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

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

Author Mori, Marcelo A. Autor UNIFESP Google Scholar
Thomou, Thomas Google Scholar
Boucher, Jeremie Google Scholar
Lee, Kevin Y. Google Scholar
Lallukka, Susanna Google Scholar
Kim, Jason K. Google Scholar
Torriani, Martin Google Scholar
Yki-Jaervinen, Hannele Google Scholar
Grinspoon, Steven K. Google Scholar
Cypess, Aaron M. Google Scholar
Kahn, C. Ronald Google Scholar
Institution Harvard Univ
Universidade Federal de São Paulo (UNIFESP)
AstraZeneca R&D
Univ Helsinki
Minerva Fdn
Univ Massachusetts
Massachusetts Gen Hosp
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.
Language English
Sponsor NIH
Ellison Foundation
Joslin Diabetes and Endocrinology Research Center cores
Mary K. Iacocca Professorship
Academy of Finland
Sigrid Juselius Foundation
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number NIH: DK082659
NIH: DK033201
NIH: AI060354
NIH: DK040561
NIH: U24-DK093000
Joslin Diabetes and Endocrinology Research Center cores: DK036836
FAPESP: 2010/52557-0
Date 2014-08-01
Published in Journal of Clinical Investigation. Ann Arbor: Amer Soc Clinical Investigation Inc, v. 124, n. 8, p. 3339-3351, 2014.
ISSN 0021-9738 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Clinical Investigation Inc
Extent 3339-3351
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000339984000011

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