Availability Statement: Data are available via the corresponding authors upon reasonable request that does not raise any ethical, privacy, or security concerns. |
URI: | https://bura.brunel.ac.uk/handle/2438/24492 |
DOI: | https://doi.org/10.3390/nu14071409 |
Other Identifiers: | 1409 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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