TLR2-Deficiency Promotes Prenatal LPS Exposure-Induced Offspring Hyperlipidemia
| Autor: | Xin Chen, Shuhui Li, Wenjing Lai, Dayan Cao, Jianzhi Zhou, Xiaoyong Huang, Xiaohui Li, Wen-jia Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Offspring Physiology Adipose tissue lcsh:Physiology 03 medical and health sciences 0302 clinical medicine Insulin resistance Downregulation and upregulation Internal medicine Physiology (medical) Hyperlipidemia medicine hyperlipidemia TLR2 TLR4 Original Research Fetus lcsh:QP1-981 business.industry VLDLR medicine.disease prenatal lipopolysaccharide stimulation 030104 developmental biology Endocrinology Metabolic syndrome business 030217 neurology & neurosurgery Dyslipidemia |
| Zdroj: | Frontiers in Physiology, Vol 10 (2019) Frontiers in Physiology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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