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.

Asprosin Enhances Cytokine Production by a Co-Culture of Fully Differentiated Mature Adipocytes and Macrophages Leading to the Exacerbation of the Condition Typical of Obesity-Related Inflammation

“…The increase in the concentration of these cytokines is observed in the state of moderate obesity-related inflammation, and their activity is associated with the development of, for example, insulin resistance [ 21 , 22 ]. At the end of last year, Shabir et al [ 24 ] showed that asprosin activates THP-1 macrophages to release TNF-a, IL-12, IL-8, and IL-1b, which may be at least partly related to the TLR4 pathway and NF-kB activation. In turn, the protective effect of asprosin on macrophages was noticed by Zou et al [ 25 ] in an artheriosclerosis model.…”

Asprosin contributes to nonalcoholic fatty liver disease through regulating lipid accumulation and inflammatory response via AMPK signaling

“…43 Furthermore, the proinflammatory effects of Asprosin in a variety of tissues has been reported. 44 For instance, Asprosin has been clarified to exacerbate inflammatory response in pancreatic β-cells. 45 TNF-α, IL-1β, and IL-6 regulated by NF-kappaB p65 are classical proinflammatory mediators related to the development of NAFLD.…”

“…As an initiating factor for NAFLD, aberrant hepatocyte lipid metabolism also contributes to the release of proinflammatory cytokines and inflammatory cell infiltration, further aggravating liver tissue injury 43 . Furthermore, the proinflammatory effects of Asprosin in a variety of tissues has been reported 44 . For instance, Asprosin has been clarified to exacerbate inflammatory response in pancreatic β‐cells 45 .…”

Serum asprosin levels are increased in patients with periodontitis and ST‐segment elevation myocardial infarction and correlated with periodontal parameters: A case–control study

“…16 In addition, asprosin increases PKC-dependent skeletal muscle inflammation brought on by endoplasmic reticulum stress. 17 Because periodontitis has systemic consequences (like other chronic inflammatory illnesses), it might have an effect on the concentration of circulating asprosin. This study's mean periodontal parameter scores revealed highly significant differences between healthy controls vs. periodontitis, healthy controls vs. periodontitis+STEMI, STEMI vs. periodontitis, and STEMI vs. periodontitis+STEMI.…”

“…[13][14][15] According to recent studies, asprosin has a role in the inflammatory reactions of many different cell types. 16,17 To our knowledge, a study examining asprosin levels in periodontitis was not available. Because periodontitis has systemic consequences (like other chronic inflammatory diseases), it affects the levels of circulating asprosin.…”