Fibroblast growth factor 2 exacerbates inflammation in adipocytes through NLRP3 inflammasome activation

• Published in: Archives of pharmacal research Vol. 43; no. 12; pp. 1311 - 1324
• Main Authors: ZhuGe, De-Li, Javaid, Hafiz Muhammad Ahmad, Sahar, Namood E., Zhao, Ying-Zheng, Huh, Joo Young
• Format: Journal Article
• Language: English
• Published: Seoul Pharmaceutical Society of Korea 01.12.2020
• Subjects: adipocytes; adipokines; adipose tissue; epididymis; exercise; fibroblast growth factor 2; fibroblasts; high fat diet; inflammasomes; inflammation; insulin resistance; interleukin-18; Medicine; metabolism; obesity; Pharmacology/Toxicology; Pharmacy; Research Article; risk factors; secretion; Adipocyte; Obesity; NLRP3; Inflammasome; Metabolism; FGF2
• ISSN: 0253-6269; 1976-3786; 1976-3786
• DOI: 10.1007/s12272-020-01295-2

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 response in adipocytes through NLRP3 inflammasome activation.