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Endocrine Abstracts (2021) 77 P49 | DOI: 10.1530/endoabs.77.P49

SFEBES2021 Poster Presentations Metabolism, Obesity and Diabetes (78 abstracts)

Interplay of NUCB2/Nesfatin-1 and inflammation in white adipose tissue

Seley Gharanei 1,2 , Vanlata Patel 2 , Kiran Shabir 1,2 , Ria Patel 3,2 , Harpal Randeva 1,2 & Ioannis Kyrou 1,2,4,5


1University Hospitals Coventry and Warwickshire, Coventry, United Kingdom; 2University of Warwick, Coventry, United Kingdom; 3Imperial College London, London, United Kingdom; 4Aston University, Birmingham, United Kingdom; 5Coventry University, Coventry, United Kingdom


Background: Excess adipose tissue accumulation and obesity are characterised by a chronic, low-grade, systemic inflammation that contributes to obesity-related cardio-metabolic disease. Nestfatin-1 is a neuropeptide derived from the precursor protein nucleobindin-2 (NUCB2), which was initially reported to exert anorexigenic effects. We have previously shown that NUCB2/Nesfatin-1 is highly expressed in human and mouse subcutaneous white adipose tissue (Sc-WAT) and that circulating nesfatin-1 levels significantly increase upon a high-fat diet (HFD) and in response to inflammation.

Objective: The present study aimed to investigate the effects of a HFD (12 weeks) in NUCB2 knockout (KO) mice and of nesfatin-1 treatment in LPS-stimulated 3T3-L1 cells.

Methods: Sc-WAT samples from wild type (WT) and NUCB2 KO mice that were fed a normal diet (ND) or HFD for 12 weeks were used for RNA and protein extraction, as well as immunohistochemistry. 3T3-L1 cells were also treated with 100nM nesfatin-1 during differentiation and stimulated with 10μg/mL LPS for measuring pro-inflammatory cytokines (mRNA and protein).

Results: Following the 12-week HFD, the mRNA expression of TNFα, IL6, IL1-beta, MCP1, adgre1 and HMGB1 significantly increased in the Sc-WAT of NUCB2 KO mice compared to ND (all p-values <0.05), whereas only IL1-beta, MCP1 and HMGB1 significantly increased in the Sc-WAT of WT mice (all p-values <0.05). Adiponectin and NRF2 expression significantly decreased in the Sc-WAT of HFD-fed NUCB2 KO (all p-values <0.05), without changes in HFD-fed WT mice. NF-kB activation was demonstrated by immunofluorescence and immunoblot in the Sc-WAT of HFD-fed NUCB2 KO mice. Furthermore, nesfatin-1 treatment in LPS-stimulated 3T3-L1 cells significantly reduced the expression of pro-inflammatory cytokines and HMGB1 (all p-values <0.05).

Conclusions: The present findings demonstrate that HFD induces significant inflammation in the Sc-WAT of NUCB2 KO mice, involving HMGB1 and the NRF2 and NF-kB pathways, whilst nesfatin-1 reduces the pro-inflammatory response in LPS-stimulated 3T3-L1 cells.

Volume 77

Society for Endocrinology BES 2021

Edinburgh, United Kingdom
08 Nov 2021 - 10 Nov 2021

Society for Endocrinology 

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