Expression of clock gene Dbp in omental and mesenteric adipose tissue in patients with type 2 diabetes
Expression of clock gene Dbp in omental and mesenteric adipose tissue in patients with type 2 diabetes
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DOI：
10.1136/bmjdrc-2020-001465
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发表时间：
2020-08
影响因子：
4.1
通讯作者：
K. Ushijima;Chisato Suzuki;H. Kitamura;Ken Shimada;Hirotoshi Kawata;A. Tanaka;H. Horie;Y. Hosoya;Y. Imai;C. Yamashita;A. Fujimura
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文献类型：
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作者：
K. Ushijima;Chisato Suzuki;H. Kitamura;Ken Shimada;Hirotoshi Kawata;A. Tanaka;H. Horie;Y. Hosoya;Y. Imai;C. Yamashita;A. Fujimura
我们之前在ob/ob小鼠（人类2型糖尿病（DM2）动物模型之一）中报道，（i）附睾脂肪组织中时钟基因Dbp启动子区组蛋白H3赖氨酸9（H3K9）的乙酰化和DBP mRNA表达降低，（ii）DBP与过氧化物酶体增殖物激活受体（Ppar）-γ启动子区的结合和前脂肪细胞中的 PPAR-γ1sv 减少，(iii) 脂联素分泌减少，导致胰岛素敏感性受损。研究设计和方法 本研究旨在评估 DM2 患者是否检测到内脏脂肪组织的这种变化。我们在胃癌和结直肠癌淋巴结清扫术中获得了大网膜和肠系膜脂肪组织，并研究了脂肪组织中的这些变量（胃癌大网膜；13 个非 DM，12 个 DM2；来自结直肠癌的肠系膜；12 个非 DM，11 个 DM2）。结果 DM2 患者 Dbp 启动子区的组蛋白 H3K9 乙酰化以及网膜（但肠系膜脂肪组织中）的 DBP mRNA 表达显着低于非 DM 患者。 DM2 患者的网膜脂肪组织中 PPAR-γ mRNA 表达也较低，但肠系膜脂肪组织中则不然。结论 在糖尿病小鼠中观察到的 DBP-PPAR-γ 轴的变化在 DM2 患者中也可检测到。由于据报道脂联素分泌是通过 PPAR-γ 相关机制增强的，因此本研究支持了网膜脂肪组织参与 DM2 机制的假设。
Introduction We previously reported in ob/ob mice, one of animal models of human type 2 diabetes mellitus (DM2), that (i) acetylation of histone H3 lysine 9 (H3K9) at the promoter region of clock gene Dbp and DBP mRNA expression are reduced in epididymal adipose tissue, (ii) binding of DBP to the promoter region of peroxisome proliferator-activated receptor (Ppar)-γ and mRNA expression of PPAR-γ1sv were decreased in preadipocytes and (iii) adiponectin secretion was decreased, leading to the impaired insulin sensitivity. Research design and methods The present study was undertaken to evaluate whether such the changes in visceral adipose tissue were detected in patients with DM2. We obtained omental and mesenteric adipose tissue during surgery of lymph node dissection for gastric and colorectal cancers, and investigated these variables in adipose tissue (omental from gastric cancer; 13 non-DM, 12 DM2: mesenteric from colorectal cancer; 12 non-DM, 11 DM2). Results Acetylation of histone H3K9 at the promoter region of Dbp and DBP mRNA expression in omental, but not in mesenteric adipose tissue were significantly lower in DM2 than in patients without DM. PPAR-γ mRNA expression in omental adipose tissue was also lower in patients with DM2, but not in mesenteric adipose tissue. Conclusions The changes in DBP-PPAR-γ axis observed in mice with diabetes were also detected in patients with DM2. Because adiponectin secretion is reported to be enhanced through the PPAR-γ-related mechanism, this study supports the hypothesis that omental adipose tissue is involved in the mechanism of DM2.