Fibroblast growth factor 2 exacerbates infl ammation in adipocytes through NLRP3 infl ammasome activation

• Published in: Archives of pharmacal research pp. 1311 - 1324
• Main Authors: De‑Li ZhuGe, Hafiz Muhammad Ahmad Javaid, Namood E. Sahar, Ying‑Zheng Zhao, Joo Young Huh
• Format: Journal Article
• Language: English
• Published: 대한약학회 01.12.2020
• Subjects: 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-020-01295-2

Chronic inflammation in adipose tissue is thehallmark of obesity and a major risk factor for the developmentof obesity-induced insulin resistance. NLRP3inflammasome regulates the maturation and secretion ofpro-inflammatory cytokines, such as IL-1β and IL-18, andwas recently discovered to be involved in obesity-relatedmetabolic diseases. Fibroblast growth factors (FGFs) suchas FGF1, FGF10, and FGF21 are adipokines that regulateadipocyte development and metabolism, but reports on theeffect of other FGFs on adipocytes are lacking. In the presentstudy, the novel role of FGF2 in NLRP3 inflammasome activationwas elucidated. Our results showed that FGF2 levelswere increased during adipocyte differentiation and in theadipose tissue of high-fat diet (HFD)-induced obese mice. Recombinant FGF2 treatment upregulated inflammasomemarkers such as NLRP3, which was further exaggeratedby TNF-ɑ treatment. Interestingly, β-Klotho, a co-receptorof FGF21, was significantly decreased by FGF2 treatment. Results from mice confirmed the positive correlationbetween FGF2 and NLRP3 expression in epididymal andsubcutaneous adipose tissue, while exercise training effectivelyreversed HFD-induced NLRP3 expression as well asFGF2 levels in both adipose depots. Our results suggest thatFGF2 is an adipokine that may exacerbate the inflammatory response in adipocytes through NLRP3 inflammasomeactivation. KCI Citation Count: 14