Please use this identifier to cite or link to this item: https://repositorio.unifesp.br/handle/11600/38017
Title: Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy
Authors: Mori, Marcelo A. [UNIFESP]
Thomou, Thomas
Boucher, Jeremie
Lee, Kevin Y.
Lallukka, Susanna
Kim, Jason K.
Torriani, Martin
Yki-Jaervinen, Hannele
Grinspoon, Steven K.
Cypess, Aaron M.
Kahn, C. Ronald
Harvard Univ
Universidade Federal de São Paulo (UNIFESP)
AstraZeneca R&D
Univ Helsinki
Minerva Fdn
Univ Massachusetts
Massachusetts Gen Hosp
Issue Date: 1-Aug-2014
Publisher: Amer Soc Clinical Investigation Inc
Citation: Journal of Clinical Investigation. Ann Arbor: Amer Soc Clinical Investigation Inc, v. 124, n. 8, p. 3339-3351, 2014.
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.
URI: http://repositorio.unifesp.br/handle/11600/38017
ISSN: 0021-9738
Other Identifiers: http://dx.doi.org/10.1172/JCI73468
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