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.

中文翻译：

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下丘脑CDK4通过调节脂肪组织的交感神经来调节生热作用。

这项研究调查了CDK4在棕色脂肪组织（BAT）氧化代谢中的作用。来自Cdk4 ^-//小鼠的BAT表现出更少的脂质和增加的线粒体体积以及经典的热基因表达，使这些小鼠对冷暴露更具抵抗力。有趣的是，这些效应不是BAT细胞自主的，而是由交感神经支配的增加所驱动。特别是，已知腹侧下丘脑（VMH）通过交感神经系统调节BAT活化。因此，我们检查了VMH神经元特异性Cdk4缺失的影响。这些小鼠表现出增加的交感神经支配能力和增强的耐寒性，类似于Cdk4 ^-/-小鼠，除了scWAT褐变。总的来说，我们提供的证据表明CDK4通过调节下丘脑核（包括VMH）的脂肪组织组织的交感神经调节来调节生热。这表明CDK4不仅负调节氧化途径，而且还通过其在大脑中的作用调节新陈代谢的中央调节。