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

• Published in: Metabolomics Vol. 18; no. 8; p. 67
• Main Authors: Ding, Yi, Haks, Mariëlle C., van den Eeden, Susan J. F., Ottenhoff, Tom H. M., Harms, Amy C., Hankemeier, Thomas, Eeza, Muhamed N. H., Matysik, Jörg, Alia, A., Spaink, Herman P.
• Format: Journal Article
• Language: English
• Published: New York Springer US 07-08-2022; Springer Nature B.V
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Danio rerio; Developmental Biology; Glucose metabolism; Homeostasis; Infections; Infectious diseases; Inflammation; Larvae; Leptin; Life Sciences; Mass spectroscopy; Metabolic syndrome; Metabolites; Molecular Medicine; Mutants; Mutation; NMR; Nuclear magnetic resonance; Original; Original Article; Signal transduction; Transcriptomes; Transcriptomics; Tuberculosis; Non-synergy; Metabolomics; Tuberculosis; Leptin mutant zebrafish; Transcriptomics; mice
• ISSN: 1573-3890; 1573-3882; 1573-3890
• DOI: 10.1007/s11306-022-01921-8

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.