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

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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	perinatal programming maternal nutrition newborn nutrition IL-6-trans-signaling hypothalamic dysfunction prevention Nutrition. Foods and food supply TX341-641
Acceso en línea:	https://doaj.org/article/7679340d997c4ce0b91e13159dad4118
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spelling	oai:doaj.org-article:7679340d997c4ce0b91e13159dad41182021-11-25T18:33:36ZBrain-Restricted Inhibition of IL-6 Trans-Signaling Mildly Affects Metabolic Consequences of Maternal Obesity in Male Offspring10.3390/nu131137352072-6643https://doaj.org/article/7679340d997c4ce0b91e13159dad41182021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6643/13/11/3735https://doaj.org/toc/2072-6643Maternal 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 (<sup>GFAPsgp130</sup>) 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 <sup>GFAPsgp130</sup>WSD 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.Saida BreuerPhilipp KasperChristina VohlenRuth JanoschekThorben HoffmannSarah AppelElena Müller-LimbergerAndrea MesarosStefan Rose-JohnChristoph GarbersStefan MüllerJan-Wilm LackmannEsther MahabirJörg DötschEva Hucklenbruch-RotherInga Bae-GartzMDPI AGarticleperinatal programmingmaternal nutritionnewborn nutritionIL-6-trans-signalinghypothalamic dysfunctionpreventionNutrition. Foods and food supplyTX341-641ENNutrients, Vol 13, Iss 3735, p 3735 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	perinatal programming maternal nutrition newborn nutrition IL-6-trans-signaling hypothalamic dysfunction prevention Nutrition. Foods and food supply TX341-641
spellingShingle	perinatal programming maternal nutrition newborn nutrition IL-6-trans-signaling hypothalamic dysfunction prevention Nutrition. Foods and food supply TX341-641 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 Brain-Restricted Inhibition of IL-6 Trans-Signaling Mildly Affects Metabolic Consequences of Maternal Obesity in Male Offspring
description	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 (<sup>GFAPsgp130</sup>) 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 <sup>GFAPsgp130</sup>WSD 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.
format	article
author	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
author_facet	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
author_sort	Saida Breuer
title	Brain-Restricted Inhibition of IL-6 Trans-Signaling Mildly Affects Metabolic Consequences of Maternal Obesity in Male Offspring
title_short	Brain-Restricted Inhibition of IL-6 Trans-Signaling Mildly Affects Metabolic Consequences of Maternal Obesity in Male Offspring
title_full	Brain-Restricted Inhibition of IL-6 Trans-Signaling Mildly Affects Metabolic Consequences of Maternal Obesity in Male Offspring
title_fullStr	Brain-Restricted Inhibition of IL-6 Trans-Signaling Mildly Affects Metabolic Consequences of Maternal Obesity in Male Offspring
title_full_unstemmed	Brain-Restricted Inhibition of IL-6 Trans-Signaling Mildly Affects Metabolic Consequences of Maternal Obesity in Male Offspring
title_sort	brain-restricted inhibition of il-6 trans-signaling mildly affects metabolic consequences of maternal obesity in male offspring
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7679340d997c4ce0b91e13159dad4118
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Brain-Restricted Inhibition of IL-6 Trans-Signaling Mildly Affects Metabolic Consequences of Maternal Obesity in Male Offspring

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