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Leptin mutation and mycobacterial infection lead non-synergistically to a similar metabolic syndrome.
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.
Afiliación
  • Ding Y; Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands.
  • Haks MC; Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
  • van den Eeden SJF; Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
  • Ottenhoff THM; Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
  • Harms AC; Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
  • Hankemeier T; Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
  • Eeza MNH; Institute of Analytical Chemistry, University of Leipzig, Leipzig, Germany.
  • Matysik J; Institute for Medical Physics and Biophysics, University of Leipzig, Leipzig, Germany.
  • Alia A; Institute of Analytical Chemistry, University of Leipzig, Leipzig, Germany.
  • Spaink HP; Institute for Medical Physics and Biophysics, University of Leipzig, Leipzig, Germany.
Metabolomics ; 18(8): 67, 2022 08 07.
Article en En | MEDLINE | ID: mdl-35933481
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Leptina / Mutación Límite: Animals Idioma: En Revista: Metabolomics Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Leptina / Mutación Límite: Animals Idioma: En Revista: Metabolomics Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos