Fibroblast growth factor 2 exacerbates inflammation in adipocytes through NLRP3 inflammasome activation
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Online ISSN 1976-3786 Print ISSN 0253-6269
RESEARCH ARTICLE
Fibroblast growth factor 2 exacerbates inflammation in adipocytes through NLRP3 inflammasome activation De‑Li ZhuGe1,2 · Hafiz Muhammad Ahmad Javaid1 · Namood E. Sahar1 · Ying‑Zheng Zhao2 · Joo Young Huh1
Received: 25 October 2020 / Accepted: 19 November 2020 © The Pharmaceutical Society of Korea 2020
Abstract Chronic inflammation in adipose tissue is the hallmark of obesity and a major risk factor for the development of obesity-induced insulin resistance. NLRP3 inflammasome regulates the maturation and secretion of pro-inflammatory cytokines, such as IL-1β and IL-18, and was recently discovered to be involved in obesity-related metabolic diseases. Fibroblast growth factors (FGFs) such as FGF1, FGF10, and FGF21 are adipokines that regulate adipocyte development and metabolism, but reports on the effect of other FGFs on adipocytes are lacking. In the present study, the novel role of FGF2 in NLRP3 inflammasome activation was elucidated. Our results showed that FGF2 levels were increased during adipocyte differentiation and in the adipose tissue of high-fat diet (HFD)-induced obese mice. Recombinant FGF2 treatment upregulated inflammasome markers such as NLRP3, which was further exaggerated by TNF-ɑ treatment. Interestingly, β-Klotho, a co-receptor of FGF21, was significantly decreased by FGF2 treatment. Results from mice confirmed the positive correlation between FGF2 and NLRP3 expression in epididymal and subcutaneous adipose tissue, while exercise training effectively reversed HFD-induced NLRP3 expression as well as FGF2 levels in both adipose depots. Our results suggest that FGF2 is an adipokine that may exacerbate the inflammatory Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12272-020-01295-2) contains supplementary material, which is available to authorized users. * Joo Young Huh [email protected] 1
College of Pharmacy, Chonnam National University, 77, Yongbong‑ro, Buk‑gu, Gwangju 61186, Republic of Korea
2
College of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China
response in adipocytes through NLRP3 inflammasome activation. Keywords FGF2 · Inflammasome · NLRP3 · Adipocyte · Obesity · Metabolism
Introduction Obesity-related metabolic disorders are becoming one of the most important public health concerns worldwide (Bluher 2019). Between 1975 and 2014, the prevalence of obesity (BMI ≥ 30 kg/m2) rapidly increased from 3.2 to 10.8% in adult men and from 6.4 to 14.9% in adult women (NCD-RisC 2016). Accumulated evidence has shown that obesity was strongly related to the pathogenesis of various diseases, such as atherosclerosis, type 2 diabetes, neurodegenerative diseases, and cancer (Kahn et al. 2006; Rocha and Libby 2009; Pulgaron and Delamater 2014). Obesity is characterized by both the hypertrophy and hyperplasia of adipocytes, accompanied by chronic local inflammation (Klöting and Blüher 2014). In an obese state, adipocytes are prone to secreting pro-inflammatory adipo
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