Brain-Restricted Inhibition of IL-6 Trans-Signaling Mildly Affects Metabolic Consequences of Maternal Obesity in Male Offspring

Saida Breuer; Philipp Kasper; Christina Vohlen; Ruth Janoschek; Thorben Hoffmann; Sarah Appel; Elena Müller-Limberger; Andrea Mesaros; Stefan Rose-John; Christoph Garbers; Stefan Müller; Jan-Wilm Lackmann; Esther Mahabir; Jörg Dötsch; Eva Hucklenbruch-Rother; Inga Bae-Gartz

doi:10.3390/nu13113735

Nutrients (Oct 2021)

Brain-Restricted Inhibition of IL-6 Trans-Signaling Mildly Affects Metabolic Consequences of Maternal Obesity in Male Offspring

Saida Breuer,
Philipp Kasper,
Christina Vohlen,
Ruth Janoschek,
Thorben Hoffmann,
Sarah Appel,
Elena Müller-Limberger,
Andrea Mesaros,
Stefan Rose-John,
Christoph Garbers,
Stefan Müller,
Jan-Wilm Lackmann,
Esther Mahabir,
Jörg Dötsch,
Eva Hucklenbruch-Rother,
Inga Bae-Gartz

Affiliations

Saida Breuer: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Philipp Kasper: Clinic for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Christina Vohlen: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Ruth Janoschek: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Thorben Hoffmann: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Sarah Appel: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Elena Müller-Limberger: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Andrea Mesaros: Department of Phenotyping, Max-Planck Institute for Biology of Aging, University of Cologne, D-50931 Cologne, Germany
Stefan Rose-John: Department for Biochemistry, Christian-Albrechts-University zu Kiel, D-24098 Kiel, Germany
Christoph Garbers: Department of Pathology, Medical Faculty, Otto-von-Guericke-University Magdeburg, D-39120 Magdeburg, Germany
Stefan Müller: Center for Molecular Medicine (CMMC), Proteomics Facility, University of Cologne, D-50931 Cologne, Germany
Jan-Wilm Lackmann: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, D-50931 Cologne, Germany
Esther Mahabir: Comparative Medicine, Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, D-50937 Cologne, Germany
Jörg Dötsch: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Eva Hucklenbruch-Rother: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany
Inga Bae-Gartz: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany

DOI: https://doi.org/10.3390/nu13113735
Journal volume & issue: Vol. 13, no. 11
p. 3735

Abstract

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Maternal obesity greatly affects next generations, elevating obesity risk in the offspring through perinatal programming and flawed maternal and newborn nutrition. The exact underlying mechanisms are poorly understood. Interleukin-6 (IL-6) mediates its effects through a membrane-bound receptor or by trans-signaling (tS), which can be inhibited by the soluble form of the co-receptor gp130 (sgp130). As IL-6 tS mediates western-style diet (WSD) effects via chronic low-grade inflammation (LGI) and LGI is an important mediator in brain–adipose tissue communication, this study aims at determining the effects of maternal obesity in a transgenic mouse model of brain-restricted IL-6tS inhibition (GFAPsgp130) on offspring’s short- and long-term body composition and epigonadal white adipose tissue (egWAT) metabolism. Female wild type (WT) or transgenic mice were fed either standard diet (SD) or WSD pregestationally, during gestation, and lactation. Male offspring received SD from postnatal day (P)21 to P56 and were metabolically challenged with WSD from P56 to P120. At P21, offspring from WT and transgenic dams that were fed WSD displayed increased body weight and egWAT mass, while glucose tolerance testing showed the strongest impairment in GFAPsgp130WSD offspring. Simultaneously, egWAT proteome reveals a characteristic egWAT expression pattern in offspring as a result of maternal conditions. IL-6tS inhibition in transgenic mice was in tendency associated with lower body weight in dams on SD and their respective offspring but blunted by the WSD. In conclusion, maternal nutrition affects offspring’s body weight and egWAT metabolism predominantly independent of IL-6tS inhibition, emphasizing the importance of maternal and newborn nutrition for long-term offspring health.

Published in Nutrients

ISSN: 2072-6643 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Technology: Home economics: Nutrition. Foods and food supply
Website: https://www.mdpi.com/journal/nutrients

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