Asprosin Exerts Pro-Inflammatory Effects in THP-1 Macrophages Mediated via the Toll-like Receptor 4 (TLR4) Pathway

Abstract

Adipose tissue is a dynamic endocrine organ, secreting a plethora of adipokines which play a key role in regulating metabolic homeostasis and other physiological processes. An altered adipokine secretion profile from adipose tissue depots has been associated with obesity and related cardio-metabolic diseases. Asprosin is a recently described adipokine that is released in response to fasting and can elicit orexigenic and glucogenic effects. Circulating asprosin levels are elevated in a number of cardio-metabolic diseases, including obesity and type 2 diabetes. In vitro studies have reported pro-inflammatory effects of asprosin in a variety of tissues. The present study aimed to further elucidate the role of asprosin in inflammation by exploring its potential effect(s) in THP-1 macrophages. THP-1 monocytes were differentiated to macrophages by 48 h treatment with dihydroxyvitamin D3. Macrophages were treated with 100 nM recombinant human asprosin, 100 ng/mL lipopolysaccharide (LPS), and 10 μM caffeic acid phenethyl ester (CAPE; an inhibitor of NFκB activation) or 1 µM TAK-242 (a Toll-like receptor 4, TLR4, inhibitor). The expression and secretion of pertinent pro-inflammatory mediators were measured by qPCR, Western blot, ELISA and Bioplex. Asprosin stimulation significantly upregulated the expression and secretion of the pro-inflammatory cytokines: tumour necrosis factor α (TNFα), interleukin-1β (IL-1β), IL-8 and IL-12 in vitro. This pro-inflammatory response in THP-1 macrophages was partly attenuated by the treatments with CAPE and was significantly inhibited by TAK-242 treatment. Asprosin-induced inflammation is significantly counteracted by TLR4 inhibition in THP-1 macrophages, suggesting that asprosin exerts its pro-inflammatory effects, at least in part, via the TLR4 signalling pathway.

Publication DOI: https://doi.org/10.3390/ijms24010227
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > Aston Medical School
Additional Information: Copyright © 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/). Funding Information: The authors thank the University Hospitals Coventry and Warwickshire (UHCW) NHS Trust and Aston University for funding support.
Uncontrolled Keywords: Article,asprosin,adipokines,inflammation,THP-1 macrophages,Toll-like receptor 4,TLR4
Publication ISSN: 1422-0067
Last Modified: 21 Feb 2024 08:20
Date Deposited: 10 Jan 2023 10:18
Full Text Link:
Related URLs: https://www.mdp ... 2-0067/24/1/227 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2023-01
Published Online Date: 2022-12-23
Accepted Date: 2022-12-20
Authors: Shabir, Kiran
Gharanei, Seley
Orton, Sophie
Patel, Vanlata
Chauhan, Parbata
Karteris, Emmanouil
Randeva, Harpal S.
Brown, James E.
Kyrou, Ioannis (ORCID Profile 0000-0002-6997-3439)

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