Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands.
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Metabolomics. 2022 Aug 7;18(8):67. doi: 10.1007/s11306-022-01921-8.
The leptin signaling pathway plays an important role as a key regulator of glucose homeostasis, metabolism control and systemic inflammatory responses. However, the metabolic effects of leptin on infectious diseases, for example tuberculosis (TB), are still little known.
In this study, we aim to investigate the role of leptin on metabolism in the absence and presence of mycobacterial infection in zebrafish larvae and mice.
Metabolites in entire zebrafish larvae and the blood of mice were studied using high-resolution magic-angle-spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy and mass spectrometry, respectively. For transcriptome studies of zebrafish larvae, deep RNA sequencing was used.
The results show that leptin mutation leads to a similar metabolic syndrome as caused by mycobacterial infection in the two species, characterized by the decrease of 11 amine metabolites. In both species, this metabolic syndrome was not aggravated further when the leptin mutant was infected by mycobacteria. Therefore, we conclude that leptin and mycobacterial infection are both impacting metabolism non-synergistically. In addition, we studied the transcriptomes of lepb mutant zebrafish larvae and wild type (WT) siblings after mycobacterial infection. These studies showed that mycobacteria induced a very distinct transcriptome signature in the lepb mutant zebrafish compared to WT sibling control larvae. Furthermore, lepb Tg (pck1:luc1) zebrafish line was constructed and confirmed this difference in transcriptional responses.
Leptin mutation and TB lead non-synergistically to a similar metabolic syndrome. Moreover, different transcriptomic responses in the lepb mutant and TB can lead to the similar metabolic end states.
瘦素信号通路作为葡萄糖稳态、代谢控制和全身炎症反应的关键调节剂，起着重要作用。然而，瘦素对传染病（例如结核病，TB）的代谢作用仍知之甚少。
在本研究中，我们旨在研究瘦素在斑马鱼幼虫和小鼠中缺乏和存在分枝杆菌感染时对代谢的作用。
使用高分辨率魔角旋转核磁共振（HR-MAS NMR）光谱和质谱法分别研究整个斑马鱼幼虫和小鼠血液中的代谢物。对于斑马鱼幼虫的转录组研究，使用深度 RNA 测序。
结果表明，瘦素突变导致两种物种中类似分枝杆菌感染引起的代谢综合征，其特征是 11 种胺代谢物减少。在这两个物种中，当瘦素突变体被分枝杆菌感染时，这种代谢综合征并没有进一步加重。因此，我们得出结论，瘦素和分枝杆菌感染对代谢的影响是非协同的。此外，我们研究了感染分枝杆菌后瘦素突变斑马鱼幼虫和野生型（WT）同窝仔鱼的转录组。这些研究表明，与 WT 同窝仔鱼对照幼虫相比，分枝杆菌在瘦素突变斑马鱼幼虫中诱导了非常独特的转录组特征。此外，构建了 lepB Tg（pck1:luc1）斑马鱼系，并证实了这种转录反应的差异。
瘦素突变和结核病非协同地导致类似的代谢综合征。此外，lepB 突变和结核病在不同的转录组反应中可能导致类似的代谢终末状态。
