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

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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.

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MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity.

Hajime Kanda, Sanshiro Tateya, Yoshikazu Tamori … (2006)

Adipocytes secrete a variety of bioactive molecules that affect the insulin sensitivity of other tissues. We now show that the abundance of monocyte chemoattractant protein-1 (MCP-1) mRNA in adipose tissue and the plasma concentration of MCP-1 were increased both in genetically obese diabetic (db/db) mice and in WT mice with obesity induced by a high-fat diet. Mice engineered to express an MCP-1 transgene in adipose tissue under the control of the aP2 gene promoter exhibited insulin resistance, macrophage infiltration into adipose tissue, and increased hepatic triglyceride content. Furthermore, insulin resistance, hepatic steatosis, and macrophage accumulation in adipose tissue induced by a high-fat diet were reduced extensively in MCP-1 homozygous KO mice compared with WT animals. Finally, acute expression of a dominant-negative mutant of MCP-1 ameliorated insulin resistance in db/db mice and in WT mice fed a high-fat diet. These findings suggest that an increase in MCP-1 expression in adipose tissue contributes to the macrophage infiltration into this tissue, insulin resistance, and hepatic steatosis associated with obesity in mice.

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Inflammatory markers in population studies of aging.

Tushar Singh, Anne Newman (2011)

To review findings from major epidemiologic studies regarding risk factors for and consequences of elevated markers of inflammation in older adults. Most large, current epidemiologic studies of older adults have measured serum interleukin-6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-alpha) and some studies also include more extensive batteries of measures including soluble receptors. There are few defined risk factors for the modest elevations in inflammatory markers seen with aging. These include visceral adiposity, lower sex steroid hormones, smoking, depression and periodontal disease. Of the markers assessed, IL-6 is most robustly associated with incident disease, disability and mortality. Though correlated with age, the etiology of elevated inflammatory markers remains incompletely defined. Inflammation, especially IL-6 may be a common cause of multiple age-related diseases or a final common pathway by which disease leads to disability and adverse outcomes in older adults. Future research targeting inflammation should examine these pathways. Copyright © 2011. Published by Elsevier B.V.

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Monocyte chemoattractant protein 1 in obesity and insulin resistance.

Peter Sartipy, David Loskutoff (2003)

This study identifies monocyte chemoattractant protein 1 (MCP-1) as an insulin-responsive gene. It also shows that insulin induces substantial expression and secretion of MCP-1 both in vitro in insulin-resistant (IR) 3T3-L1 adipocytes and in vivo in IR obese mice (ob/ob). Thus, MCP-1 resembles other previously described genes (e.g., PAI-1 and SREBP-1c) that remain sensitive to insulin in IR states. The hyperinsulinemia that frequently accompanies obesity and insulin resistance may therefore contribute to the altered expression of these and other genes in insulin target tissues. In vivo studies also demonstrate that MCP-1 is overexpressed in obese mice compared with their lean controls, and that white adipose tissue is a major source of MCP-1. The elevated MCP-1 may alter adipocyte function because addition of MCP-1 to differentiated adipocytes in vitro decreases insulin-stimulated glucose uptake and the expression of several adipogenic genes (LpL, adipsin, GLUT-4, aP2, beta3-adrenergic receptor, and peroxisome proliferator-activated receptor gamma). These results suggest that elevated MCP-1 may induce adipocyte dedifferentiation and contribute to pathologies associated with hyperinsulinemia and obesity, including type II diabetes.

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Author and article information

Journal

Journal ID (nlm-ta): Aging (Albany NY)

Journal ID (iso-abbrev): Aging (Albany NY)

Journal ID (publisher-id): Aging

Title: Aging (Albany NY)

Publisher: Impact Journals

ISSN (Electronic): 1945-4589

Publication date Collection: 15 December 2019

Publication date (Electronic): 06 December 2019

Volume: 11

Issue: 23

Pages: 11084-11110

Affiliations

[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

Author notes

Correspondence to: Cheng Peng; email: pengchengchengdu@126.com

Correspondence to: Ligen Lin; email: ligenl@um.edu.mo

Article

Publisher ID: 102512 Publisher ID: 102512

DOI: 10.18632/aging.102512

PMC ID: 6932911

PubMed ID: 31806859

SO-VID: b5cb8cc1-ad3d-4763-a76f-24fdea41ced8

License:

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.

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

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GLUT4 biology

Most cited references 50

MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity.

Inflammatory markers in population studies of aging.

Monocyte chemoattractant protein 1 in obesity and insulin resistance.

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