Dicer1-miR-328-Bace1 signalling controls brown adipose tissue differentiation and function

Dicer1-miR-328-Bace1 signalling controls brown adipose tissue differentiation and function

Author Oliverio, Matteo Google Scholar
Schmidt, Elena Google Scholar
Mauer, Jan Google Scholar
Baitzel, Catherina Google Scholar
Hansmeier, Nils Google Scholar
Khani, Sajjad Google Scholar
Konieczka, Sandra Google Scholar
Pradas-Juni, Marta Google Scholar
Brodesser, Susanne Google Scholar
Trieu-My Van Google Scholar
Bartsch, Deniz Google Scholar
Broenneke, Hella S. Google Scholar
Heine, Markus Google Scholar
Hilpert, Hans Google Scholar
Tarcitano, Emilio Autor UNIFESP Google Scholar
Garinis, George A. Google Scholar
Frommolt, Peter Google Scholar
Heeren, Joerg Google Scholar
Mori, Marcelo A. Autor UNIFESP Google Scholar
Bruening, Jens C. Google Scholar
Kornfeld, Jan-Wilhelm Google Scholar
Abstract Activation of brown adipose tissue (BAT) controls energy homeostasis in rodents and humans and has emerged as an innovative strategy for the treatment of obesity and type 2 diabetes mellitus(1-4). Here we show that ageing-and obesity-associated dysfunction of brown fat coincides with global microRNA downregulation due to reduced expression of the microRNA-processing node Dicer1. Consequently, heterozygosity of Dicer1 in BAT aggravated diet-induced-obesity (DIO)-evoked deterioration of glucose metabolism. Analyses of differential microRNA expression during preadipocyte commitment and mouse models of progeria, longevity and DIO identified miR-328 as a regulator of BAT differentiation. Reducing miR-328 blocked preadipocyte commitment, whereas miR-328 overexpression instigated BAT differentiation and impaired muscle progenitor commitment-partly through silencing of the beta-secretase Bace1. Loss of Bace1 enhanced brown preadipocyte specification in vitro and was overexpressed in BAT of obese and progeroid mice. In vivo Bace1 inhibition delayed DIO-induced weight gain and improved glucose tolerance and insulin sensitivity. These experiments reveal Dicer1-miR-328-Bace1 signalling as a determinant of BAT function, and highlight the potential of Bace1 inhibition as a therapeutic approach to improve not only neurodegenerative diseases but also ageing-and obesity-associated impairments of BAT function.
xmlui.dri2xhtml.METS-1.0.item-coverage London
Language English
Sponsor Emmy-Noether Program (DFG)
CECAD
Evangelisches Studienwerk Villigst
DAAD
CNPq
CAPES
FAPESP
Leibniz Preis
Cologne Center for Molecular Medicine Cologne (CMMC)
'Systems Biology of Ageing Cologne' (Sybacol).
Grant number Emmy-Noether Program (DFG): KO4728/1.1
FAPESP: 2010/52557-0
Leibniz Preis: BR1492/7-1
Date 2016
Published in Nature Cell Biology. London, v. 18, n. 3, p. 328-+, 2016.
ISSN 1465-7392 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent 328-+
Origin http://dx.doi.org/10.1038/ncb3316
Access rights Closed access
Type Article
Web of Science ID WOS:000371031300014
URI https://repositorio.unifesp.br/handle/11600/57923

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