Gharanei, Seley, Ramanjaneya, Manjunath, Patel, Aaran Hitesh, Patel, Vanlata, Shabir, Kiran, Auld, Callum, Karteris, Emmanouil, Kyrou, Ioannis and Randeva, Harpal Singh (2022). NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue. Nutrients, 14 (7),
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.
Publication DOI: | https://doi.org/10.3390/nu14071409 |
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Divisions: | College of Health & Life Sciences > School of Biosciences College of Health & Life Sciences > Aston Medical School |
Additional Information: | © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). |
Uncontrolled Keywords: | adipose tissue,inflammation,nesfatin-1/NUCB2,high-fat high-sugar diet,obesogenic diet,obesity,NF-κB,HMGB1 |
Publication ISSN: | 2072-6643 |
Last Modified: | 06 Dec 2024 08:27 |
Date Deposited: | 08 Apr 2022 10:27 |
Full Text Link: | |
Related URLs: |
https://www.mdp ... -6643/14/7/1409
(Publisher URL) |
PURE Output Type: | Article |
Published Date: | 2022-03-28 |
Accepted Date: | 2022-03-25 |
Authors: |
Gharanei, Seley
Ramanjaneya, Manjunath Patel, Aaran Hitesh Patel, Vanlata Shabir, Kiran Auld, Callum Karteris, Emmanouil Kyrou, Ioannis ( 0000-0002-6997-3439) Randeva, Harpal Singh |