Perivascular mesenchymal cells control adipose-tissue macrophage accrual in obesity

Shan, Bo; Shao, Mengle; Zhang, Qianbin; Hepler, Chelsea; Paschoal, Vivian A.; Barnes, Spencer; Vishvanath, Lavanya; An, Yu; Lin, Jen‐Der; Malladi, Venkat S.; Strand, Douglas W.; Gupta, Olga T.; Elmquist, Joel K.; Oh, Dayoung; Gupta, Rana K.

doi:10.1038/s42255-020-00301-7

Cited by 65 publications

(55 citation statements)

References 57 publications

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“…This pro‐inflammatory cascade, required for the accumulation and activation of pro‐inflammatory macrophages, is regulated by the zinc‐finger transcriptional regulator, ZFP423, which represses NFκB signaling. These results implicate fibro‐inflammatory progenitors, a cell type that appears similar to AFs in other tissues, as important mediators of obesity‐induced metabolic inflammation 161 …”

Section: Perivascular Immune Cell Interactions In Adipose Tissuementioning

confidence: 76%

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Perivascular stromal cells: Directors of tissue immune niches

Sbierski-Kind

Mroz

Molofsky

2021

Immunological Reviews

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Organs are comprised of diverse non-hematopoietic cells, including epithelial cells that form the internal and external layers of tissue surfaces and barriers, endothelial cells that comprise the blood and lymphatic vasculature, and stromal structural cells. Structural cells are classically thought of as "tissue glue," producing and remodeling extracellular matrix (ECM) and secreting other signals that provide passive support and form to tissues. However, recent findings have highlighted novel roles for structural cells as regulators of tissue immunity. 1 This immunoregulatory function is best studied in secondary lymphoid organs, such as lymph nodes, spleen, and mucosal associated lymphoid tissues, where diverse structural cell subsets regulate the function of adaptive lymphocytes and dendritic cells. [2][3][4][5][6] Not surprisingly, structural cells in non-lymphoid tissues are also critical regulators of both innate and adaptive

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Section: Perivascular Immune Cell Interactions In Adipose Tissuementioning

confidence: 76%

“…These results implicate fibroinflammatory progenitors, a cell type that appears similar to AFs in other tissues, as important mediators of obesity-induced metabolic inflammation. 161…”

Section: Stromal-immune Cross Talk In Obesitymentioning

confidence: 99%

Perivascular stromal cells: Directors of tissue immune niches

Sbierski-Kind

Mroz

Molofsky

2021

Immunological Reviews

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“…Chronic low-grade inflammation of the white adipose tissue (WAT) is a hallmark in obesity. 25 We hypothesized that leucine deprivation would reduce inflammation in the WAT. To test our conjecture, we examined the mRNA expression of pro-inflammatory and antiinflammatory genes in the WAT of C57BL/6J mice fed a leucine-deprivation diet.…”

Section: Leucine Deprivation Attenuates Inflammation and Decreases Macrophage Accumulation In The Watmentioning

confidence: 99%

Activation of GCN2 in macrophages promotes white adipose tissue browning and lipolysis under leucine deprivation

Wang

Xiao

et al. 2021

The FASEB Journal

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We have previously shown that leucine deprivation stimulates browning and lipolysis in white adipose tissue (WAT), which helps to treat obesity. Adipose tissue macrophages (ATMs) significantly influence WAT browning and lipolysis. However, it is unclear whether ATMs are involved in leucine deprivation-induced browning and lipolysis in WAT; the associated signals remain to be elucidated. Here, we investigated the role of ATMs and the possible mechanisms involved in WAT browning and lipolysis under leucine-deprivation conditions. In this study, macrophages were depleted in mice by injecting clodronate-liposomes (CLOD) into subcutaneous white adipose tissues. Then, mice lacking general control nonderepressible 2 kinase (GCN2), which is a sensor of amino acid starvation, specifically in Lyz2-expressing cells, were generated to investigate the changes in leucine deprivation-induced WAT browning and lipolysis. We found leucine deprivation decreased the accumulation and changed the polarization of ATMs. Ablation of macrophages by CLOD impaired WAT browning and lipolysis under leucine-deprivation conditions. Mechanistically, leucine deprivation activated GCN2 signals in macrophages. Myeloid-specific abrogation of GCN2 in mice blocked leucine deprivation-induced browning and lipolysis in WAT. Further analyses revealed that GCN2 activation in macrophages reduced the expression of monoamine oxidase A (MAOA), resulting in increased norepinephrine (NE) secretion from macrophages to adipocytes, and this resulted in enhanced WAT browning and lipolysis. Moreover, the injection of CL316,243, a β3-adrenergic receptor agonist, and inhibition of MAOA effectively increased the level of NE, leading to the enhancement of browning and lipolysis of WAT in myeloid GCN2 knockout mice under leucine deprivation. Collectively, our results demonstrate a novel 2 of 16 | WANG et Al.

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“…, IL-6, Ccl2, Cxcl2, Cxcl10) and extracellular matrix components ( e.g. , Col1a1, Col3a1), causing adipose tissue inflammation ( Figure 3 ) ( 98 – 100 ). In human and mouse, CXCL1 + mesothelial cells (CD45 - CD31 − Ter119 − CD41 − PDPN +/− ) recruit neutrophils into the FALC via protein arginine deiminase 4 during peritonitis and promote the aggregation of neutrophils, providing first layer of immunological defense in vWAT ( 101 ).…”

Section: The Novel Roles Of Adipose Stem Cells In the Regulation Of Amentioning

confidence: 99%

“…It has been shown that ASCs would be the key cell type that explains distinct inflammatory patterns between sWAT and vWAT in obesity ( Figure 3 ) ( 100 , 103 , 104 ). In obese mice, vWAT shows the higher number of infiltrated macrophages and crown-like structures, whereas sWAT is less prone to inflammation.…”

Section: The Novel Roles Of Adipose Stem Cells In the Regulation Of Amentioning

confidence: 99%

Adipocytes Are the Control Tower That Manages Adipose Tissue Immunity by Regulating Lipid Metabolism

et al. 2021

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Accumulating evidence reveals that adipose tissue is an immunologically active organ that exerts multiple impacts on the regulation of systemic energy metabolism. Adipose tissue immunity is modulated by the interactions between adipocytes and various immune cells. Nevertheless, the underlying mechanisms that control inter-cellular interactions between adipocytes and immune cells in adipose tissue have not been thoroughly elucidated. Recently, it has been demonstrated that adipocytes utilize lipid metabolites as a key mediator to initiate and mediate diverse adipose tissue immune responses. Adipocytes present lipid antigens and secrete lipid metabolites to determine adipose immune tones. In addition, the interactions between adipocytes and adipose immune cells are engaged in the control of adipocyte fate and functions upon metabolic stimuli. In this review, we discuss an integrated view of how adipocytes communicate with adipose immune cells using lipid metabolites. Also, we briefly discuss the newly discovered roles of adipose stem cells in the regulation of adipose tissue immunity.

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Perivascular mesenchymal cells control adipose-tissue macrophage accrual in obesity

Cited by 65 publications

References 57 publications

Perivascular stromal cells: Directors of tissue immune niches

Perivascular stromal cells: Directors of tissue immune niches

Activation of GCN2 in macrophages promotes white adipose tissue browning and lipolysis under leucine deprivation

Adipocytes Are the Control Tower That Manages Adipose Tissue Immunity by Regulating Lipid Metabolism

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