Cargando…
NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue
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 i...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9003550/ https://www.ncbi.nlm.nih.gov/pubmed/35406022 http://dx.doi.org/10.3390/nu14071409 |
_version_ | 1784686156526387200 |
---|---|
author | Gharanei, Seley Ramanjaneya, Manjunath Patel, Aaran Hitesh Patel, Vanlata Shabir, Kiran Auld, Callum Karteris, Emmanouil Kyrou, Ioannis Randeva, Harpal Singh |
author_facet | Gharanei, Seley Ramanjaneya, Manjunath Patel, Aaran Hitesh Patel, Vanlata Shabir, Kiran Auld, Callum Karteris, Emmanouil Kyrou, Ioannis Randeva, Harpal Singh |
author_sort | Gharanei, Seley |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9003550 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90035502022-04-13 NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue Gharanei, Seley Ramanjaneya, Manjunath Patel, Aaran Hitesh Patel, Vanlata Shabir, Kiran Auld, Callum Karteris, Emmanouil Kyrou, Ioannis Randeva, Harpal Singh Nutrients Article 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. MDPI 2022-03-28 /pmc/articles/PMC9003550/ /pubmed/35406022 http://dx.doi.org/10.3390/nu14071409 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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/). |
spellingShingle | Article Gharanei, Seley Ramanjaneya, Manjunath Patel, Aaran Hitesh Patel, Vanlata Shabir, Kiran Auld, Callum Karteris, Emmanouil Kyrou, Ioannis Randeva, Harpal Singh NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue |
title | NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue |
title_full | NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue |
title_fullStr | NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue |
title_full_unstemmed | NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue |
title_short | NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue |
title_sort | nucb2/nesfatin-1 reduces obesogenic diet induced inflammation in mice subcutaneous white adipose tissue |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9003550/ https://www.ncbi.nlm.nih.gov/pubmed/35406022 http://dx.doi.org/10.3390/nu14071409 |
work_keys_str_mv | AT gharaneiseley nucb2nesfatin1reducesobesogenicdietinducedinflammationinmicesubcutaneouswhiteadiposetissue AT ramanjaneyamanjunath nucb2nesfatin1reducesobesogenicdietinducedinflammationinmicesubcutaneouswhiteadiposetissue AT patelaaranhitesh nucb2nesfatin1reducesobesogenicdietinducedinflammationinmicesubcutaneouswhiteadiposetissue AT patelvanlata nucb2nesfatin1reducesobesogenicdietinducedinflammationinmicesubcutaneouswhiteadiposetissue AT shabirkiran nucb2nesfatin1reducesobesogenicdietinducedinflammationinmicesubcutaneouswhiteadiposetissue AT auldcallum nucb2nesfatin1reducesobesogenicdietinducedinflammationinmicesubcutaneouswhiteadiposetissue AT karterisemmanouil nucb2nesfatin1reducesobesogenicdietinducedinflammationinmicesubcutaneouswhiteadiposetissue AT kyrouioannis nucb2nesfatin1reducesobesogenicdietinducedinflammationinmicesubcutaneouswhiteadiposetissue AT randevaharpalsingh nucb2nesfatin1reducesobesogenicdietinducedinflammationinmicesubcutaneouswhiteadiposetissue |