Limited effects of systemic or renal lipoprotein lipase deficiency on renal physiology and diseases
Limited effects of systemic or renal lipoprotein lipase deficiency on renal physiology and diseases
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DOI：
10.1016/j.bbrc.2022.06.067
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发表时间：
2022-06-27
影响因子：
3.1
通讯作者：
Kume, Shinji
中科院分区：
文献类型：
--
作者：
Fujino, Yoshihiko;Yasuda-Yamahara, Mako;Kume, Shinji
脂蛋白脂酶（LPL）是一种催化循环甘油三酯水解和脂肪酸转运到细胞中的酶。它的活性受胰岛素的正向调节，胰岛素抵抗与低LPL活性和随后的高脂血症有关。慢性肾脏病（CKD）中高胆固醇血症的参与在临床环境中仍处于争论之中。因此，我们的目的是研究高脂血症在疾病中的作用，使用小鼠全身或肾脏特异性LPL缺乏。系统性LPL缺乏症的特征是高甘油三酯血症，而不是肾损伤或血脂异常相关疾病，例如脂肪肝。此外，LPL缺乏诱导的高脂血症与CKD表型恶化或动脉粥样硬化无关，即使是5/6肾切除诱导的CKD。接下来，因为LPL介导的脂肪酸摄取对于近端肾小管上皮细胞（PTEC）中的能量代谢可能是重要的，所以通过产生在PTEC中特异性缺乏LPL的小鼠来研究肾LPL在肾生理学中的作用。这些小鼠的组织学或肾脏对小分子的重吸收没有异常。这些结果表明，LPL缺乏引起的全身和肾脏脂质异常不会导致或加重肾损伤的发展，并提供了新的见解，关于脂肪毒性在肥胖相关的肾损伤的发病机制中的潜在作用。(c)2022爱思唯尔公司All rights reserved.
Lipoprotein lipase (LPL) is an enzyme that catalyzes the hydrolysis of circulating triglyceride and the transport of fatty acids into cells. Its activity is positively regulated by insulin, and insulin resistance is associated with low LPL activity and subsequent hypertriglyceridemia. The involvement of hyper-triglyceridemia in chronic kidney disease (CKD) is still under the debate in a clinical setting. Therefore, we aimed to study the role of hypertriglyceridemia in the disease using mice with systemic or renal -specific LPL deficiency. Systemic LPL deficiency was characterized by hypertriglyceridemia, but not renal injury or dyslipidemia-related conditions, such as fatty liver. Furthermore, the LPL deficiency -induced hypertriglyceridemia was not associated with a worsening of the CKD phenotype or athero-sclerosis, even when CKD was induced by 5/6 nephrectomy. Next, because LPL-mediated fatty acid up-take may be important for energy metabolism in proximal tubular epithelial cells (PTECs), the role of renal LPL in renal physiology was studied by generating mice lacking LPL specifically in PTECs. These mice showed no abnormalities in their histology or renal reabsorption of micro molecules. These findings suggest that systemic and renal lipid abnormalities caused by LPL deficiency do not cause or worsen the development of renal injury, and provide novel insight regarding the potential role of lipotoxicity in the pathogenesis of obesity-related kidney injury. (c) 2022 Elsevier Inc. All rights reserved.