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NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue

  • Seley Gharanei
  • , Manjunath Ramanjaneya
  • , Aaran Hitesh Patel
  • , Vanlata Patel
  • , Kiran Shabir
  • , Callum Auld
  • , Emmanouil Karteris
  • , Ioannis Kyrou*
  • , Harpal Singh Randeva*
  • *Corresponding author for this work
    • Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, CV2 2DX, United Kingdom; Warwick Medical School, University of Warwick, Coventry, CV4 7AL, United Kingdom
    • Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK; Qatar Metabolic Institute, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar; Translational Research Institute, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar
    • Warwick Medical School, University of Warwick, Coventry, CV4 7AL UK.
    • Altnagelvin Hospital, Derry BT47 6SB, UK
    • Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK

    Research output: Contribution to journalArticlepeer-review

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    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.
    Original languageEnglish
    Article number1409
    JournalNutrients
    Volume14
    Issue number7
    DOIs
    Publication statusPublished - 28 Mar 2022

    Bibliographical note

    © 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/).

    UN SDGs

    This output contributes to the following UN Sustainable Development Goals (SDGs)

    1. SDG 3 - Good Health and Well-being
      SDG 3 Good Health and Well-being

    Keywords

    • adipose tissue
    • inflammation
    • nesfatin-1/NUCB2
    • high-fat high-sugar diet
    • obesogenic diet
    • obesity
    • NF-κB
    • HMGB1

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