PMID- 32272237
OWN - NLM
STAT- MEDLINE
DCOM- 20210706
LR  - 20210706
IS  - 2212-8778 (Electronic)
IS  - 2212-8778 (Linking)
VI  - 37
DP  - 2020 Jul
TI  - Maternal high-fat diet exaggerates diet-induced insulin resistance in adult 
      offspring by enhancing inflammasome activation through noncanonical pathway of 
      caspase-11.
PG  - 100988
LID - S2212-8778(20)30062-4 [pii]
LID - 10.1016/j.molmet.2020.100988 [doi]
LID - 100988
AB  - OBJECTIVE: Maternal high-fat diet (HFD) has been shown to promote the development 
      of insulin resistance (IR) in adult offspring; however, the underlying mechanisms 
      remain unclear. METHODS: Eight-week-old female wild-type mice (C57BL/6) were fed 
      either an HFD or a normal diet (ND), one week prior to mating, and the diet was 
      continued throughout gestation and lactation. Eight-week-old male offspring of 
      both groups were fed an HFD for 8 weeks. RESULTS: Offspring of HFD-fed dams 
      (O-HFD) exhibited significantly impaired insulin sensitivity compared with the 
      offspring of ND-fed dams (O-ND). The adipocyte size of the eWAT increased 
      significantly in O-HFD and was accompanied by abundant crown-like structures 
      (CLSs), as well as a higher concentration of interleukin 1beta (IL-1beta) in the eWAT. 
      Treatment with an inflammasome inhibitor, MCC950, completely abrogated the 
      enhanced IR in O-HFD. However, ex vivo caspase-1 activity in eWAT revealed no 
      difference between the two groups. In contrast, noncanonical inflammasome 
      activation of caspase-11 was significantly augmented in O-HFD compared with O-ND, 
      suggesting that membrane pore formation, but not cleavage of pro-IL-1beta by 
      caspase-1, is augmented in O-HFD. To examine the membrane pore formation, we 
      performed metabolic activation of bone marrow-derived macrophages (BMDMs). The 
      percentage of pore formation assessed by ethidium bromide staining was 
      significantly higher in BMDMs of O-HFD, accompanied by an enhanced active 
      caspase-11 expression. Consistently, the concentration of IL-1beta in culture 
      supernatants was significantly higher in the BMDMs from O-HFD than those from 
      O-ND. CONCLUSIONS: These findings demonstrate that maternal HFD exaggerates 
      diet-induced IR in adult offspring by enhancing noncanonical caspase-11-mediated 
      inflammasome activation.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.
FAU - Wada, Naotoshi
AU  - Wada N
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Yamada, Hiroyuki
AU  - Yamada H
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan. Electronic address: 
      hiyamada@koto.kpu-m.ac.jp.
FAU - Motoyama, Shinichiro
AU  - Motoyama S
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Saburi, Makoto
AU  - Saburi M
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Sugimoto, Takeshi
AU  - Sugimoto T
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Kubota, Hiroshi
AU  - Kubota H
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Miyawaki, Daisuke
AU  - Miyawaki D
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Wakana, Noriyuki
AU  - Wakana N
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Kami, Daisuke
AU  - Kami D
AD  - Department of Regenerative Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Ogata, Takehiro
AU  - Ogata T
AD  - Department of Pathology and Cell Regulation, Graduate School of Medical Science, 
      Kyoto Prefectural University of Medicine, Kyoto, Japan.
FAU - Matoba, Satoaki
AU  - Matoba S
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200406
PL  - Germany
TA  - Mol Metab
JT  - Molecular metabolism
JID - 101605730
RN  - 0 (Cytokines)
RN  - 0 (Inflammasomes)
RN  - 0 (Insulin)
RN  - EC 3.4.22.- (Casp4 protein, mouse)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.22.- (Caspases, Initiator)
SB  - IM
MH  - Animals
MH  - Caspases/metabolism
MH  - Caspases, Initiator/*metabolism/physiology
MH  - Cytokines/metabolism
MH  - Diet, High-Fat/adverse effects
MH  - Female
MH  - Inflammasomes/*metabolism/physiology
MH  - Insulin/metabolism
MH  - Insulin Resistance/*physiology
MH  - Macrophages/metabolism
MH  - Male
MH  - Maternal Exposure
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Obesity
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/metabolism
PMC - PMC7210595
OTO - NOTNLM
OT  - Caspase-1
OT  - Caspase-11
OT  - Inflammasome
OT  - Insulin resistance
OT  - Interleukin-1beta
OT  - Maternal high-fat diet
EDAT- 2020/04/10 06:00
MHDA- 2021/07/07 06:00
PMCR- 2020/04/06
CRDT- 2020/04/10 06:00
PHST- 2020/02/08 00:00 [received]
PHST- 2020/03/22 00:00 [revised]
PHST- 2020/03/31 00:00 [accepted]
PHST- 2020/04/10 06:00 [pubmed]
PHST- 2021/07/07 06:00 [medline]
PHST- 2020/04/10 06:00 [entrez]
PHST- 2020/04/06 00:00 [pmc-release]
AID - S2212-8778(20)30062-4 [pii]
AID - 100988 [pii]
AID - 10.1016/j.molmet.2020.100988 [doi]
PST - ppublish
SO  - Mol Metab. 2020 Jul;37:100988. doi: 10.1016/j.molmet.2020.100988. Epub 2020 Apr 
      6.