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.

Hypothalamic CDK4 regulates thermogenesis by modulating sympathetic innervation of adipose tissues / 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.; Niederhauser, G.; Seoane-Collazo, P.; Lagarrigue, S.; Lopez, M.; Giordano, A.; Croizier, S.; Thorens, B.; Lopez-Mejia, I. C.; Fajas, L.. - In: EMBO REPORTS. - ISSN 1469-221X. - ELETTRONICO. - 21:9(2020), p. e49807. [10.15252/embr.201949807]

Hypothalamic CDK4 regulates thermogenesis by modulating sympathetic innervation of adipose tissues

Severi I.
Membro del Collaboration Group
;
Venema W.
Membro del Collaboration Group
;
Giordano A.
Membro del Collaboration Group
;
2020-01-01

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.
2020
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/283895
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 10
social impact