TLR2-Deficiency Promotes Prenatal LPS Exposure-Induced Offspring Hyperlipidemia
Toll-like receptor 2 (TLR2), which recognizes several lipopeptides and transduces inflammatory signaling, promotes the pathogenesis of diet-induced dyslipidemia and obesity. TLR2-deficient mice were shown to have improved insulin sensitivity and reduced diet-induced metabolic syndrome. Previous stud...
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doaj-a965bc71cdb3484589fff9d322d726eb2020-11-25T01:57:17ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-08-011010.3389/fphys.2019.01102464750TLR2-Deficiency Promotes Prenatal LPS Exposure-Induced Offspring HyperlipidemiaDayan Cao0Wenjia Wang1Shuhui Li2Wenjing Lai3Xiaoyong Huang4Jianzhi Zhou5Xin Chen6Xiaohui Li7Institute of Materia Medica, Department of Pharmaceutics, College of Pharmacy, Army Medical University, Chongqing, ChinaInstitute of Materia Medica, Department of Pharmaceutics, College of Pharmacy, Army Medical University, Chongqing, ChinaDepartment of Clinical Biochemistry, College of Pharmacy, Army Medical University, Chongqing, ChinaDepartment of Pharmacy, Xinqiao Hospital, Army Medical University, Chongqing, ChinaInstitute of Immunology, PLA, Army Medical University, Chongqing, ChinaInstitute of Materia Medica, Department of Pharmaceutics, College of Pharmacy, Army Medical University, Chongqing, ChinaInstitute of Materia Medica, Department of Pharmaceutics, College of Pharmacy, Army Medical University, Chongqing, ChinaInstitute of Materia Medica, Department of Pharmaceutics, College of Pharmacy, Army Medical University, Chongqing, ChinaToll-like receptor 2 (TLR2), which recognizes several lipopeptides and transduces inflammatory signaling, promotes the pathogenesis of diet-induced dyslipidemia and obesity. TLR2-deficient mice were shown to have improved insulin sensitivity and reduced diet-induced metabolic syndrome. Previous studies demonstrated that prenatal lipopolysaccharide (LPS) exposure causes dyslipidemia accompanied by increased body weight and insulin resistance in offspring. To determine whether TLRs are involved in this complex abnormal phenotype, we analyzed TLR2 and TLR4 expression levels in adipose tissues from offspring with prenatal LPS-exposure (offspring-pLPS) and compared these levels to those of control offspring with prenatal saline-exposure (offspring-pSaline). TLR2 expression was specifically upregulated in the adipose tissue of offspring-pLPS mice. However, unexpectedly, TLR2-deficient offspring-pLPS mice not only presented with an abnormal phenotype comparable to that of wild-type offspring-pLPS mice but also exhibited significantly more severe hyperlipidemia. Our further analyses revealed a dramatic upregulation of TLR4 expression and overactivation of the TLR4/Myd88 signaling pathway in TLR2-deficient offspring-pLPS adipose tissue. Our finding suggests a compensatory genetic interaction between TLR2 and TLR4 in the context of prenatal inflammatory stimulation, and this interaction likely contributes to the prenatal inflammation-induced hyperlipidemia and lipid overload-induced obesity, thus providing a potential mechanism for the fetal origin of adult metabolic diseases.https://www.frontiersin.org/article/10.3389/fphys.2019.01102/fullhyperlipidemiaprenatal lipopolysaccharide stimulationTLR2TLR4VLDLR |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dayan Cao Wenjia Wang Shuhui Li Wenjing Lai Xiaoyong Huang Jianzhi Zhou Xin Chen Xiaohui Li |
spellingShingle |
Dayan Cao Wenjia Wang Shuhui Li Wenjing Lai Xiaoyong Huang Jianzhi Zhou Xin Chen Xiaohui Li TLR2-Deficiency Promotes Prenatal LPS Exposure-Induced Offspring Hyperlipidemia Frontiers in Physiology hyperlipidemia prenatal lipopolysaccharide stimulation TLR2 TLR4 VLDLR |
author_facet |
Dayan Cao Wenjia Wang Shuhui Li Wenjing Lai Xiaoyong Huang Jianzhi Zhou Xin Chen Xiaohui Li |
author_sort |
Dayan Cao |
title |
TLR2-Deficiency Promotes Prenatal LPS Exposure-Induced Offspring Hyperlipidemia |
title_short |
TLR2-Deficiency Promotes Prenatal LPS Exposure-Induced Offspring Hyperlipidemia |
title_full |
TLR2-Deficiency Promotes Prenatal LPS Exposure-Induced Offspring Hyperlipidemia |
title_fullStr |
TLR2-Deficiency Promotes Prenatal LPS Exposure-Induced Offspring Hyperlipidemia |
title_full_unstemmed |
TLR2-Deficiency Promotes Prenatal LPS Exposure-Induced Offspring Hyperlipidemia |
title_sort |
tlr2-deficiency promotes prenatal lps exposure-induced offspring hyperlipidemia |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2019-08-01 |
description |
Toll-like receptor 2 (TLR2), which recognizes several lipopeptides and transduces inflammatory signaling, promotes the pathogenesis of diet-induced dyslipidemia and obesity. TLR2-deficient mice were shown to have improved insulin sensitivity and reduced diet-induced metabolic syndrome. Previous studies demonstrated that prenatal lipopolysaccharide (LPS) exposure causes dyslipidemia accompanied by increased body weight and insulin resistance in offspring. To determine whether TLRs are involved in this complex abnormal phenotype, we analyzed TLR2 and TLR4 expression levels in adipose tissues from offspring with prenatal LPS-exposure (offspring-pLPS) and compared these levels to those of control offspring with prenatal saline-exposure (offspring-pSaline). TLR2 expression was specifically upregulated in the adipose tissue of offspring-pLPS mice. However, unexpectedly, TLR2-deficient offspring-pLPS mice not only presented with an abnormal phenotype comparable to that of wild-type offspring-pLPS mice but also exhibited significantly more severe hyperlipidemia. Our further analyses revealed a dramatic upregulation of TLR4 expression and overactivation of the TLR4/Myd88 signaling pathway in TLR2-deficient offspring-pLPS adipose tissue. Our finding suggests a compensatory genetic interaction between TLR2 and TLR4 in the context of prenatal inflammatory stimulation, and this interaction likely contributes to the prenatal inflammation-induced hyperlipidemia and lipid overload-induced obesity, thus providing a potential mechanism for the fetal origin of adult metabolic diseases. |
topic |
hyperlipidemia prenatal lipopolysaccharide stimulation TLR2 TLR4 VLDLR |
url |
https://www.frontiersin.org/article/10.3389/fphys.2019.01102/full |
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