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

Publisher: Springer Country of Publication: United States NLM ID: 101274889 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-3890 (Electronic) Linking ISSN: 15733882 NLM ISO Abbreviation: Metabolomics Subsets: MEDLINE

Original Publication: New York : Springer, c2006-

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

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.
(© 2022. The Author(s).)

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Keywords: Leptin mutant zebrafish; Metabolomics; Non-synergy; Ob/ob mice; Transcriptomics; Tuberculosis

0 (Leptin)

Date Created: 20220806 Date Completed: 20220809 Latest Revision: 20251031

20260130

PMC9356939

10.1007/s11306-022-01921-8

35933481