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

Zebrafish*/genetics
Zebrafish*/metabolism
Larva/genetics
Larva/metabolism
Mice
Animals
Magnetic Resonance Spectroscopy
Metabolomics
Leptin*/genetics
Leptin*/metabolism
Mutation*

(all 11)

PubMed

35933481 Full text @ Metabolomics

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 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.

Genes / Markers

Figures

Show all Figures

Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	bacterial treatment by injection: Mycobacterium marinum M	Day 5	whole organism alanine decreased amount, abnormal	Fig. 2
WT	bacterial treatment by injection: Mycobacterium marinum M	Day 5	whole organism asparagine decreased amount, abnormal	Table 1
WT	bacterial treatment by injection: Mycobacterium marinum M	Day 5	whole organism aspartate decreased amount, abnormal	Fig. 2
WT	bacterial treatment by injection: Mycobacterium marinum M	Day 5	whole organism citrulline decreased amount, abnormal	Fig. 2
WT	bacterial treatment by injection: Mycobacterium marinum M	Day 5	whole organism cysteine decreased amount, abnormal	Table 1
WT	bacterial treatment by injection: Mycobacterium marinum M	Day 5	whole organism glycine decreased amount, abnormal	Table 1
WT	bacterial treatment by injection: Mycobacterium marinum M	Day 5	whole organism histidine decreased amount, abnormal	Table 1
WT	bacterial treatment by injection: Mycobacterium marinum M	Day 5	whole organism isoleucine decreased amount, abnormal	Table 1
WT	bacterial treatment by injection: Mycobacterium marinum M	Day 5	whole organism leucine decreased amount, abnormal	Table 1
WT	bacterial treatment by injection: Mycobacterium marinum M	Day 5	whole organism lysine decreased amount, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ibl54		Small Deletion	lepb
ibl55		Small Deletion	lepb
s952Tg	Tg(pck1:Luciferase,cryaa:mCherry)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
lepb^ibl54/ibl54
lepb^ibl55/ibl55; s952Tg
WT

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
Luciferase	EFG	Luciferase
mCherry	EFG	mCherry

Mapping

Ding et al., 2022 ZDB-PUB-220808-2 PMID:35933481

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

Ding et al., 2022

ZDB-PUB-220808-2
PMID:35933481