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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| Veröffentlicht in: | Nutrients 2021-10, Vol.13 (11), p.3735 |
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| creator | Breuer, Saida Kasper, Philipp Vohlen, Christina Janoschek, Ruth Hoffmann, Thorben Appel, Sarah Müller-Limberger, Elena Mesaros, Andrea Rose-John, Stefan Garbers, Christoph Müller, Stefan Lackmann, Jan-Wilm Mahabir, Esther Dötsch, Jörg Hucklenbruch-Rother, Eva Bae-Gartz, Inga |
| 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 (
) 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
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. |
| doi_str_mv | 10.3390/nu13113735 |
| format | Article |
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) 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
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.</description><identifier>ISSN: 2072-6643</identifier><identifier>EISSN: 2072-6643</identifier><identifier>DOI: 10.3390/nu13113735</identifier><identifier>PMID: 34835991</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adipokines - genetics ; Adipokines - metabolism ; Adipose tissue ; Adipose Tissue, White - metabolism ; Animal welfare ; Animals ; Biomarkers - blood ; Body composition ; Body fat ; Body Weight ; Brain ; Brain - metabolism ; Breastfeeding & lactation ; Cytokines ; Diet ; Diet, Western ; Female ; Glucose tolerance ; Glucose Tolerance Test ; Glycoprotein gp130 ; Glycoproteins ; Homeostasis ; Human nutrition ; Hypothalamus ; Inflammation ; Insulin - metabolism ; Interleukin 6 ; Interleukin-6 - metabolism ; Laboratory animals ; Lactation ; Male ; Metabolism ; Mice ; Mice, Inbred C57BL ; Nervous system ; Neurogenesis ; Nutrition ; Nutrition research ; Obesity ; Obesity, Maternal - blood ; Obesity, Maternal - metabolism ; Offspring ; Phenotype ; Pregnancy ; Proteins ; Proteome - metabolism ; Proteomes ; Proteomics ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Signal Transduction ; Transgenic animals ; Transgenic mice</subject><ispartof>Nutrients, 2021-10, Vol.13 (11), p.3735</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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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 (
) 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
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. 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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 (
) 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
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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>34835991</pmid><doi>10.3390/nu13113735</doi><orcidid>https://orcid.org/0000-0002-7519-3279</orcidid><orcidid>https://orcid.org/0000-0003-4939-6950</orcidid><orcidid>https://orcid.org/0000-0003-3723-5762</orcidid><orcidid>https://orcid.org/0000-0002-6218-2239</orcidid><orcidid>https://orcid.org/0000-0003-0315-6513</orcidid><orcidid>https://orcid.org/0000-0002-9573-5127</orcidid><orcidid>https://orcid.org/0000-0001-8182-8034</orcidid><orcidid>https://orcid.org/0000-0002-4061-503X</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 2072-6643 |
| ispartof | Nutrients, 2021-10, Vol.13 (11), p.3735 |
| issn | 2072-6643 2072-6643 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8618896 |
| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Adipokines - genetics Adipokines - metabolism Adipose tissue Adipose Tissue, White - metabolism Animal welfare Animals Biomarkers - blood Body composition Body fat Body Weight Brain Brain - metabolism Breastfeeding & lactation Cytokines Diet Diet, Western Female Glucose tolerance Glucose Tolerance Test Glycoprotein gp130 Glycoproteins Homeostasis Human nutrition Hypothalamus Inflammation Insulin - metabolism Interleukin 6 Interleukin-6 - metabolism Laboratory animals Lactation Male Metabolism Mice Mice, Inbred C57BL Nervous system Neurogenesis Nutrition Nutrition research Obesity Obesity, Maternal - blood Obesity, Maternal - metabolism Offspring Phenotype Pregnancy Proteins Proteome - metabolism Proteomes Proteomics RNA, Messenger - genetics RNA, Messenger - metabolism Signal Transduction Transgenic animals Transgenic mice |
| title | Brain-Restricted Inhibition of IL-6 Trans-Signaling Mildly Affects Metabolic Consequences of Maternal Obesity in Male Offspring |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T01%3A32%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Brain-Restricted%20Inhibition%20of%20IL-6%20Trans-Signaling%20Mildly%20Affects%20Metabolic%20Consequences%20of%20Maternal%20Obesity%20in%20Male%20Offspring&rft.jtitle=Nutrients&rft.au=Breuer,%20Saida&rft.date=2021-10-23&rft.volume=13&rft.issue=11&rft.spage=3735&rft.pages=3735-&rft.issn=2072-6643&rft.eissn=2072-6643&rft_id=info:doi/10.3390/nu13113735&rft_dat=%3Cproquest_pubme%3E2604025534%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2602162324&rft_id=info:pmid/34835991&rfr_iscdi=true |