Ogborn Malcolm R, Nitschmann Evan, Bankovic-Calic Neda, Weiler Hope A, Fitzpatrick-Wong Shirley, Aukema Harold M
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada.
Kidney Int. 2003 Oct;64(4):1214-21. doi: 10.1046/j.1523-1755.2003.00215.x.
Conjugated linoleic acid (CLA) describes positional isomers of linoleic acid (LA). Experimental health benefits of CLA include amelioration of malignancy and inflammatory disease and reduction of adiposity. The Han:SPRD-cy rat model of polycystic kidney disease (PKD) features prominent renal interstitial inflammation and fibrosis that is amenable to dietary modification. We studied CLA supplementation in the modification of inflammatory outcomes in the Han:SPRD-cy rat.
Male offspring of Han:SPRD-cy heterozygotes were fed diets, using corn oil or corn oil with a CLA enriched oil (1% of diet by weight as CLA). After 8 weeks, measurements included renal function and morphometry, ex vivo release of renal prostaglandin E2 (PGE2), and renal and hepatic tissue fatty acid profiles.
Urine creatinine was significantly higher in PKD animals fed CLA (P = 0.004), but differences in serum creatinine and creatinine clearance did not quite reach significance in PKD animals. CLA feeding reduced interstitial inflammation (P < 0.001), fibrosis (P = 0.03), and renal PGE2 release (P = 0.02). Cystic change and oxidized low-density lipoprotein (LDL) staining did not change significantly. CLA feeding produced increased renal and hepatic CLA isomers. Hepatic, but not renal, LA proportion was reduced on the CLA diet. The renal proportion of the PGE2 precursor, arachidonic acid (AA), was not changed by diet, but hepatic AA proportion increased significantly with CLA feeding (P= 0.009).
CLA reduces renal production of PGE2, without reduced availability of the precursor fatty acid, AA. Short-term feeding of CLA to Han:SPRD-cy rats also has significant renal anti-inflammatory and antifibrotic effects. As inflammation and fibrosis are important components of the progression of chronic renal injury, CLA may be a useful agent in dietary amelioration of renal disease.
共轭亚油酸(CLA)是亚油酸(LA)的位置异构体。CLA对健康的实验性益处包括改善恶性肿瘤和炎症性疾病以及减少肥胖。多囊肾病(PKD)的Han:SPRD-cy大鼠模型具有明显的肾间质炎症和纤维化,可通过饮食调整来改善。我们研究了补充CLA对Han:SPRD-cy大鼠炎症结局的影响。
将Han:SPRD-cy杂合子的雄性后代喂食含玉米油或含CLA富集油(占饮食重量的1%作为CLA)的玉米油的饮食。8周后,测量指标包括肾功能和形态学、肾前列腺素E2(PGE2)的体外释放以及肾和肝组织脂肪酸谱。
喂食CLA的PKD动物尿肌酐显著更高(P = 0.004),但PKD动物血清肌酐和肌酐清除率的差异未完全达到显著水平。喂食CLA可减轻间质炎症(P < 0.001)、纤维化(P = 0.03)和肾PGE2释放(P = 0.02)。囊肿变化和氧化低密度脂蛋白(LDL)染色无显著变化。喂食CLA使肾和肝中的CLA异构体增加。CLA饮食使肝中LA比例降低,但肾中未降低。饮食未改变PGE2前体花生四烯酸(AA)的肾比例,但喂食CLA使肝中AA比例显著增加(P = 0.009)。
CLA可降低肾PGE2的产生,而不降低前体脂肪酸AA的可用性。对Han:SPRD-cy大鼠短期喂食CLA也具有显著的肾抗炎和抗纤维化作用。由于炎症和纤维化是慢性肾损伤进展的重要组成部分,CLA可能是饮食改善肾病的有用药物。