Hypothalamic CDK4 regulates thermogenesis by modulating sympathetic innervation of adipose tissues.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_BA842E7BA291
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Hypothalamic CDK4 regulates thermogenesis by modulating sympathetic innervation of adipose tissues.
Journal
EMBO reports
Author(s)
Castillo-Armengol J., Barquissau V., Geller S., Ji H., Severi I., Venema W., Fenandez E.A., Moret C., Huber K., Leal-Esteban L.C., Nasrallah A., Martinez-Carreres L., Niederhäuser G., Seoane-Collazo P., Lagarrigue S., López M., Giordano A., Croizier S., Thorens B., Lopez-Mejia I.C., Fajas L.
ISSN
1469-3178 (Electronic)
ISSN-L
1469-221X
Publication state
Published
Issued date
03/09/2020
Peer-reviewed
Oui
Volume
21
Number
9
Pages
e49807
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
This study investigated the role of CDK4 in the oxidative metabolism of brown adipose tissue (BAT). BAT from Cdk4 <sup>-/-</sup> 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 <sup>-/-</sup> 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.
Keywords
CDK4, adrenergic innervation, brown adipose tissue, hypothalamus, mitochondria, thermogenesis
Pubmed
Web of science
Open Access
Yes
Create date
24/07/2020 10:53
Last modification date
14/10/2020 5:23
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