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NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue
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Gharanei, Seley, Ramanjaneya, Manjunath, Patel, Aaran Hitesh, Patel, Vanlata H., Shabir, Kiran, Auld, Callum, Karteris, Emmanouil, Kyrou, Ioannis and Randeva, Harpal S. (2022) NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue. Nutrients, 14 (7). e1409. doi:10.3390/nu14071409 ISSN 2072-6643.
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WRAP-NUCB2-Nesfatin-reduces-obesogenic-diet-induced-inflammation-22.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (3092Kb) | Preview |
Official URL: https://doi.org/10.3390/nu14071409
Abstract
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.
| Item Type: | Journal Article | ||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||||
| SWORD Depositor: | Library Publications Router | ||||||
| Library of Congress Subject Headings (LCSH): | Adipose tissues, Obesity, Diabetes -- Complications, Diet in disease, Diseases -- Animal models, Inflammation | ||||||
| Journal or Publication Title: | Nutrients | ||||||
| Publisher: | MDPI | ||||||
| ISSN: | 2072-6643 | ||||||
| Official Date: | 28 March 2022 | ||||||
| Dates: |
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| Volume: | 14 | ||||||
| Number: | 7 | ||||||
| Article Number: | e1409 | ||||||
| DOI: | 10.3390/nu14071409 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||
| Date of first compliant deposit: | 16 November 2022 | ||||||
| Date of first compliant Open Access: | 16 November 2022 | ||||||
| Related URLs: |
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