Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy

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dc.contributor.author Mori, Marcelo A. [UNIFESP]
dc.contributor.author Thomou, Thomas
dc.contributor.author Boucher, Jeremie
dc.contributor.author Lee, Kevin Y.
dc.contributor.author Lallukka, Susanna
dc.contributor.author Kim, Jason K.
dc.contributor.author Torriani, Martin
dc.contributor.author Yki-Jaervinen, Hannele
dc.contributor.author Grinspoon, Steven K.
dc.contributor.author Cypess, Aaron M.
dc.contributor.author Kahn, C. Ronald
dc.date.accessioned 2016-01-24T14:37:37Z
dc.date.available 2016-01-24T14:37:37Z
dc.date.issued 2014-08-01
dc.identifier http://dx.doi.org/10.1172/JCI73468
dc.identifier.citation Journal of Clinical Investigation. Ann Arbor: Amer Soc Clinical Investigation Inc, v. 124, n. 8, p. 3339-3351, 2014.
dc.identifier.issn 0021-9738
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/38017
dc.description.abstract miRNAs are important regulators of biological processes in many tissues, including the differentiation and function of brown and white adipocytes. the endoribonuclease dicer is a major component of the miRNA-processing pathway, and in adipose tissue, levels of dicer have been shown to decrease with age, increase with caloric restriction, and influence stress resistance. Here, we demonstrated that mice with a fat-specific KO of dicer develop a form of lipodystrophy that is characterized by loss of intra-abdominal and subcutaneous white fat, severe insulin resistance, and enlargement and whitening of interscapular brown fat. Additionally, KO of dicer in cultured brown preadipocytes promoted a white adipocyte-like phenotype and reduced expression of several miRNAs. Brown preadipocyte whitening was partially reversed by expression of miR-365, a miRNA known to promote brown fat differentiation; however, introduction of other miRNAs, including miR-346 and miR-362, also contributed to reversal of the loss of the dicer phenotype. Interestingly, fat samples from patients with HIV-related lipodystrophy exhibited a substantial downregulation of dicer mRNA expression. Together, these findings indicate the importance of miRNA processing in white and brown adipose tissue determination and provide a potential link between this process and HIV-related lipodystrophy. en
dc.description.sponsorship NIH
dc.description.sponsorship Ellison Foundation
dc.description.sponsorship Joslin Diabetes and Endocrinology Research Center cores
dc.description.sponsorship Mary K. Iacocca Professorship
dc.description.sponsorship Academy of Finland
dc.description.sponsorship Sigrid Juselius Foundation
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.format.extent 3339-3351
dc.language.iso eng
dc.publisher Amer Soc Clinical Investigation Inc
dc.relation.ispartof Journal of Clinical Investigation
dc.rights Acesso aberto
dc.title Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy en
dc.type Artigo
dc.contributor.institution Harvard Univ
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution AstraZeneca R&D
dc.contributor.institution Univ Helsinki
dc.contributor.institution Minerva Fdn
dc.contributor.institution Univ Massachusetts
dc.contributor.institution Massachusetts Gen Hosp
dc.description.affiliation Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA
dc.description.affiliation Universidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Program Mol Biol, São Paulo, Brazil
dc.description.affiliation AstraZeneca R&D, Cardiovasc & Metab Dis iMed, Molndal, Sweden
dc.description.affiliation Univ Helsinki, Dept Med, Helsinki, Finland
dc.description.affiliation Minerva Fdn, Inst Med Res, Helsinki, Finland
dc.description.affiliation Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA USA
dc.description.affiliation Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA
dc.description.affiliation Harvard Univ, Sch Med, Boston, MA USA
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Program Mol Biol, São Paulo, Brazil
dc.description.sponsorshipID NIH: DK082659
dc.description.sponsorshipID NIH: DK033201
dc.description.sponsorshipID NIH: AI060354
dc.description.sponsorshipID NIH: DK040561
dc.description.sponsorshipID NIH: U24-DK093000
dc.description.sponsorshipID Joslin Diabetes and Endocrinology Research Center cores: DK036836
dc.description.sponsorshipID FAPESP: 2010/52557-0
dc.identifier.file WOS000339984000011.pdf
dc.identifier.doi 10.1172/JCI73468
dc.description.source Web of Science
dc.identifier.wos WOS:000339984000011



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