MCP-1 deficiency enhances browning of adipose tissue via increased M2 polarization

Rajasekaran, Monisha; Sul, Ok-Joo; Choi, Eun‐Kyung; Kim, Jieun; Suh, Jae-Hee; Choi, Hye‐Seon

doi:10.1530/joe-19-0190

Cited by 32 publications

(28 citation statements)

References 17 publications

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“…This latter finding is in conceptual agreement with our results suggesting that CCL2 could be a negative regulator of Arg-1 expression and M2 polarization and that a reduction in astrocyte-derived CCL2 secretion in response to ODN 2088 treatment facilitates Arg-1 expression. A link between CCL2 deficiency and increased expression of genes that code for M2 markers, including Arg-1, has also been reported in transgenic mice [46], whereas abrogation of CCL2 fostered M2 polarization and hindered the M1 polarization of adipose tissue macrophages [71]. These studies further support the notion that CCL2 is a negative regulator of M2 phenotype.…”

Section: Polarization Of Macrophages: Role Of Chemokinessupporting

confidence: 69%

Astroglial TLR9 antagonism promotes chemotaxis and alternative activation of macrophages via modulation of astrocyte-derived signals: implications for spinal cord injury

Heary

et al. 2020

J Neuroinflammation

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Background: The recruitment of immune system cells into the central nervous system (CNS) has a profound effect on the outcomes of injury and disease. Glia-derived chemoattractants, including chemokines, play a pivotal role in this process. In addition, cytokines and chemokines influence the phenotype of infiltrating immune cells. Depending on the stimuli present in the local milieu, infiltrating macrophages acquire the classically activated M1 or alternatively activated M2 phenotypes. The polarization of macrophages into detrimental M1 versus beneficial M2 phenotypes significantly influences CNS pathophysiology. Earlier studies indicated that a toll-like receptor 9 (TLR9) antagonist modulates astrocytederived cytokine and chemokine release. However, it is not known whether these molecular changes affect astrocyteinduced chemotaxis and polarization of macrophages. The present studies were undertaken to address these issues. Methods: The chemotaxis and polarization of mouse peritoneal macrophages by spinal cord astrocytes were evaluated in a Transwell co-culture system. Arrays and ELISA were utilized to quantify chemokines in the conditioned medium (CM) of pure astrocyte cultures. Immunostaining for M1-and M2-specific markers characterized the macrophage phenotype. The percentage of M2 macrophages at the glial scar was determined by stereological approaches in mice sustaining a mid-thoracic spinal cord contusion injury (SCI) and intrathecally treated with oligodeoxynucleotide 2088 (ODN 2088), the TLR9 antagonist. Statistical analyses used two-tailed independent-sample t-test and one-way analysis of variance (ANOVA) followed by Tukey's post hoc test. A p value < 0.05 was considered to be statistically significant. Results: ODN 2088-treated astrocytes significantly increased the chemotaxis of peritoneal macrophages via release of chemokine (C-C motif) ligand 1 (CCL1). Vehicle-treated astrocytes polarized macrophages into the M2 phenotype and ODN 2088-treated astrocytes promoted further M2 polarization. Reduced CCL2 and CCL9 release by astrocytes in response to ODN 2088 facilitated the acquisition of the M2 phenotype, suggesting that CCL2 and CCL9 are negative regulators of M2 polarization. The percentage of M2 macrophages at the glial scar was higher in mice sustaining a SCI and receiving ODN 2088 treatment as compared to vehicle-treated injured controls. Conclusions: TLR9 antagonism could create a favorable environment during SCI by supporting M2 macrophage polarization and chemotaxis via modulation of astrocyte-to-macrophage signals.

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Section: Polarization Of Macrophages: Role Of Chemokinessupporting

confidence: 69%

Astroglial TLR9 antagonism promotes chemotaxis and alternative activation of macrophages via modulation of astrocyte-derived signals: implications for spinal cord injury

Heary

et al. 2020

J Neuroinflammation

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“…Recent findings have demonstrated that browning of WAT and BAT activity is affected by immune cells and M2 macrophages, along with eosinophils and group 2 innate lymphoid cells (Villarroya, Cereijo, Villarroya, Gavaldà-Navarro, & Giralt, 2018). WAT browning and increased BAT activity are augmented by recruitment of M2 macrophages upon cold exposure (Qiu et al, 2014) or MCP-1 deficiency (Rajasekaran et al, 2019), whereas M2 polarization upon calorie F I G U R E 4 E 2 decreases ROS level via enhanced HO-1 to upregulate M2 polarization. BMMs were prepared and further incubated with M-CSF (30 ng/ml) for 6 days.…”

Section: Discussionmentioning

confidence: 99%

“…I G U R E 2 (Continued)3.3 | AT browning is increased by M2 macrophage that is upregulated by exogenous E 2In AT, infiltrating monocytes are differentiated into macrophages with specialized functional phenotypes according to the local microenvironment. Recent findings by us and others have reported that WAT browning is induced via M2 polarization, suggesting a substantial contribution of macrophages to browning(Hui et al, 2015;Liu et al, 2015;Rajasekaran et al, 2019;Suárez-Zamorano et al, 2015). Since our previous results demonstrated that gonadal fat from OVX mice exhibits an increased expression of CD11cF4/80, a marker for M1 polarization, as well as decreased expression of CD206F4/80, a marker for M2 polarization(Choi et al, 2015), we examined whether E 2 injection recovers M2 polarization decreased by OVX.…”

mentioning

confidence: 93%

Estrogen enhances browning in adipose tissue by M2 macrophage polarization via heme oxygenase‐1

Sul

Hyun

Rajasekaran

et al. 2020

Journal Cellular Physiology

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Loss of ovarian function results in increased fat mass, leading to the accumulation of adipose tissue macrophages that participate in chronic inflammation. We hypothesized that ovariectomy (OVX)-induced increases in body weight and fat mass are associated with decreased adipose tissue (AT) browning due to estrogen (E 2) deficiency. In mice, OVX decreased AT browning along with increased body weight, fat mass, and size of lipid droplets 12 weeks after surgery. Exogenous E 2 recovered the OVX-induced changes. AT browning was enhanced by M2 macrophages induced by exogenous E 2. E 2-induced M2 polarization occurred due to the increased expression of heme oxygenase-1 (HO-1) in macrophages, leading to decreased reactive oxygen species levels. Collectively, we demonstrated that E 2 enhances AT browning via M2 polarization mediated by HO-1.

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“…Several molecules and pathways have been reported to be involved in white-to-brown adipose tissue conversion. To name a few, MCP-1 30 , IEX-1 31 , Notch signaling 32 , FGF21 33 , melatonin 34 . However, the browning of adipose tissue was accompanied with adverse effects that would facilitate the metabolic dysfunction seen during hypermetabolic conditions 35 .…”

Section: Discussionmentioning

confidence: 99%

Brown adipose tissue-derived exosomes mitigate the metabolic syndrome in high fat diet mice

Zhou

et al. 2020

Theranostics

105

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The ever-increasing incidence of obesity and related disorders impose serious challenges on public health worldwide. Brown adipose tissue (BAT) has strong capacity for promoting energy expenditure and has shown great potential in treating obesity. Exosomes are nanovesicles that share the characteristics of their donor cells. Whether BAT derived exosomes (BAT-Exos) might exert similar metabolic benefits on obesity is worthy of investigation. Methods: Obese mice were established by high-fat-diet (HFD) feeding and were treated with Seum-Exos or BAT-Exos isolated from young healthy mice. Blood glucose, glucose tolerance and blood lipids were tested in mice with indicated treatments. Histology examinations were performed on adipose tissue, liver and heart by HE staining and/or Oil Red O staining. Echocardiography was performed to evaluate cardiac function of mice. In vivo distribution of exosomes was analyzed by fluorescence labeling and imaging and in vitro effects of exosomes were evaluated by cell metabolism analysis. Protein contents of BAT-Exos were analyzed by mass spectrometry. Results: The results showed that BAT-Exos reduced the body weight, lowered blood glucose and alleviated lipid accumulation in HFD mice independently of food intake. Echocardiography revealed that the abnormal cardiac functions of HFD mice were significantly restored after treatment with BAT-Exos. Cell metabolism analysis showed that treatment with BAT-Exos significantly promoted oxygen consumption in recipient cells. Protein profiling of exosomes demonstrated that BAT-Exos were rich in mitochondria components and involved in catalytic processes. Conclusions: Collectively, our study showed that BAT-Exos significantly mitigated the metabolic syndrome in HFD mice. Detailed elucidation of the reactive molecules and mechanism of action would provide new insights in combating obesity and related disorders.

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MCP-1 deficiency enhances browning of adipose tissue via increased M2 polarization

Cited by 32 publications

References 17 publications

Astroglial TLR9 antagonism promotes chemotaxis and alternative activation of macrophages via modulation of astrocyte-derived signals: implications for spinal cord injury

Astroglial TLR9 antagonism promotes chemotaxis and alternative activation of macrophages via modulation of astrocyte-derived signals: implications for spinal cord injury

Estrogen enhances browning in adipose tissue by M2 macrophage polarization via heme oxygenase‐1

Brown adipose tissue-derived exosomes mitigate the metabolic syndrome in high fat diet mice

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