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Endotoxemia by Porphyromonas gingivalis Alters Endocrine Functions in Brown Adipose Tissue
Frontiers in Cellular and Infection Microbiology ( IF 5.7 ) Pub Date : 2020-12-03 , DOI: 10.3389/fcimb.2020.580577
Masahiro Hatasa 1 , Yujin Ohsugi 1 , Sayaka Katagiri 1 , Sumiko Yoshida 1 , Hiromi Niimi 1 , Kazuki Morita 1 , Yosuke Tsuchiya 1 , Tsuyoshi Shimohira 1 , Naoki Sasaki 2 , Shogo Maekawa 1 , Takahiko Shiba 1 , Tomomitsu Hirota 3 , Haruka Tohara 4 , Hirokazu Takahashi 5, 6 , Hiroshi Nitta 2 , Takanori Iwata 1
Affiliation  

Improvement of obesity is important for increasing longevity. The characteristics, size, and function of adipocytes are altered in patients with obesity. Adipose tissue is not only an energy storage but also an endocrine organ. Alteration of endocrine activities in adipose tissue, among them the functional decline of brown adipose tissue (BAT), is associated with obesity. Periodontal disease is a risk factor for systemic diseases since endotoxemia is caused by periodontal bacteria. However, the effect of periodontal disease on obesity remains unclear. Thus, this study aimed to investigate the effect of endotoxemia due to Porphyromonas gingivalis, a prominent cause of periodontal disease, on the BAT. Herein, endotoxemia was induced in 12-week-old C57BL/6J mice through intravenous injection of sonicated 108 CFU of P. gingivalis (Pg) or saline (control [Co]) once. Eighteen hours later, despite no inflammatory M1 macrophage infiltration, inflammation-related genes were upregulated exclusively in the BAT of Pg mice compared with Co mice. Although no marked histological changes were observed in adipose tissues, expressions of genes related to lipolysis, Lipe and Pnpla2 were downregulated after P. gingivalis injection in BAT. Furthermore, expression of Pparg and Adipoq was downregulated only in the BAT but not in the white adipose tissues, along with downregulation of Ucp1 and Cidea expression, which are BAT-specific markers, in Pg mice. Microarray analysis of the BAT showed 106 differentially expressed genes between Co and Pg mice. Gene set enrichment analysis revealed that the cholesterol homeostasis gene set and PI3/Akt/mTOR signaling gene set in BAT were downregulated, whereas the TGF-β signaling gene set was enriched in Pg mice. Overall, intravenous injection of sonicated P. gingivalis altered the endocrine functions of the BAT in mice. This study indicates that endotoxemia by P. gingivalis potentially affects obesity by disrupting BAT function.



中文翻译:

牙龈卟啉单胞菌的内毒素血症改变棕色脂肪组织的内分泌功能

肥胖的改善对于延长寿命很重要。肥胖患者的脂肪细胞的特征,大小和功能会改变。脂肪组织不仅是能量储存器,而且还是内分泌器官。肥胖组织中内分泌活动的改变(其中棕色脂肪组织(BAT)的功能下降)与肥胖有关。牙周疾病是全身性疾病的危险因素,因为内毒素血症是由牙周细菌引起的。然而,牙周病对肥胖的影响仍不清楚。因此,本研究旨在调查因牙龈卟啉单胞菌是BAT上牙周疾病的重要原因。在此,通过静脉内注射10 8 CFU的超声波处理的12周龄C57BL / 6J小鼠,可诱发内毒素血症牙龈卟啉单胞菌(Pg)或盐水(对照[Co])一次。18小时后,尽管没有炎症性M1巨噬细胞浸润,但是与Co小鼠相比,Pg小鼠的BAT中仅与炎症相关的基因上调。尽管在脂肪组织中未观察到明显的组织学变化,但与脂肪分解相关的基因表达,利佩Pnpla2 被下调后 牙龈卟啉单胞菌BAT中注射。此外,表达帕帕格阿迪波克 仅在BAT中被下调,而在白色脂肪组织中未下调, Ucp1赛迪亚是Pg小鼠中BAT特异性标记的表达。BAT的微阵列分析显示Co和Pg小鼠之间有106个差异表达的基因。基因集富集分析显示,BAT中的胆固醇稳态基因集和PI3 / Akt / mTOR信号转导基因集被下调,而Tg-β信号转导基因集在Pg小鼠中富集。总体而言,超声静脉注射牙龈卟啉单胞菌改变了BAT的内分泌功能。这项研究表明内毒素血症通过牙龈卟啉单胞菌 通过破坏BAT功能可能会影响肥胖。

更新日期:2021-01-19
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