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

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, ?-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, ?-mangostin mitigated aging-associated adiposity, hyperlipidemia, and insulin resistance. Further study showed that ?-mangostin alleviated aging-related adipose tissue inflammation by reducing macrophage content and shifting pro-inflammatory macrophage polarization. Moreover, ?-mangostin protected the old mice against liver injury through suppressing the secretion of microRNA-155-5p from macrophages. The above results demonstrated that ?-mangostin represents a new scaffold to alleviate adipose tissue inflammation, which might be a novel candidate to treat aging-related metabolic disorders.

SUBMITTER: Li D

PROVIDER: S-EPMC6932911 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Li Dan D Liu Qianyu Q Lu Xiuqiang X Li Zhengqiu Z Wang Chunming C Leung Chung-Hang CH Wang Yitao Y Peng Cheng C Lin Ligen L

Aging 20191206 23

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 (<i>Garcinia mangostana</i>), 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 ...[more]

PMID: 31806859

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Project description:Fat inflammation may play an important role in comorbidities associated with obesity such as atherosclerosis.To first establish feasibility of fat transplantation, epididymal fat pads were harvested from wild-type C57BL/6J mice and transplanted into leptin-deficient (Lep(ob/ob)) mice. Fat transplantation produced physiological leptin levels and prevented obesity and infertility in Lep(ob/ob) mice. However, the transplanted fat depots were associated with chronically increased macrophage infiltration with characteristics identical to those observed in fat harvested from obese animals. The inflammation in transplanted adipose depots was regulated by the same factors that have been implicated in endogenous fat inflammation such as monocyte chemoattractant protein-1. To determine whether this inflamed adipose depot could affect vascular disease in mice, epididymal fat depots were transplanted into atherosclerosis-prone apolipoprotein E-deficient ApoE(-/-) mice. Plasma from ApoE(-/-) mice receiving fat transplants contained increased leptin, resistin, and monocyte chemoattractant protein-1 compared with plasma from sham-operated ApoE(-/-) mice. Furthermore, mice transplanted with visceral fat developed significantly more atherosclerosis compared with sham-operated animals, whereas transplants with subcutaneous fat did not affect atherosclerosis despite a similar degree of fat inflammation. Treatment of transplanted ApoE(-/-) mice with pioglitazone decreased macrophage content of the transplanted visceral fat pad and reduced plasma monocyte chemoattractant protein-1. Importantly, pioglitazone also reduced atherosclerosis triggered by inflammatory visceral fat but had no protective effect on atherosclerosis in the absence of the visceral fat transplantation.Our results indicate that visceral adipose-related inflammation accelerates atherosclerosis in mice. Drugs such as thiazolidinediones might be a useful strategy to specifically attenuate the vascular disease induced by visceral inflammatory fat.

Dataset Information

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

Publications

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

Similar Datasets

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