PMID- 34835991
OWN - NLM
STAT- MEDLINE
DCOM- 20211209
LR  - 20240226
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 13
IP  - 11
DP  - 2021 Oct 23
TI  - Brain-Restricted Inhibition of IL-6 Trans-Signaling Mildly Affects Metabolic 
      Consequences of Maternal Obesity in Male Offspring.
LID - 10.3390/nu13113735 [doi]
LID - 3735
AB  - 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 (GFAPsgp130)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.
FAU - Breuer, Saida
AU  - Breuer S
AUID- ORCID: 0000-0003-3723-5762
AD  - Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and 
      University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany.
FAU - Kasper, Philipp
AU  - Kasper P
AUID- ORCID: 0000-0002-6218-2239
AD  - Clinic for Gastroenterology and Hepatology, Faculty of Medicine and University 
      Hospital Cologne, University of Cologne, D-50937 Cologne, Germany.
FAU - Vohlen, Christina
AU  - Vohlen C
AD  - Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and 
      University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany.
FAU - Janoschek, Ruth
AU  - Janoschek R
AD  - Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and 
      University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany.
FAU - Hoffmann, Thorben
AU  - Hoffmann T
AD  - Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and 
      University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany.
FAU - Appel, Sarah
AU  - Appel S
AUID- ORCID: 0000-0003-0315-6513
AD  - Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and 
      University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany.
FAU - Muller-Limberger, Elena
AU  - Muller-Limberger E
AD  - Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and 
      University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany.
FAU - Mesaros, Andrea
AU  - Mesaros A
AD  - Department of Phenotyping, Max-Planck Institute for Biology of Aging, University 
      of Cologne, D-50931 Cologne, Germany.
FAU - Rose-John, Stefan
AU  - Rose-John S
AUID- ORCID: 0000-0002-7519-3279
AD  - Department for Biochemistry, Christian-Albrechts-University zu Kiel, D-24098 
      Kiel, Germany.
FAU - Garbers, Christoph
AU  - Garbers C
AUID- ORCID: 0000-0003-4939-6950
AD  - Department of Pathology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 
      D-39120 Magdeburg, Germany.
FAU - Muller, Stefan
AU  - Muller S
AD  - Center for Molecular Medicine (CMMC), Proteomics Facility, University of Cologne, 
      D-50931 Cologne, Germany.
FAU - Lackmann, Jan-Wilm
AU  - Lackmann JW
AUID- ORCID: 0000-0001-8182-8034
AD  - Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated 
      Diseases (CECAD), University of Cologne, D-50931 Cologne, Germany.
FAU - Mahabir, Esther
AU  - Mahabir E
AUID- ORCID: 0000-0002-9573-5127
AD  - Comparative Medicine, Center for Molecular Medicine Cologne (CMMC), Faculty of 
      Medicine and University Hospital Cologne, D-50937 Cologne, Germany.
FAU - Dotsch, Jorg
AU  - Dotsch J
AD  - Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and 
      University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany.
FAU - Hucklenbruch-Rother, Eva
AU  - Hucklenbruch-Rother E
AD  - Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and 
      University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany.
FAU - Bae-Gartz, Inga
AU  - Bae-Gartz I
AUID- ORCID: 0000-0002-4061-503X
AD  - Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and 
      University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany.
LA  - eng
GR  - RO 419/2-1/Deutsche Forschungsgemeinschaft/
PT  - Journal Article
DEP - 20211023
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - 0 (Adipokines)
RN  - 0 (Biomarkers)
RN  - 0 (Insulin)
RN  - 0 (Interleukin-6)
RN  - 0 (Proteome)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Adipokines/genetics/metabolism
MH  - Adipose Tissue, White/metabolism
MH  - Animals
MH  - Biomarkers/blood
MH  - Body Weight
MH  - Brain/*metabolism
MH  - Diet
MH  - Diet, Western
MH  - Female
MH  - Glucose Tolerance Test
MH  - Insulin/metabolism
MH  - Interleukin-6/*metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Obesity, Maternal/blood/*metabolism
MH  - Phenotype
MH  - Pregnancy
MH  - Proteome/metabolism
MH  - Proteomics
MH  - RNA, Messenger/genetics/metabolism
MH  - *Signal Transduction
MH  - Mice
PMC - PMC8618896
OTO - NOTNLM
OT  - GFAP (glial fibrillary acidic protein)
OT  - IL-6-trans-signaling
OT  - hypothalamic dysfunction
OT  - maternal nutrition
OT  - newborn nutrition
OT  - perinatal programming
OT  - prevention
OT  - proteomics
OT  - sgp130 (soluble gp130)
OT  - western-style-diet
COIS- The authors declare no conflict of interest.
EDAT- 2021/11/28 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/10/23
CRDT- 2021/11/27 01:29
PHST- 2021/09/01 00:00 [received]
PHST- 2021/10/18 00:00 [revised]
PHST- 2021/10/21 00:00 [accepted]
PHST- 2021/11/27 01:29 [entrez]
PHST- 2021/11/28 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/10/23 00:00 [pmc-release]
AID - nu13113735 [pii]
AID - nutrients-13-03735 [pii]
AID - 10.3390/nu13113735 [doi]
PST - epublish
SO  - Nutrients. 2021 Oct 23;13(11):3735. doi: 10.3390/nu13113735.