Hypothalamic CDK4 regulates thermogenesis by modulating sympathetic innervation of adipose tissues.
Judit Castillo-ArmengolValentin BarquissauSarah GellerHonglei JiIlenia SeveriWiebe VenemaEric Aria FenandezCatherine MoretKatharina HuberLucia C Leal-EstebanAnita NasrallahLaia Martinez-CarreresGuy NiederhäuserPatricia Seoane-CollazoSylviane LagarrigueMiguel LópezAntonio GiordanoSophie CroizierBernard ThorensIsabel C Lopez-MejiaLluis FajasPublished in: EMBO reports (2020)
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.
Keyphrases
- adipose tissue
- cell cycle
- high fat diet induced
- insulin resistance
- high fat diet
- cell proliferation
- gene expression
- poor prognosis
- oxidative stress
- stem cells
- metabolic syndrome
- bone marrow
- dna methylation
- genome wide
- single cell
- resting state
- long non coding rna
- brain injury
- blood brain barrier
- subarachnoid hemorrhage
- prefrontal cortex