Ha Sugyeong, Kim Min Jo, Kim Dae Hyun, Kim Byeong Moo, Chung Ki Wung, Chung Hae Young
College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.
College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea; Division of Natural Drug Discovery, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Exp Gerontol. 2020 Dec;142:111108. doi: 10.1016/j.exger.2020.111108. Epub 2020 Oct 30.
Age- or high fat diet (HFD)-associated renal structural changes are commonly associated with a decline in renal function. Although HFD causes injurious effects in various organs during aging, its effects on age-associated renal fibrosis have not yet been investigated. In this study, we show that a short-term HFD significantly induces renal fibrosis by causing loss of mitochondrial integrity in aged Sprague-Dawley (SD) rats. To evaluate the effects of short-term HFD intake on age-associated renal fibrosis, we administered HFD in young and aged SD rats for 15 days. Our results showed that a short-term HFD significantly increased the renal fibrosis and inflammation in aged rats. Moreover, mitochondrial integrity and the expression of fatty acid oxidation-related proteins decreased in the kidneys of the HFD-fed aged rats. Further, NRK52E renal tubular epithelial cells subjected to lipid stress by treatment with oleic acid showed a reduced amount of mitochondrial OXPHOS-related proteins. Our results suggest that short-term HFD affects mitochondrial integrity and exacerbates inflammation leading to renal fibrosis, especially in aged rats. We conclude that the mitochondrial integrity in kidney tissues is important in HFD-induced renal fibrosis development during aging.
与年龄或高脂饮食（HFD）相关的肾脏结构变化通常与肾功能下降有关。尽管高脂饮食在衰老过程中会对各个器官造成有害影响，但其对与年龄相关的肾纤维化的影响尚未得到研究。在本研究中，我们发现短期高脂饮食会通过导致老年Sprague-Dawley（SD）大鼠线粒体完整性丧失，从而显著诱导肾纤维化。为了评估短期摄入高脂饮食对与年龄相关的肾纤维化的影响，我们对年轻和老年SD大鼠给予高脂饮食15天。我们的结果表明，短期高脂饮食显著增加了老年大鼠的肾纤维化和炎症。此外，高脂饮食喂养的老年大鼠肾脏中的线粒体完整性以及脂肪酸氧化相关蛋白的表达均降低。此外，用油酸处理使NRK52E肾小管上皮细胞受到脂质应激后，线粒体氧化磷酸化相关蛋白的数量减少。我们的结果表明，短期高脂饮食会影响线粒体完整性并加剧炎症，从而导致肾纤维化，尤其是在老年大鼠中。我们得出结论，肾脏组织中的线粒体完整性在衰老过程中高脂饮食诱导的肾纤维化发展中很重要。
