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Dicer1-miR-328-Bace1 signalling controls brown adipose tissue differentiation and function.
Oliverio, Matteo; Schmidt, Elena; Mauer, Jan; Baitzel, Catherina; Hansmeier, Nils; Khani, Sajjad; Konieczka, Sandra; Pradas-Juni, Marta; Brodesser, Susanne; Van, Trieu-My; Bartsch, Deniz; Brönneke, Hella S; Heine, Markus; Hilpert, Hans; Tarcitano, Emilio; Garinis, George A; Frommolt, Peter; Heeren, Joerg; Mori, Marcelo A; Brüning, Jens C; Kornfeld, Jan-Wilhelm.
Afiliación
  • Oliverio M; Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
  • Schmidt E; Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD), D-50931 Cologne, Germany.
  • Mauer J; Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
  • Baitzel C; Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD), D-50931 Cologne, Germany.
  • Hansmeier N; Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
  • Khani S; Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD), D-50931 Cologne, Germany.
  • Konieczka S; Department of Pharmacology, Weill Medical College, Cornell University, New York 10035, USA.
  • Pradas-Juni M; Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
  • Brodesser S; Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD), D-50931 Cologne, Germany.
  • Van TM; Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
  • Bartsch D; Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD), D-50931 Cologne, Germany.
  • Brönneke HS; Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
  • Heine M; Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD), D-50931 Cologne, Germany.
  • Hilpert H; Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
  • Tarcitano E; Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD), D-50931 Cologne, Germany.
  • Garinis GA; Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
  • Frommolt P; Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD), D-50931 Cologne, Germany.
  • Heeren J; Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD), D-50931 Cologne, Germany.
  • Mori MA; Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD), D-50931 Cologne, Germany.
  • Brüning JC; Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
  • Kornfeld JW; Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD), D-50931 Cologne, Germany.
Nat Cell Biol ; 18(3): 328-36, 2016 Mar.
Article en En | MEDLINE | ID: mdl-26900752
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. 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 ß-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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tejido Adiposo Pardo / Diferenciación Celular / Ácido Aspártico Endopeptidasas / MicroARNs / Ribonucleasa III / Secretasas de la Proteína Precursora del Amiloide / ARN Helicasas DEAD-box Límite: Animals Idioma: En Revista: Nat Cell Biol Año: 2016 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tejido Adiposo Pardo / Diferenciación Celular / Ácido Aspártico Endopeptidasas / MicroARNs / Ribonucleasa III / Secretasas de la Proteína Precursora del Amiloide / ARN Helicasas DEAD-box Límite: Animals Idioma: En Revista: Nat Cell Biol Año: 2016 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido