Characterization of cold‐induced remodelling reveals depot‐specific differences across and within brown and white adipose tissues in mice

Jia, Ru; Luo, Xiaoqin; Wang, Guan; Lin, Caixia; Qiao, Hu; Wang, Nan; Yao, Ting; Barclay, Johanna L.; Whitehead, Jonathan P.; Luo, Xiao; Yan, Jiaqi

doi:10.1111/apha.12688

Cited by 64 publications

(51 citation statements)

References 57 publications

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“…Consistent with this, we observed a significant increase in iBAT microvessel density of Cold mice after 4 days. Interestingly, this timepoint happens to coincide with our recent report, which implies days 4-5 after cold exposure is the cold adapted phase of adipose tissues remodeling [28] . It is tempting to speculate that the induced angiogenesis in iBAT may contribute to the major benefits of the ‘cold adapted’ phase.…”

Section: Discussionsupporting

confidence: 83%

“…We recently reported that the remodeling of eWAT is very modest upon cold exposure [28]. In this study, we also observed that eWAT was relatively non-responsive to cold-induced angiogenesis, indicated by the unaltered numbers of the CD31- and vWF-positive cells.…”

Section: Discussionsupporting

confidence: 68%

“…Several murine studies have shown that acute cold acclimation or β 3 -adrenergic agonists induces pro-angiogenic factors in BAT, whilst prolonged exposure of mice to cold results in activation of angiogenesis in iBAT and sWAT [12, 21, 22, 27]. We have recently reported that the remodeling and browning in BAT and WAT during cold exposure exhibit depot-specific differences [28]. However, it remains elusive to what extent BAT and WAT angiogenesis occurs following cold exposure, and whether it shows any depot-specific differences.…”

Section: Discussionmentioning

confidence: 99%

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Cold Exposure Differentially Stimulates Angiogenesis in BAT and WAT of Mice: Implication in Adrenergic Activation

Luo¹,

Jia²,

Luo

et al. 2017

Cell Physiol Biochem

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Background/Aims: To characterize the temporal profile of cold-induced angiogenesis in brown and white adipose tissues of mice in vivo and the temporal changes of angiogenic factors in primary mice brown (BA) and white adipocytes (WA) treated with β₃-adrenoceptor agonist (CL316,243) in vitro. Methods: 8-week old male C57BL/6J mice were individually housed in conventional cages under cold exposure (4°C) for 1, 2, 3, 4 and 5 days. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous (sWAT) and epididymal white adipose tissues (eWAT) were harvested for immunohistochemical and gene expression analysis. In vitro, primary mice BA and WA treated with or without CL316,243 were harvested for gene expression and protein secretion analysis. Results: A combination of morphological and genetic (Vegfa, Vegfr2, Hif-1α, Pai1 and Pedf) analyses demonstrated depot-specific angiogenesis in response to cold exposure. Upon CL316,243 treatment, angiogenic factors (Vegfa, Vegfr2, Hif-1α, Pai1 and Pedf) and secreted protein VEGFA were transiently increased in both BA and WA. Conclusion: Our results show that iBAT is highly responsive to cold-induced angiogenesis that is mainly supported by sWAT with a lesser extent by eWAT. Moreover, the angiogenesis is a transient process with the angiogenic factors may work in an autocrine/paracrine manner.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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Cold Exposure Differentially Stimulates Angiogenesis in BAT and WAT of Mice: Implication in Adrenergic Activation

Luo¹,

Jia²,

Luo

et al. 2017

Cell Physiol Biochem

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“…Our study showed that both β3-agonist (1mg/kg body weight for 2 days) and cold exposure (4°C for 2 days) led to a robust browning phenotype as well as activating IL-25 signal in scWAT, whereas in eWAT only β3-agonist led to the beige effect and cold exposure did not. Jia R. and colleagues had demonstrated the differential responses to cold-induced changes of UCP1 across discrete BAT and WAT depots, which supported the notion that the effects of short-term cold exposure increased thermogenic capacity of BAT, as well as browning of scWAT and, to a lesser extent and later, eWAT [21]. Therefore, the white-to-brown induction of IL-25 firstly appear in the easily beige scWAT such as inguinal WAT.…”

Section: Discussionmentioning

confidence: 79%

IL-25 induces beige fat to improve metabolic homeostasis via macrophage and innervation

Li¹,

Ma²,

Feng

et al. 2018

Preprint

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33Beige fat dissipates energy and functions as a defense against cold and obesity, 34 but the underlying mechanisms remain unclear. We found that the signaling of 35 interleukin (IL)-25 including its cognate receptor, IL-17 receptor B (IL-17RB), 36 increased in adipose tissue upon cold and β3-adrenoceptor agonist stimulation. induced the browning effect in white adipose tissue (WAT) by releasing 13 and 38 promoting alternative activation of macrophages to regulate innervation, which 39 characterized as tyrosine hydroxylase (TH) up-regulation to produce more 40 catecholamine including norepinephrine. Blockade of IL-4Rα and depletion of 41 macrophages with clodronate-loaded liposomes in vivo significantly impaired the 42 browning of WAT. Obese mice administered with IL-25 were protected from obesity 43 on a high-fat diet and the subsequent metabolic disorders, and the process involved 44 the uncoupling protein 1 (UCP1)-mediated thermogenesis. In conclusion, the 45 activation of IL-25 signaling on beige fat might play a therapeutic potential for 46 obesity and its associated metabolic disorders. 48Introduction 52 53 Obesity, which affects approximately 13% adults worldwide, has become a 54 major and pressing global problem. Obesity increases the risk of various metabolic 55 disorders such as hypertension, type 2 diabetes, cardiovascular diseases and cancer [1]. 56As the high energy-density diet and the sedentary lifestyle cause obesity, interventions 57 have been focused on pathways involving a decrease in energy intake and/or an 58 increase in energy expenditure. Brown adipose tissue (BAT) in neck and interscapular 59 region produces heat and is important for small mammals housed in cold environment. 60 Activation of the uncoupling protein 1 (UCP1)-positive adipocytes would release heat 61 via uncoupled oxidation respiratory chain for ATP synthesis [2]. Therefore, brown 62 adipocytes could be a therapeutic target in the treatment of obesity, although the 63 thermogenic tissue is almost lacking in adults [3]. Besides the classical brown fat, the 64 other thermogenic tissue named beige fat tissue could also be a potential target for 65 treatment of obesity [4]. Although both of the two adipocytes are similar in high 66 expression of UCP1, beige adipocyte differs from classical brown adipocyte in the 67 following characteristics. First, from the perspective of evolution, brown adipocyte 68 derives from a myogenic factor 5 (Myf5) and paired box 7 (Pax7)-positive precursors 69 [5], but beige adipocyte precursors from a Myf5-negative, platelet derived growth 70 factor receptor alpha (Pdgfr-α)-positive cell lineage [6]. Second, beige adipocytes 71 with the browning genes such as Ucp1 and Ppargc1a inducible activated by cold and 72 β-agonist stimulation are mainly located in the subcutaneous and epididymal depot [2, 73 7, 8], while brown adipocytes are located mainly in neck and interscapular region and 74 express high levels of UCP1. Third, the development of brown adipocytes and beige 75 3adipocytes w...

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“…Citations considerably lag behind momentary usage. As can be expected, our top original articles (2015)(2016) in terms of usage have just recently appeared (Ahl et al 2016, de Almeida Faria et al 2016, Jia et al 2016, Rao et al 2016, Vostarek et al 2016. Out of the same manuscript pool, the older 2015 manuscripts collect most citations (Chen et al 2015, Dahl et al 2015, Heimlich et al 2015, Tam et al 2015, Usui et al 2015.…”

mentioning

confidence: 60%

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Persson

2017

Acta Physiologica

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Characterization of cold‐induced remodelling reveals depot‐specific differences across and within brown and white adipose tissues in mice

Cited by 64 publications

References 57 publications

Cold Exposure Differentially Stimulates Angiogenesis in BAT and WAT of Mice: Implication in Adrenergic Activation

Cold Exposure Differentially Stimulates Angiogenesis in BAT and WAT of Mice: Implication in Adrenergic Activation

IL-25 induces beige fat to improve metabolic homeostasis via macrophage and innervation

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