α-Mangostin ameliorates hepatic steatosis and insulin resistance by inhibition C-C chemokine receptor 2

Kim, Hong Min; Kim, You Mi; Huh, Ji Hye; Lee, Eun Soo; Kwon, Mi Hye; Lee, Bo Ra; Ko, Hyun‐Jeong; Chung, Choon Hee

doi:10.1371/journal.pone.0179204

Cited by 23 publications

(29 citation statements)

References 31 publications

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“…Consistent with the increased expression of serum inflammatory cytokines (such as MCP-1, TNF-α and IL-6) in obese mice, we demonstrated that the expression of CCR2 and macrophage infiltration in SAT and VAT were significantly increased in diet-induced obese mice. This was also observed in other studies of WAT in diet-induced obese rodent models ( Kim et al, 2017 ; Weisberg et al, 2006 ). In vitro, RES inhibited the mRNA and protein expression in CCR2 of THP-1 monocytes ( Cullen et al, 2007 ).…”

Section: Discussionsupporting

confidence: 86%

“…Internal adipose tissue makes up approximately 20% of the total body fat mass and mainly consists of visceral adipose tissue (VAT). In obesity, inflammation can occur due to increased levels of chemokines (such as CCL2 and CXCL1) and inflammatory cytokines (such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6)) secreted from accumulated fat in hepatocytes and adipocytes, causing insulin resistance ( Kim et al, 2017 ; Xu et al, 2003 ). In obesity, macrophage infiltration in adipose tissue was observed in both rodents and humans ( Fjeldborg et al, 2014 ; Harford et al, 2011 ; Michaud et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol reduces the inflammatory response in adipose tissue and improves adipose insulin signaling in high-fat diet-fed mice

Ding

Jiang

Wang

et al. 2018

PeerJ

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BackgroundObesity-induced glucose metabolism disorder is associated with chronic, low-grade, systemic inflammation and is considered a risk factor for diabetes and metabolic syndrome. Resveratrol (RES), a natural anti-inflammatory compound, is observed to improve glucose tolerance and insulin sensitivity in obese rodents and humans. This study aimed to test the effects of RES administration on insulin signaling and the inflammatory response in visceral white adipose tissue (WAT) caused by a high-fat diet (HFD) in mice.MethodsA total of 40 wild-type C57BL/6 male mice were divided into four groups (10 in each group): the standard chow diet (STD) group was fed a STD; the HFD group was fed a HFD; and the HFD-RES/L and HFD-RES/H groups were fed a HFD plus RES (200 and 400 mg/kg/day, respectively). The L and H in RES/L and RES/H stand for low and high, respectively. Glucose tolerance, insulin sensitivity, circulating inflammatory biomarkers and lipid profile were determined. Quantitative PCR and Western blot were used to determine the expression of CC-chemokine receptor 2 (CCR2), other inflammation markers, glucose transporter 4 (GLUT4), insulin receptor substrate 1 (IRS-1) and pAkt/Akt and to assess targets of interest involving glucose metabolism and inflammation in visceral WAT.ResultsHFD increased the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol and proinflammatory cytokines in serum, decreased the high-density lipoprotein cholesterol level in serum, and induced insulin resistance and WAT inflammation in mice. However, RES treatment alleviated insulin resistance, increased the expressions of pAkt, GLUT4 and IRS-1 in WAT, and decreased serum proinflammatory cytokine levels, macrophage infiltration and CCR2 expression in WAT.ConclusionOur results indicated that WAT CCR2 may play a vital role in macrophage infiltration and the inflammatory response during the development of insulin resistance in HFD-induced obesity. These data suggested that administration of RES offers protection against abnormal glucose metabolism and inflammatory adaptations in visceral WAT in mice with HFD-induced obesity.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Resveratrol reduces the inflammatory response in adipose tissue and improves adipose insulin signaling in high-fat diet-fed mice

Ding

Jiang

Wang

et al. 2018

PeerJ

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“…Furthermore, α-MG decreased hepatic steatosis through the hepatic SirT1-AMPK and PPAPγ pathways in obese mice [38]. In addition, it is reported that α-MG ameliorated adipose inflammation and hepatic steatosis in obese C57BL/6 mice receiving a high-fat diet [60], corroborating our findings in this study.…”

Section: Discussionsupporting

confidence: 90%

Crude α-Mangostin Suppresses the Development of Atherosclerotic Lesions in Apoe-Deficient Mice by a Possible M2 Macrophage-Mediated Mechanism

Shibata

Harada‐Shiba

Shibata

et al. 2019

IJMS

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Lifestyle choices play a significant role in the etiology of atherosclerosis. Male Apoe−/− mice that develop spontaneous atherosclerotic lesions were fed 0%, 0.3%, and 0.4% mangosteen extracts, composed largely of α-mangostin (MG), for 17 weeks. Body weight gains were significantly decreased in both MG-treated groups compared to the control, but the general condition remained good throughout the study. The levels of total cholesterol (decreased very-low-density lipoprotein in lipoprotein profile) and triglycerides decreased significantly in the MG-treated mice in conjunction with decreased hepatic HMG-CoA synthase and Fatty acid transporter. Additionally, increased serum lipoprotein lipase activity and histopathology further showed a significant reduction in atherosclerotic lesions at both levels of MG exposure. Real-time PCR analysis for macrophage indicators showed a significant elevation in the levels of Cd163, an M2 macrophage marker, in the lesions of mice receiving 0.4% MG. However, the levels of Nos2, associated with M1 macrophages, showed no change. In addition, quantitative immunohistochemical analysis of macrophage subtypes showed a tendency for increased M2 populations (CD68+/CD163+) in the lesions of mice given 0.4% MG. In further analysis of the cytokine-polarizing macrophage subtypes, the levels of Interleukin13 (Il13), associated with M2 polarization, were significantly elevated in lesions exposed to 0.4% MG. Thus, MG could suppress the development of atherosclerosis in Apoe−/− mice, possibly through an M2 macrophage-mediated mechanism.

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“…As the most important secondary metabolite in the plant, α-MG demonstrates a wide variety of pharmacological effects including anti-inflammation [ 14 , 15 ], anti-oxidant [ 16 ], anti-apoptosis, antibacterial [ 17 ], and anti-Alzheimer’s disease [ 18 ]. α-MG was reported to significantly ameliorate hepatic steatosis in vivo [ 19 , 20 ]. In addition, α-MG was shown to reduce the risk of liver fibrosis on thioacetamide-induced cirrhosis in rats [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Dietary α-Mangostin Provides Protective Effects against Acetaminophen-Induced Hepatotoxicity in Mice via Akt/mTOR-Mediated Inhibition of Autophagy and Apoptosis

Yan

Sun

Ren

et al. 2018

IJMS

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Acetaminophen overdose-induced hepatotoxicity is the most common cause of acute liver failure in many countries. Previously, alpha-mangostin (α-MG) has been confirmed to exert protective effects on a variety of liver injuries, but the protective effect on acetaminophen-induced acute liver injury (ALI) remains largely unknown. This work investigated the regulatory effect and underlying cellular mechanisms of α-MG action to attenuate acetaminophen-induced hepatotoxicity in mice. The increased serum aminotransferase levels and glutathione (GSH) content and reduced malondialdehyde (MDA) demonstrated the protective effect of α-MG against acetaminophen-induced hepatotoxicity. In addition, α-MG pretreatment inhibited increases in tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) caused by exposure of mice to acetaminophen. In liver tissues, α-MG inhibited the protein expression of autophagy-related microtubule-associated protein light chain 3 (LC3) and BCL2/adenovirus E1B protein-interacting protein 3 (BNIP3). Western blotting analysis of liver tissues also proved evidence that α-MG partially inhibited the activation of apoptotic signaling pathways via increasing the expression of Bcl-2 and decreasing Bax and cleaved caspase 3 proteins. In addition, α-MG could in part downregulate the increase in p62 level and upregulate the decrease in p-mTOR, p-AKT and LC3 II /LC3 I ratio in autophagy signaling pathways in the mouse liver. Taken together, our findings proved novel perspectives that detoxification effect of α-MG on acetaminophen-induced ALI might be due to the alterations in Akt/mTOR pathway in the liver.

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α-Mangostin ameliorates hepatic steatosis and insulin resistance by inhibition C-C chemokine receptor 2

Cited by 23 publications

References 31 publications

Resveratrol reduces the inflammatory response in adipose tissue and improves adipose insulin signaling in high-fat diet-fed mice

Resveratrol reduces the inflammatory response in adipose tissue and improves adipose insulin signaling in high-fat diet-fed mice

Crude α-Mangostin Suppresses the Development of Atherosclerotic Lesions in Apoe-Deficient Mice by a Possible M2 Macrophage-Mediated Mechanism

Dietary α-Mangostin Provides Protective Effects against Acetaminophen-Induced Hepatotoxicity in Mice via Akt/mTOR-Mediated Inhibition of Autophagy and Apoptosis

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