Myeloid adrenergic signaling via CaMKII forms a feedforward loop of catecholamine biosynthesis

Type 2 immune response has been shown to facilitate cold-induced thermogenesis and browning of white fat. However, whether alternatively activated macrophages produce catecholamine and substantially promote adaptive thermogenesis in adipose tissue remains controversial. Here, we show that tyrosine h...

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Publié dans:J Mol Cell Biol
Auteurs principaux: Luo, Yan, Liu, Bilian, Yang, Xin, Ma, Xiaoxiao, Zhang, Xing, Bragin, Denis E, Yang, Xuexian O, Huang, Wendong, Liu, Meilian
Format: Artigo
Langue:Inglês
Publié: Oxford University Press 2017
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Original Article
Accès en ligne:https://ncbi.nlm.nih.gov/pmc/articles/PMC5907839/
https://ncbi.nlm.nih.gov/pubmed/29087480
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1093/jmcb/mjx046
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spelling pubmed-59078392018-10-01 Myeloid adrenergic signaling via CaMKII forms a feedforward loop of catecholamine biosynthesis Luo, Yan Liu, Bilian Yang, Xin Ma, Xiaoxiao Zhang, Xing Bragin, Denis E Yang, Xuexian O Huang, Wendong Liu, Meilian J Mol Cell Biol Original Article Type 2 immune response has been shown to facilitate cold-induced thermogenesis and browning of white fat. However, whether alternatively activated macrophages produce catecholamine and substantially promote adaptive thermogenesis in adipose tissue remains controversial. Here, we show that tyrosine hydroxylase (TyrH), a rate-limiting enzyme of catecholamine biosynthesis, was expressed and phosphorylated in adipose-resident macrophages. In addition, the plasma level of adrenaline was increased by cold stress in mice, and treatment of macrophages with adrenaline stimulated phosphorylation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and TyrH. Genetic and pharmacological inhibition of CaMKII or PKA signaling diminished adrenaline-induced phosphorylation of TyrH in primary macrophages. Consistently, overexpression of constitutively active CaMKII upregulated basal TyrH phosphorylation, while suppressing the stimulatory effect of adrenaline on TyrH in macrophages. Myeloid-specific disruption of CaMKIIγ suppressed both the cold-induced production of norepinephrine and adipose UCP1 expression in vivo and the stimulatory effect of adrenaline on macrophage-dependent activation of brown adipocytes in vitro. Lack of CaMKII signaling attenuated catecholamine production mediated by cytokines IL-4 and IL-13, key inducers of type 2 immune response in primary macrophages. Taken together, these results suggest a feedforward mechanism of adrenaline in adipose-resident macrophages, and that myeloid CaMKII signaling plays an important role in catecholamine production and subsequent beige fat activation. Oxford University Press 2017-10 2017-10-26 /pmc/articles/PMC5907839/ /pubmed/29087480 http://dx.doi.org/10.1093/jmcb/mjx046 Text en © The Author (2017). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.
institution US NLM
collection PubMed Central
language Inglês
format Artigo
topic Original Article
spellingShingle Original Article
Luo, Yan
Liu, Bilian
Yang, Xin
Ma, Xiaoxiao
Zhang, Xing
Bragin, Denis E
Yang, Xuexian O
Huang, Wendong
Liu, Meilian
Myeloid adrenergic signaling via CaMKII forms a feedforward loop of catecholamine biosynthesis
description Type 2 immune response has been shown to facilitate cold-induced thermogenesis and browning of white fat. However, whether alternatively activated macrophages produce catecholamine and substantially promote adaptive thermogenesis in adipose tissue remains controversial. Here, we show that tyrosine hydroxylase (TyrH), a rate-limiting enzyme of catecholamine biosynthesis, was expressed and phosphorylated in adipose-resident macrophages. In addition, the plasma level of adrenaline was increased by cold stress in mice, and treatment of macrophages with adrenaline stimulated phosphorylation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and TyrH. Genetic and pharmacological inhibition of CaMKII or PKA signaling diminished adrenaline-induced phosphorylation of TyrH in primary macrophages. Consistently, overexpression of constitutively active CaMKII upregulated basal TyrH phosphorylation, while suppressing the stimulatory effect of adrenaline on TyrH in macrophages. Myeloid-specific disruption of CaMKIIγ suppressed both the cold-induced production of norepinephrine and adipose UCP1 expression in vivo and the stimulatory effect of adrenaline on macrophage-dependent activation of brown adipocytes in vitro. Lack of CaMKII signaling attenuated catecholamine production mediated by cytokines IL-4 and IL-13, key inducers of type 2 immune response in primary macrophages. Taken together, these results suggest a feedforward mechanism of adrenaline in adipose-resident macrophages, and that myeloid CaMKII signaling plays an important role in catecholamine production and subsequent beige fat activation.
author Luo, Yan
Liu, Bilian
Yang, Xin
Ma, Xiaoxiao
Zhang, Xing
Bragin, Denis E
Yang, Xuexian O
Huang, Wendong
Liu, Meilian
author_facet Luo, Yan
Liu, Bilian
Yang, Xin
Ma, Xiaoxiao
Zhang, Xing
Bragin, Denis E
Yang, Xuexian O
Huang, Wendong
Liu, Meilian
author_sort Luo, Yan
title Myeloid adrenergic signaling via CaMKII forms a feedforward loop of catecholamine biosynthesis
title_short Myeloid adrenergic signaling via CaMKII forms a feedforward loop of catecholamine biosynthesis
title_full Myeloid adrenergic signaling via CaMKII forms a feedforward loop of catecholamine biosynthesis
title_fullStr Myeloid adrenergic signaling via CaMKII forms a feedforward loop of catecholamine biosynthesis
title_full_unstemmed Myeloid adrenergic signaling via CaMKII forms a feedforward loop of catecholamine biosynthesis
title_sort myeloid adrenergic signaling via camkii forms a feedforward loop of catecholamine biosynthesis
publisher Oxford University Press
container_title J Mol Cell Biol
publishDate 2017
url https://ncbi.nlm.nih.gov/pmc/articles/PMC5907839/
https://ncbi.nlm.nih.gov/pubmed/29087480
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1093/jmcb/mjx046
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