Hypothalamic CDK4 regulates thermogenesis by modulating sympathetic innervation of adipose tissues

Autor: Miguel López, Wiebe Venema, Lluis Fajas, Sylviane Lagarrigue, Sophie Croizier, Eric Aria Fenandez, Ilenia Severi, Honglei Ji, Patricia Seoane-Collazo, Lucia C Leal-Esteban, Judit Castillo-Armengol, Isabel C. Lopez-Mejia, Sarah Geller, Katharina Huber, Valentin Barquissau, Bernard Thorens, Guy Niederhauser, Antonio Giordano, Anita Nasrallah, Catherine Moret, Laia Martinez-Carreres
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: EMBO Reports
ISSN: 1469-3178
1469-221X
Popis: 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.
CDK4 negatively regulates thermogenesis by suppressing oxidative pathways. This study reveals that CDK4 also modulates the systemic regulation of metabolism through its action in the hypothalamus.
Databáze: OpenAIRE
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