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Abstract：
Hypoadiponectinemia is the important cause of insulin resistance. Recent studies have shown that periodontitis is associated with hypoadiponectinemia. The purpose of this study was to investigate the effect of periodontitis-induced endoplasmic reticulum stress (ERS) in visceral adipocytes on hypoadiponectinemia.
Rat periodontitis models were established by local ligation with silk around the bilateral maxillary second molars. Porphyromonas gingivalis-lipopolysaccharid (P.g-LPS) was also used to stimulate the visceral adipocytes in vitro. The protein expression levels of glucose regulated protein 78 (GRP78), inositol-requiring protein 1α (IRE1α), protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6) and adiponectin were detected. IRE1α lentiviruses were transfected into visceral adipocytes in vitro, and an IRE1α inhibitor (KIRA6) was injected in epididymal adipose tissue of rats to detect and verify the effect of ERS on adiponectin expression in visceral adipocytes in vivo.
Hypoadiponectinemia was observed in periodontitis rat, and the expression levels of ERS key proteins GRP78 and the phosphorylation levels of IRE1α (p-IRE1α)/IRE1α in visceral adipocytes were increased, while the expression levels of adiponectin protein were decreased. After KIRA6 injection into epididymal adipose tissue of rats with periodontitis, adiponectin levels in visceral adipocytes increased, and serum adiponectin levels recovered to a certain extent. The protein expression levels of GRP78 and p-IRE1α/IRE1α were increased and adiponectin protein expression was decreased in P.g-LPS-induced visceral adipocytes. Overexpression of IRE1α further inhibited adiponectin expression in P.g-LPS-stimulated visceral adipocytes, and conversely, IRE1α inhibition restored adiponectin expression.
Our findings suggest that periodontitis induces ERS in visceral adipocytes leading to hypoadiponectinemia. IRE1α is a key protein regulating adiponectin expression in visceral adipocytes.
Rat periodontitis models were established by local ligation with silk around the bilateral maxillary second molars. Porphyromonas gingivalis-lipopolysaccharid (P.g-LPS) was also used to stimulate the visceral adipocytes in vitro. The protein expression levels of glucose regulated protein 78 (GRP78), inositol-requiring protein 1α (IRE1α), protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6) and adiponectin were detected. IRE1α lentiviruses were transfected into visceral adipocytes in vitro, and an IRE1α inhibitor (KIRA6) was injected in epididymal adipose tissue of rats to detect and verify the effect of ERS on adiponectin expression in visceral adipocytes in vivo.
Hypoadiponectinemia was observed in periodontitis rat, and the expression levels of ERS key proteins GRP78 and the phosphorylation levels of IRE1α (p-IRE1α)/IRE1α in visceral adipocytes were increased, while the expression levels of adiponectin protein were decreased. After KIRA6 injection into epididymal adipose tissue of rats with periodontitis, adiponectin levels in visceral adipocytes increased, and serum adiponectin levels recovered to a certain extent. The protein expression levels of GRP78 and p-IRE1α/IRE1α were increased and adiponectin protein expression was decreased in P.g-LPS-induced visceral adipocytes. Overexpression of IRE1α further inhibited adiponectin expression in P.g-LPS-stimulated visceral adipocytes, and conversely, IRE1α inhibition restored adiponectin expression.
Our findings suggest that periodontitis induces ERS in visceral adipocytes leading to hypoadiponectinemia. IRE1α is a key protein regulating adiponectin expression in visceral adipocytes.
摘要：
背景：低脂联素血症是胰岛素抵抗的重要原因。最近的研究表明牙周炎与低脂联素血症有关。目的探讨牙周炎诱导的内脏脂肪细胞内质网应激(ERS)对低脂联素血症的影响。
方法：采用双侧上颌第二磨牙周围丝局部结扎法建立大鼠牙周炎模型。牙龈卟啉单胞菌-脂多糖（P.g-LPS）也用于体外刺激内脏脂肪细胞。葡萄糖调节蛋白78(GRP78)的蛋白表达水平,需要肌醇的蛋白质1α（IRE1α），蛋白激酶RNA样ER激酶（PERK），激活转录因子6(ATF6)和脂联素检测。IRE1α慢病毒体外转染内脏脂肪细胞,并在大鼠附睾脂肪组织中注射IRE1α抑制剂（KIRA6），检测并验证ERS对体内内脏脂肪细胞脂联素表达的影响。
结果：在牙周炎大鼠中观察到低脂联素血症，内脏脂肪细胞中ERS关键蛋白GRP78的表达水平和IRE1α(p-IRE1α)/IRE1α的磷酸化水平升高,脂联素蛋白表达水平降低。将KIRA6注射入牙周炎大鼠附睾脂肪组织后，内脏脂肪细胞的脂联素水平升高，血清脂联素水平有一定程度的恢复。P.g-LPS诱导的内脏脂肪细胞中GRP78和p-IRE1α/IRE1α的蛋白表达水平升高，脂联素蛋白表达降低。IRE1α的过表达进一步抑制P.g-LPS刺激的内脏脂肪细胞中脂联素的表达，反过来,IRE1α抑制可恢复脂联素表达。
结论：我们的研究结果表明牙周炎在内脏脂肪细胞中诱导ERS，导致低脂联素血症。IRE1α是调节内脏脂肪细胞脂联素表达的关键蛋白。
方法：采用双侧上颌第二磨牙周围丝局部结扎法建立大鼠牙周炎模型。牙龈卟啉单胞菌-脂多糖（P.g-LPS）也用于体外刺激内脏脂肪细胞。葡萄糖调节蛋白78(GRP78)的蛋白表达水平,需要肌醇的蛋白质1α（IRE1α），蛋白激酶RNA样ER激酶（PERK），激活转录因子6(ATF6)和脂联素检测。IRE1α慢病毒体外转染内脏脂肪细胞,并在大鼠附睾脂肪组织中注射IRE1α抑制剂（KIRA6），检测并验证ERS对体内内脏脂肪细胞脂联素表达的影响。
结果：在牙周炎大鼠中观察到低脂联素血症，内脏脂肪细胞中ERS关键蛋白GRP78的表达水平和IRE1α(p-IRE1α)/IRE1α的磷酸化水平升高,脂联素蛋白表达水平降低。将KIRA6注射入牙周炎大鼠附睾脂肪组织后，内脏脂肪细胞的脂联素水平升高，血清脂联素水平有一定程度的恢复。P.g-LPS诱导的内脏脂肪细胞中GRP78和p-IRE1α/IRE1α的蛋白表达水平升高，脂联素蛋白表达降低。IRE1α的过表达进一步抑制P.g-LPS刺激的内脏脂肪细胞中脂联素的表达，反过来,IRE1α抑制可恢复脂联素表达。
结论：我们的研究结果表明牙周炎在内脏脂肪细胞中诱导ERS，导致低脂联素血症。IRE1α是调节内脏脂肪细胞脂联素表达的关键蛋白。
