Eosinophils and Type 2 Cytokine Signaling in Macrophages Orchestrate Development of Functional Beige Fat

Qiu, Yifu; Nguyen, Khoa D.; Odegaard, Justin I.; Cui, Xiaojin; Tian, Xiaoyu; Locksley, Richard M.; Palmiter, Richard D.; Chawla, Ajay

doi:10.1016/j.cell.2014.03.066

Cited by 743 publications

(784 citation statements)

References 54 publications

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“…While no changes were detected in the corticosterone levels (Figures S4A and S4B), the type 2 cytokines IL-4, IL-5, and IL-13 were markedly upregulated in both ingSAT and pgVAT of CR mice compared to the AL controls ( Figures 4A, S4C, and S4D). Eosinophils and the type 2 cytokines are sufficient to promote beige fat development through alternative activation of M2 macrophages expressing tyrosine hydroxylase (TH) (Ganeshan and Chawla, 2014;Lee et al, 2015;Martinez et al, 2009;Qiu et al, 2014), rate-limiting enzyme in the catecholamine biosynthesis (Nguyen et al, 2011). Indeed, Th mRNA and TH protein levels were increased in ingSAT and pgVAT in the CR mice ( Figures 4B and S4E).…”

Section: Decreased Caloric Uptake Enhances Type 2 Immune Responsementioning

confidence: 99%

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Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling

et al. 2016

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SUMMARYCaloric restriction (CR) extends lifespan from yeast to mammals, delays onset of age-associated diseases, and improves metabolic health. We show that CR stimulates development of functional beige fat within the subcutaneous and visceral adipose tissue, contributing to decreased white fat and adipocyte size in lean C57BL/6 and BALB/c mice kept at room temperature or at thermoneutrality and in obese leptin-deficient mice. These metabolic changes are mediated by increased eosinophil infiltration, type 2 cytokine signaling, and M2 macrophage polarization in fat of CR animals. Suppression of the type 2 signaling, using Il4ra À/À , Stat6 À/À , or mice transplanted with Stat6 À/À bone marrow-derived hematopoietic cells, prevents the CR-induced browning and abrogates the subcutaneous fat loss and the metabolic improvements induced by CR. These results provide insights into the overall energy homeostasis during CR, and they suggest beige fat development as a common feature in conditions of negative energy balance.

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Section: Decreased Caloric Uptake Enhances Type 2 Immune Responsementioning

confidence: 99%

“…), both models showing impaired type 2 cytokine signaling (Lee et al, 2015;Qiu et al, 2014). The Il4ra À/À animals and their respective controls were on a BALB/c background, while the Stat6 À/À mice were on a C57BL/6J background.…”

Section: Type 2 Immune Signaling Is Necessary For the Browning And Mementioning

confidence: 99%

Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling

et al. 2016

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“…In this context, ATMs are the most intensively studied immune cells of the SVF. They have several functions in endocrine signaling by synthesizing hormones and adipokines that enable interference with insulin-controlled metabolism (Epelman et al 2014;Glass and Olefsky 2012;Lee and Lee 2014;Li et al 2013;Osborn and Olefsky 2012;Qiu et al 2014). The ATMs of the visceral adipose tissue, especially, have prime importance in metabolic regulation (Rosen and Spiegelman 2014).…”

Section: Introductionmentioning

confidence: 99%

Adipose tissue macrophages in non-rodent mammals: a comparative study

et al. 2015

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The stromal vascular fraction (SVF) of adipose tissue in rodents and primates contains mesenchymal stem cells and immune cells. SVF cells have complex metabolic, immune and endocrine functions with biomedical impact. However, in other mammals, the amount of data on SVF stem cells is negligible and whether the SVF hosts immune cells is unknown. In this study, we show that the SVF is rich in immune cells, with a dominance of adipose tissue macrophages (ATMs) in cattle (Bos primigenius taurus), domestic goat (Capra aegagrus hircus), domestic sheep (Ovis aries), domestic cat (Felis catus) and domestic dog (Canis familiaris). ATMs of these species are granulated lysosome-rich cells with lamellipodial protrusions and express the lysosome markers acid phosphatase 5 (ACP-5) and Mac-3/Lamp-2. Using ACP-5 and Mac-3/Lamp-2 as markers, we additionally detected ATMs in other species, such as the domestic horse (Equus ferus caballus), wild boar (Sus scrofa) and red fox (Vulpes vulpes). Feline and canine ATMs also express the murine macrophage marker F4/80 antigen. In the lean condition, the alternative macrophage activation marker CD206 is expressed by feline and canine ATMs and arginase-1 by feline ATMs. Obesity is associated with interleukin-6 and interferon gamma expression and with overt tyrosine nitration in both feline and canine ATMs. This resembles the obesity-induced phenotype switch of murine and human ATMs. Thus, we show, for the first time, that the presence of ATMs is a general trait of mammals. The interaction between the adipose cells and SVF immune cells might be evolutionarily conserved among mammals.

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“…One of the major differences is reliance on type 2 immunity for activation or not [68]. Qiu et al reported that cold exposure is accompanied by elevation of the Th2 cytokines (mainly interleukin 4 from eosinophils), which can readily engage M2 macrophage activation [68].…”

Section: Type 2 Immune Cytokines In Cold-stimulated White Adipose Tissuementioning

confidence: 99%

Adipose Tissue as an Endocrine Organ

Hui¹,

Feng²

2018

Adipose Tissue

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As one of the largest endocrine organs in the body, adipose tissue secrets a number of bioactive hormones, called adipokines. The expression and secretion of adipokines are tightly controlled and coordinated by physiological and pathophysiological conditions. In multiple physiological conditions, such as obesity, cold adaptation, exercise training, expression and secretion of adipokines are altered accordingly, which in turn modulate the metabolism of the whole body in endocrine, paracrine and autocrine manners. The varied changes in adipose tissues are pivotal mediators that aid the body to adapt to various physiological and pathological conditions, whereas almost all obesity-associated diseases are attributable to dysregulation of adipokines.

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Eosinophils and Type 2 Cytokine Signaling in Macrophages Orchestrate Development of Functional Beige Fat

Cited by 743 publications

References 54 publications

Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling

Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling

Adipose tissue macrophages in non-rodent mammals: a comparative study

Adipose Tissue as an Endocrine Organ

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