Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue

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dc.contributor.authorSouza S.C.
dc.contributor.authorChristoffolete M.A.
dc.contributor.authorRibeiro M.O.
dc.contributor.authorMiyoshi H.
dc.contributor.authorStrissel K.J.
dc.contributor.authorStancheva Z.S.
dc.contributor.authorRogers N.H.
dc.contributor.authorD'Eon T.M.
dc.contributor.authorPerfield II J.W.
dc.contributor.authorImachi H.
dc.contributor.authorObin M.S.
dc.contributor.authorBianco A.C.
dc.contributor.authorGreenberg A.S.
dc.date.accessioned2024-03-13T01:39:52Z
dc.date.available2024-03-13T01:39:52Z
dc.date.issued2007
dc.description.abstractIn response to cold, norepinephrine (NE)-induced triacylglycerol hydrolysis (lipolysis) in adipocytes of brown adipose tissue (BAT) provides fatty acid substrates to mitochondria for heat generation (adaptive thermogenesis). NE-induced lipolysis is mediated by protein kinase A (PKA)-dependent phosphorylation of perilipin, a lipid droplet-associated protein that is the major regulator of lipolysis. We investigated the role of perilipin PKA phosphorylation in BAT NE-stimulated thermogenesis using a novel mouse model in which a mutant form of perilipin, lacking all six PKA phosphorylation sites, is expressed in adipocytes of perilipin knockout (Peri KO) mice. Here, we show that despite a normal mitochondrial respiratory capacity, NE-induced lipolysis is abrogated in the interscapular brown adipose tissue (IBAT) of these mice. This lipolytic constraint is accompanied by a dramatic blunting (∼70%) of the in vivo thermal response to NE. Thus, in the presence of perilipin, PKA-mediated perilipin phosphorylation is essential for NE-dependent lipolysis and full adaptive thermogenesis in BAT. In IBAT of Peri KO mice, increased basal lipolysis attributable to the absence of perilipin is sufficient to support a rapid NE-stimulated temperature increase (∼3.0°C) comparable to that in wild-type mice. This observation suggests that one or more NE-dependent mechanism downstream of perilipin phosphorylation is required to initiate and/or sustain the IBAT thermal response.
dc.description.firstpage1273
dc.description.issuenumber6
dc.description.lastpage1279
dc.description.volume48
dc.identifier.doi10.1194/jlr.M700047-JLR200
dc.identifier.issn0022-2275
dc.identifier.urihttps://dspace.mackenzie.br/handle/10899/37648
dc.relation.ispartofJournal of Lipid Research
dc.rightsAcesso Aberto
dc.subject.otherlanguageBrown adipocytes
dc.subject.otherlanguageNorepinephrine-induced thermal response
dc.subject.otherlanguageProtein kinase A-stimulated lipolysis
dc.titlePerilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue
dc.typeArtigo
local.scopus.citations39
local.scopus.eid2-s2.0-34548160963
local.scopus.updated2024-05-01
local.scopus.urlhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=34548160963&origin=inward
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