Sugino Teruaki, Okada Atsushi, Taguchi Kazumi, Unno Rei, Hamamoto Shuzo, Ando Ryosuke, Mogami Tohru, Kohri Kenjiro, Yamashita Hitoshi, Yasui Takahiro
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan.
Department of Urology, JA Mie Komono Kosei Hospital , Mie , Japan.
Am J Physiol Renal Physiol. 2019 Jun 1;316(6):F1282-F1292. doi: 10.1152/ajprenal.00523.2018. Epub 2019 Apr 17.
According to recent studies, kidney stones are associated with metabolic syndrome. We focused on brown adipocytes and β-stimulant-induced brown-like adipocytes to investigate how these adipocytes influence kidney stone disease. For the interscapular brown adipose tissue (iBAT) removal experiment, mice were subjected to either iBAT removal or sham operation (X-BAT group or sham group), and, after 3 wk, renal crystal deposition was induced by intra-abdominal injection of glyoxylate (GOX) for 6 days. For the β-stimulant experiment, mice were administered intra-abdominal injections of the β-stimulant (β-group) or saline (control group) for 6 days. Thereafter, renal crystal deposition was induced by intra-abdominal injection of GOX for 6 days. iBAT removal decreased the expression of and increased that of chemokine (C-C motif) ligand 2 (), EGF module-containing mucin-like receptor 1 (), and tumor necrosis factor () in the kidneys. Renal crystal deposition was 2.06-fold higher in the X-BAT group than in the sham group. The β-stimulant caused differentiation of white adipocytes into brown-like adipocytes. In the kidneys of the β-group, the expression of and decreased and that of increased. Renal crystal deposition was 0.17-fold lower in the β-group than in the control group. In summary, iBAT removal promoted kidney inflammation and renal crystal formation. β-Stimulant-induced brown-like adipocytes reduced inflammation and improved antioxidant action in the kidneys, which suppressed renal crystal formation. This is the first report on the therapeutic role of brown and brown-like adipocytes for kidney stone formation.
根据最近的研究，肾结石与代谢综合征有关。我们聚焦于棕色脂肪细胞和β-激动剂诱导的棕色样脂肪细胞，以研究这些脂肪细胞如何影响肾结石疾病。对于肩胛间棕色脂肪组织（iBAT）切除实验，将小鼠分为iBAT切除组或假手术组（X-BAT组或假手术组），3周后，通过腹腔注射乙醛酸（GOX）6天诱导肾晶体沉积。对于β-激动剂实验，给小鼠腹腔注射β-激动剂（β组）或生理盐水（对照组）6天。此后，通过腹腔注射GOX 6天诱导肾晶体沉积。iBAT切除降低了肾脏中 的表达，并增加了趋化因子（C-C基序）配体2（ ）、含EGF模块的粘蛋白样受体1（ ）和肿瘤坏死因子（ ）的表达。X-BAT组的肾晶体沉积比假手术组高2.06倍。β-激动剂导致白色脂肪细胞分化为棕色样脂肪细胞。在β组小鼠的肾脏中， 和 的表达降低，而 的表达增加。β组的肾晶体沉积比对照组低至0.17倍。总之，iBAT切除促进了肾脏炎症和肾晶体形成。β-激动剂诱导的棕色样脂肪细胞减轻了炎症并改善了肾脏中的抗氧化作用，从而抑制了肾晶体形成。这是关于棕色和棕色样脂肪细胞对肾结石形成的治疗作用的首次报道。
