SCD1 sustains brown fat sympathetic innervation and thermogenesis during the long-term cold exposure
SCD1 sustains brown fat sympathetic innervation and thermogenesis during the long-term cold exposure
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DOI：
10.1016/j.bbrc.2024.149493
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发表时间：
2024-01-13
影响因子：
3.1
通讯作者：
Luo，Wenjing
中科院分区：
文献类型：
--
作者：
Liu，Zongcai;Zhu，Sijin;Luo，Wenjing
棕色脂肪组织(BAT)是改善哺乳动物肥胖、糖尿病和冷适应的潜在治疗靶点。在长期的冷暴露过程中，交感神经网络的增生对蝙蝠维持高生热状态至关重要。已有研究证明，交感神经通过释放去甲肾上腺素来驱动蝙蝠的发热活动。然而，目前尚不清楚产热蝙蝠如何影响交感神经网络的重构，尤其是在长期寒冷环境中。在这里，我们发现，在长期的冷暴露后，SCD1介导的单不饱和脂肪酸生物合成途径在BAT中得到丰富，单不饱和/饱和脂肪酸的比例显著上调。BAT中SCD_1的缺失降低了BAT的冷驯化能力，并抑制了BAT长期的冷诱导产热激活。此外，通过热中频暴露和交感神经切除模型，我们揭示了BAT中SCD1缺乏影响发热活动，这种影响依赖于交感神经。在机制上，SCD_1缺乏导致棕榈酸(PA)/棕榈油酸(PO)比例失衡，导致PA水平明显升高，PO水平明显降低。补充PO可有效逆转SCD1缺乏对蝙蝠产热和交感神经网络增生的抑制作用。因此，我们的研究结果揭示了SCD1介导的单不饱和脂肪酸代谢在生热活性BAT和增生性交感神经网络相互作用中的作用，并阐明了单不饱和脂肪酸生物合成途径在长期冷暴露中冷适应中的关键作用。
Brown fat adipose tissue (BAT) is a therapeutic potential target to improve obesity, diabetes and cold acclimation in mammals. During the long-term cold exposure, the hyperplastic sympathetic network is crucial for BAT the maintain the highly thermogenic status. It has been proved that the sympathetic nervous drives the thermogenic activity of BAT via the release of norepinephrine. However, it is still unclear that how the thermogenic BAT affects the remodeling of the hyperplastic sympathetic network, especially during the long-term cold exposure. Here, we showed that following long-term cold exposure, SCD1-mediated monounsaturated fatty acid biosynthesis pathway was enriched, and the ratios of monounsaturated/saturated fatty acids were significantly up-regulated in BAT. And SCD1-deficiency in BAT decreased the capacity of cold acclimation, and suppressed long-term cold mediated BAT thermogenic activation. Furthermore, by using thermoneutral exposure and sympathetic nerve excision models, we disclosed that SCD1-deficiency in BAT affected the thermogenic activity, depended on sympathetic nerve. In mechanism, SCD1-deficiency resulted in the unbalanced ratio of palmitic acid (PA)/palmitoleic acid (PO), with obviously higher level of PA and lower level of PO. And PO supplement efficiently reversed the inhibitory role of SCD1-deficiency on BAT thermogenesis and the hyperplastic sympathetic network. Thus, our data provided insight into the role of SCD1-mediated monounsaturated fatty acids metabolism to the interaction between thermogenic activity BAT and hyperplastic sympathetic networks, and illustrated the critical role of monounsaturated fatty acids biosynthetic pathway in cold acclimation during the long-term cold exposure.