Brown adipocytes suppress kidney stone formation via heat-producing protein, uncoupling protein 1
Brown adipocytes suppress kidney stone formation via heat-producing protein, uncoupling protein 1
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棕色脂肪细胞通过产热蛋白、解偶联蛋白 1 抑制肾结石形成
DOI：
10.1097/ju.0000000000000824.09
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
and Yasui T.
中科院分区：
文献类型：
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作者：
Sugino T;Tanaka Y;Unno R;Taguchi K;Hamamoto S;Ando R;Okada A;Mogami T;Yamashita H;and Yasui T.
方法：研究1：9周龄雄性C57BL/6小鼠接受假手术或棕色脂肪组织移植手术（假手术组、移植组，每组n=6）。手术后三周，通过每日腹内注射 80 mg/kg 乙醛酸盐 (GOX) 引入肾晶体沉积物。研究2：通过每日腹内注射80 mg/kg GOX引入野生型和缺陷型8周龄雄性UCP1缺陷小鼠(B6.129-Ucp1 tm1Kz/J)(WT组、KO组，每组n=6)肾晶体沉积。两项研究均采集了小鼠的脂肪组织、肾脏和24小时尿液样本。 结果：研究1：移植组肾晶体沉积量显着低于假手术组（3.28倍）（图1a），并且炎症标志物表达较低，如趋化因子（CC基序）配体2（Ccl2）、含有EGF模块的粘蛋白样 在肾脏中观察到受体 1 (Emr1)、肿瘤坏死因子 (Tnf) 和分泌性磷蛋白 1 (Spp1)。移植组肾周脂肪组织中可见诱导性棕色脂肪细胞。研究2：KO组肾晶体沉积量显着高于WT组（3.28倍）（图1b），并且肾脏中观察到Emr1、Tnf和Spp1的表达较高。在 KO 组的棕色脂肪组织中强烈观察到炎症细胞的浸润。两项研究中24小时尿液样本没有显着差异。结论：棕色脂肪组织移植通过抗炎作用抑制肾晶体形成，UCP1在该机制中是必要的。棕色脂肪细胞可以成为肾结石形成的治疗靶点。
METHODS:Study 1: Nine-week-old male C57BL/6 mice underwent sham or brown adipose tissue transplant surgery (sham group, transplant group, n= 6 in each group). Three weeks after surgery, renal crystal deposits were introduced via daily intra-abdominal injections of 80 mg/kg glyoxylate (GOX). Study 2: Renal crystal deposits were introduced via daily intra-abdominal injections of 80 mg/kg GOX in wild-type and defective type 8-week-old male UCP1-deficient mice (B6. 129-Ucp1 tm1Kz/J)(WT group, KO group, n= 6 in each group). Fat tissues, kidneys, and 24-hour urine samples of the mice were collected in both studies.RESULTS:Study 1: In the transplant group, the amount of renal crystal deposits was significantly lower (3.28 times) than that in the sham group (Fig. 1a), and lower expression of inflammatory markers, such as chemokine (CC motif) ligand 2 (Ccl2), EGF module-containing mucin-like receptor 1 (Emr1), tumor necrosis factor (Tnf), and secreted phosphoprotein 1 (Spp1) was observed in the kidney. Inductive brown adipocytes were observed in the perirenal fat tissue in the transplant group. Study 2: In the KO group, the amount of renal crystal deposits was significantly higher (3.28 times) than that in the WT group (Fig. 1b), and higher expression of Emr1, Tnf, and Spp1 was observed in the kidney. Infiltration of inflammatory cells was strongly observed in brown adipose tissue in the KO group. There were no significant differences in the 24-hour urine samples throughout the two studies.CONCLUSIONS:Brown adipose tissue transplantation suppressed renal crystal formation via anti-inflammatory effects, and UCP1 would be necessary in this mechanism. Brown adipocytes can be the therapeutic target for kidney stone formation.