Research Paper Volume 11, Issue 23 pp 11084—11110

α-Mangostin remodels visceral adipose tissue inflammation to ameliorate age-related metabolic disorders in mice

Dan Li 1, 2, , Qianyu Liu 2, , Xiuqiang Lu 3, , Zhengqiu Li 4, , Chunming Wang 2, , Chung-Hang Leung 2, , Yitao Wang 2, , Cheng Peng 1, , Ligen Lin 2, 5, ,

  • 1 State Key Laboratory of Southwestern Characteristic Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
  • 2 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China
  • 3 Fuqing Branch of Fujian Normal University, Fuzhou, China
  • 4 School of Pharmacy, Jinan University, Guangzhou, China
  • 5 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

received: August 23, 2019 ; accepted: November 18, 2019 ; published: December 6, 2019 ;

https://doi.org/10.18632/aging.102512
How to Cite

Copyright © 2019 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Low-grade chronic adipose tissue inflammation contributes to the onset and development of aging-related insulin resistance and type 2 diabetes. In the current study, α-mangostin, a xanthone isolated from mangosteen (Garcinia mangostana), was identified to ameliorate lipopolysaccharides-induced acute adipose tissue inflammation in mice, by reducing the expression of pro-inflammatory cytokines and chemokines. In a cohort of young (3 months) and old (18–20 months) mice, α-mangostin mitigated aging-associated adiposity, hyperlipidemia, and insulin resistance. Further study showed that α-mangostin alleviated aging-related adipose tissue inflammation by reducing macrophage content and shifting pro-inflammatory macrophage polarization. Moreover, α-mangostin protected the old mice against liver injury through suppressing the secretion of microRNA-155-5p from macrophages. The above results demonstrated that α-mangostin represents a new scaffold to alleviate adipose tissue inflammation, which might be a novel candidate to treat aging-related metabolic disorders.

Abbreviations

ALT: alanine aminotransferase; Arg-1: arginase 1; AST: aspartate aminotransferase; ATMs: adipose tissue macrophages; BAT: brown adipose tissue; Ccl5: C-C motif chemokine ligand 5; Ccl11: C-C motif chemokine ligand 11; CLSs: crown like structures; CM: conditioned media; Cxcl10: C-X-C motif chemokine 10; Cx3cl1: C-X3-C motif chemokine ligand 1; DAPI: 4',6-diamidino-2-phenylindole; eWAT: epididymal white adipose tissue; GTT: glucose tolerance tests; HDL-C: HDL-cholesterol; HOMA-IR: homeostatic model assessment of insulin resistance; iNos: inducible nitric oxide synthase; iWAT: inguinal white adipose tissue; KRB: Krebs-Ringer bicarbonate; LDL-C: LDL-cholesterol; M1: classically activated macrophages; M2: alternatively activated macrophages; α-Man: α-mangostin; Mcp-1: monocyte chemotactic protein-1; miR-155: microRNA-155-5p; miRNAs: microRNAs; Mip-1α: macrophage inflammatory protein 1-α; NO: nitric oxide; PPAR: peroxisome proliferator-activated receptor; SIRT1: sirtuin1; SIRT3: sirtuin3; SVF: stromal vascular fraction; TC: total cholesterol; TG: triglyceride.