Leptin mutation and mycobacterial infection lead non-synergistically to a similar metabolic syndrome

Introduction 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. Objectives 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. Methods 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. Results 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(ibl54) 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(ibl54) mutant zebrafish compared to WT sibling control larvae. Furthermore, lepb(ibl55) Tg (pck1:luc1) zebrafish line was constructed and confirmed this difference in transcriptional responses. Conclusions Leptin mutation and TB lead non-synergistically to a similar metabolic syndrome. Moreover, different transcriptomic responses in the lepb(ibl54) mutant and TB can lead to the similar metabolic end states.

Automated summary

The leptin signaling pathway plays an important role in regulating glucose homeostasis, metabolism, and systemic inflammatory responses. However, its metabolic effects on infectious diseases like tuberculosis are not well understood. In this study, the researchers investigated the role of leptin in metabolism in zebrafish larvae and mice in the absence and presence of mycobacterial infection. They found that leptin mutation and mycobacterial infection lead to a similar metabolic syndrome characterized by a decrease in 11 amine metabolites. The researchers concluded that leptin and mycobacterial infection impact metabolism independently, without a synergistic effect. They also observed distinct transcriptomic responses in the leptin mutant zebrafish larvae and mycobacterial infection, which can lead to similar metabolic end states.