PUBLICATION
Leptin mutation and mycobacterial infection lead non-synergistically to a similar metabolic syndrome
- Authors
- Ding, Y., Haks, M.C., van den Eeden, S.J.F., Ottenhoff, T.H.M., Harms, A.C., Hankemeier, T., Eeza, M.N.H., Matysik, J., Alia, A., Spaink, H.P.
- ID
- ZDB-PUB-220808-2
- Date
- 2022
- Source
- Metabolomics : Official journal of the Metabolomic Society 18: 67 (Journal)
- Registered Authors
- Spaink, Herman P.
- Keywords
- Leptin mutant zebrafish, Metabolomics, Non-synergy, Ob/ob mice, Transcriptomics, Tuberculosis
- Datasets
- GEO:GSE211981
- MeSH Terms
-
- Animals
- Larva/genetics
- Larva/metabolism
- Leptin*/genetics
- Leptin*/metabolism
- Magnetic Resonance Spectroscopy
- Metabolomics
- Mice
- Mutation*
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 35933481 Full text @ Metabolomics
Citation
Ding, Y., Haks, M.C., van den Eeden, S.J.F., Ottenhoff, T.H.M., Harms, A.C., Hankemeier, T., Eeza, M.N.H., Matysik, J., Alia, A., Spaink, H.P. (2022) Leptin mutation and mycobacterial infection lead non-synergistically to a similar metabolic syndrome. Metabolomics : Official journal of the Metabolomic Society. 18:67.
Abstract
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 lepbibl54 mutant zebrafish larvae and wild type (WT) siblings after mycobacterial infection. These studies showed that mycobacteria induced a very distinct transcriptome signature in the lepbibl54 mutant zebrafish compared to WT sibling control larvae. Furthermore, lepbibl55 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 lepbibl54 mutant and TB can lead to the similar metabolic end states.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping