Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia.
Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
Am J Physiol Renal Physiol. 2020 Mar 1;318(3):F826-F834. doi: 10.1152/ajprenal.00444.2019. Epub 2020 Feb 10.
Excessive fructose intake causes metabolic syndrome and lipid accumulation in the kidney and leads to renal dysfunction and damage. Exercise (Ex) improves lipids regulation, but the mechanisms are unclarified in the kidney. In the present study, male Sprague-Dawley rats were allocated to groups fed with control or high-fructose (HFr) diet. Part of rats in each group underwent aerobic treadmill Ex for 12 wk. Drug treatment was performed as the fenofibrate gavage during the last 4 wk on HFr diet-fed rats. Renal function, histological changes, and expression of regulators involved in fatty acid (FA) metabolism were assessed. In CON diet-fed groups, Ex did not affect renal function or histology and significantly increased renal expression of FA β-oxidation regulators including acyl-CoA dehydrogenases (CADs), acyl-CoA oxidase, peroxisome proliferator-activated receptor (PPAR)-α, and PPAR-γ coactivator (PGC)-1α and lipogenic factors including acetyl-CoA carboxylase (ACCα), FA synthase (FAS), and sterol regulatory element-binding protein 1c. HFr caused albuminuria, lipid accumulation, and renal pathohistological changes, which were attenuated by Ex but not by fenofibrate. HFr decreased renal expression of medium- and short-chain CADs and PPAR-α and increased renal expression of ACCα, FAS, and sterol regulatory element-binding protein 1c. Ex increased expression of CADs, carnitine palmitoyltransferase type I, acyl-CoA oxidase, PPAR-α, and PGC-1α and decreased renal expression of ACCα and FAS in HFr diet-fed rats. The Ex-induced FA metabolism alteration was similar to that in the fenofibrate-treated group. In conclusion, the present study indicates that Ex enhanced renal FA metabolism, which might protect the kidney in lipid dysregulation diseases.
过量的果糖摄入会导致代谢综合征和肾脏脂质积累，导致肾功能障碍和损伤。运动（Ex）可以改善脂质调节，但在肾脏中的机制尚不清楚。在本研究中，雄性 Sprague-Dawley 大鼠被分配到对照组或高果糖（HFr）饮食组。每组部分大鼠进行 12 周的有氧跑步机 Ex。在 HFr 饮食喂养的大鼠的最后 4 周，进行了非诺贝特灌胃治疗。评估了肾功能、组织学变化和参与脂肪酸（FA）代谢的调节剂的表达。在 CON 饮食喂养组中，Ex 对肾功能或组织学没有影响，显著增加了 FA β-氧化调节剂的肾表达，包括酰基辅酶 A 脱氢酶（CADs）、酰基辅酶 A 氧化酶、过氧化物酶体增殖物激活受体（PPAR）-α 和 PPAR-γ 共激活因子（PGC）-1α 和脂生成因子，包括乙酰辅酶 A 羧化酶（ACCα）、脂肪酸合成酶（FAS）和固醇调节元件结合蛋白 1c。HFr 引起白蛋白尿、脂质积累和肾脏病理组织学变化，这些变化在 Ex 作用下减弱，但在非诺贝特作用下没有减弱。HFr 降低了中链和短链 CADs 和 PPAR-α 的肾表达，增加了 ACCα、FAS 和固醇调节元件结合蛋白 1c 的肾表达。Ex 增加了 CADs、肉碱棕榈酰转移酶 I、酰基辅酶 A 氧化酶、PPAR-α 和 PGC-1α 的表达，并降低了 HFr 饮食喂养大鼠肾 ACCα 和 FAS 的表达。Ex 诱导的 FA 代谢改变与非诺贝特治疗组相似。总之，本研究表明，Ex 增强了肾脏 FA 代谢，这可能在脂质失调疾病中保护肾脏。
