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Hypothalamic CDK4 regulates thermogenesis by modulating sympathetic innervation of adipose tissues.
Castillo-Armengol, Judit; Barquissau, Valentin; Geller, Sarah; Ji, Honglei; Severi, Ilenia; Venema, Wiebe; Fenandez, Eric Aria; Moret, Catherine; Huber, Katharina; Leal-Esteban, Lucia C; Nasrallah, Anita; Martinez-Carreres, Laia; Niederhäuser, Guy; Seoane-Collazo, Patricia; Lagarrigue, Sylviane; López, Miguel; Giordano, Antonio; Croizier, Sophie; Thorens, Bernard; Lopez-Mejia, Isabel C; Fajas, Lluis.
Afiliação
  • Castillo-Armengol J; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
  • Barquissau V; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
  • Geller S; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
  • Ji H; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
  • Severi I; Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy.
  • Venema W; Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy.
  • Fenandez EA; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
  • Moret C; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
  • Huber K; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
  • Leal-Esteban LC; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
  • Nasrallah A; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
  • Martinez-Carreres L; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
  • Niederhäuser G; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
  • Seoane-Collazo P; NeurObesity Group, Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.
  • Lagarrigue S; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, Spain.
  • López M; Department of Physiology, University of Lausanne, Lausanne, Switzerland.
  • Giordano A; NeurObesity Group, Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.
  • Croizier S; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, Spain.
  • Thorens B; Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy.
  • Lopez-Mejia IC; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
  • Fajas L; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
EMBO Rep ; 21(9): e49807, 2020 09 03.
Article em En | MEDLINE | ID: mdl-32657019
ABSTRACT
This study investigated the role of CDK4 in the oxidative metabolism of brown adipose tissue (BAT). BAT from Cdk4-/- mice exhibited fewer lipids and increased mitochondrial volume and expression of canonical thermogenic genes, rendering these mice more resistant to cold exposure. Interestingly, these effects were not BAT cell-autonomous but rather driven by increased sympathetic innervation. In particular, the ventromedial hypothalamus (VMH) is known to modulate BAT activation via the sympathetic nervous system. We thus examined the effects of VMH neuron-specific Cdk4 deletion. These mice display increased sympathetic innervation and enhanced cold tolerance, similar to Cdk4-/- mice, in addition to browning of scWAT. Overall, we provide evidence showing that CDK4 modulates thermogenesis by regulating sympathetic innervation of adipose tissue depots through hypothalamic nuclei, including the VMH. This demonstrates that CDK4 not only negatively regulates oxidative pathways, but also modulates the central regulation of metabolism through its action in the brain.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Termogênese / Tecido Adiposo Branco Limite: Animals Idioma: En Revista: EMBO Rep Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Suíça
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Termogênese / Tecido Adiposo Branco Limite: Animals Idioma: En Revista: EMBO Rep Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Suíça