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|Title:||Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy|
|Authors:||Mori, Marcelo A. [UNIFESP]|
Lee, Kevin Y.
Kim, Jason K.
Grinspoon, Steven K.
Cypess, Aaron M.
Kahn, C. Ronald
Universidade Federal de São Paulo (UNIFESP)
Massachusetts Gen Hosp
|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.|
|Appears in Collections:||Em verificação - Geral|
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