Prepubertal obesity (PPO) is growing at an alarming rate and is now considered a risk factor for renal injury. Recently, we reported that the early development of renal injury in obese Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) rats was associated with increased T-cell infiltration and activation prior to puberty. Therefore, the current study investigated the effect of inhibiting T-cell activation with abatacept on the progression of renal injury in young obese SSLepRmutant rats before puberty. Four-week-old SS and SSLepRmutant rats were treated with IgG or abatacept (1 mg/kg; ip, every other day) for 4 weeks. Abatacept reduced the renal infiltration of T-cells by almost 50% in SSLepRmutant rats. Treatment with abatacept decreased the renal expression of macrophage inflammatory protein-3 alpha (MIP-3α) while increasing IL-4 in SSLepRmutant rats without affecting SS rats. While not having an impact on blood glucose, abatacept reduced hyperinsulinemia and plasma triglycerides in SSLepRmutant rats without affecting SS rats. We did not observe any differences in MAP among the groups. Proteinuria was markedly higher in SSLepRmutant rats versus SS rats throughout the study, and treatment with abatacept decreased proteinuria by about 40% in SSLepRmutant rats without affecting SS rats. We observed significant increases in glomerular and tubular injury and renal fibrosis in SSLepRmutant rats vs SS rats, and chronic treatment with abatacept significantly reduced these renal abnormalities in SSLepRmutant rats. These data suggest that renal T-cell activation contributes to the early progression of renal injury associated with PPO.

中文翻译：

---

阿巴西普可减少青春期前肥胖 Dahl 盐敏感大鼠的肾脏 T 细胞浸润和肾脏炎症，并改善进行性肾损伤。

青春期前肥胖（PPO）正在以惊人的速度增长，目前被认为是肾损伤的危险因素。最近，我们报道了肥胖 Dahl 盐敏感性瘦素受体突变体 (SSLepRmutant) 大鼠早期肾损伤的发生与青春期前 T 细胞浸润和激活的增加有关。因此，本研究调查了用阿巴西普抑制T细胞活化对青春期前年轻肥胖SSLepR突变大鼠肾损伤进展的影响。用 IgG 或阿巴西普（1 mg/kg；腹膜内注射，每隔一天）治疗 4 周龄的 SS 和 SSLepR 突变大鼠 4 周。在 SSLepR 突变大鼠中，阿巴西普使 T 细胞的肾脏浸润减少了近 50%。阿巴西普治疗降低了 SSLepR 突变大鼠肾脏巨噬细胞炎症蛋白 3 α (MIP-3α) 的表达，同时增加了 IL-4，但不影响 SS 大鼠。虽然对血糖没有影响，但阿巴西普降低了 SSLepR 突变大鼠的高胰岛素血症和血浆甘油三酯，而不影响 SS 大鼠。我们没有观察到各组间 MAP 存在任何差异。在整个研究过程中，SSLepR 突变型大鼠的蛋白尿明显高于 SS 大鼠，并且阿巴西普治疗使 SSLepR 突变型大鼠的蛋白尿降低了约 40%，而对 SS 大鼠没有影响。我们观察到 SSLepR 突变大鼠与 SS 大鼠相比，肾小球和肾小管损伤以及肾纤维化显着增加，并且阿巴西普长期治疗显着减少了 SSLepR 突变大鼠的这些肾脏异常。这些数据表明肾 T 细胞激活有助于 PPO 相关肾损伤的早期进展。