The discovery of candidates for treating metabolic diseases based on adipose tissue remodeling

UM > Institute of Chinese Medical Sciences

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	The discovery of candidates for treating metabolic diseases based on adipose tissue remodeling
	Chen Cheng1 ; Ren Yongmei 2; Zhu Jianzhong1 ; Feng Zheling1 ; Zhang Tian1 ; Ye Yang 2; LIN LIGEN1
	2021-09
Size of Audience	150
Type of Speaker	invited talk
Abstract	Interleukin-1β (IL-1β) is mainly produced by macrophages through NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome, which is considered as the culprit of the inflammatory crosstalk between macrophages and adipocytes. Ainsliadimer C (AC), a disesquiterpenoid isolated from Ainsliaea macrocephala, was found to dose-dependently suppress IL-1β secretion in lipopolysaccharide (LPS) plus ATP-treated THP-1 macrophages, through inhibiting the activation of NLRP3 inflammasome. AC activated the NAD+-dependent deacetylase Sirtuin-1 (SIRT1), resulting in reduced acetylation level of NLRP3. Molecular docking results suggested AC binds to the STAC-binding domain to increase the affinity of the substrate to the catalytic domain of SIRT1. In addition, AC attenuated the inflammatory response in 3T3-L1 adipocytes induced by macrophage-conditioned medium. In LPS-induced acute inflammatory mice, AC treatment suppressed the pro-inflammatory cytokine levels in serum and epididymal white adipose tissue (eWAT), and attenuated macrophage infiltration into eWAT, to mitigate adipose tissue inflammation. Taken together, AC represents a novel scaffold to ameliorate adipose tissue inflammation, which might be a candidate to treat obesity associated metabolic diseases.
Source Publication	13th National Symposium on Natural Organic Chemistry
Conference Place	Xinxiang, Henan, China
Document Type	Presentation
Collection	Institute of Chinese Medical Sciences
Corresponding Author	LIN LIGEN
Affiliation	1.University of Macau 2.Shanghai Institute of Materia Medica
First Author Affilication	University of Macau
Recommended Citation GB/T 7714	Chen Cheng,Ren Yongmei,Zhu Jianzhong,et al. The discovery of candidates for treating metabolic diseases based on adipose tissue remodeling[Z]. 13th National Symposium on Natural Organic Chemistry

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