Division of Nephrology and Hypertension, University of California, Irvine, Orange, CA 92868, USA.
J Nutr Biochem. 2010 Oct;21(10):999-1007. doi: 10.1016/j.jnutbio.2009.08.006. Epub 2009 Dec 1.
Chronic renal failure (CRF) is associated with malnutrition and renal tissue accumulation of lipids, which can contribute to progression of renal disease. This study was designed to explore the effect of a high-calorie diet on pathways involved in lipid metabolism in the remnant kidney of rats with CRF. 5/6 nephrectomized rats were randomized to receive a regular diet (3.0 kcal/g) or a high-calorie diet (4.5 kcal/g) for 12 weeks. Renal lipid contents and abundance of molecules involved in cholesterol and fatty acid metabolism were studied. The CRF group consuming a regular diet exhibited growth retardation; azotemia; proteinuria; glomerulosclerosis; tubulointerstitial injury; heavy lipid accumulation in the remnant kidney; up-regulation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), ATP-binding cassette transporter-1 (ABCA1), liver X receptor (LXR) α/β, carbohydrate-responsive element binding protein (ChREBP) and acyl-CoA carboxylase (ACC); and down-regulation of peroxisome proliferator-activated receptor-α (PPAR-α), carnitine palmitoyltransferase-1 (CPT1) and liver-type fatty acid binding protein (L-FABP). The high-calorie diet restored growth; reduced the severity of tubulointerstitial injury, proteinuria and azotemia; partially lowered renal tissue lipid contents; attenuated the up-regulation of mediators of lipid influx (LOX-1), lipid efflux (LXR-α/β and ABCA1) and fatty acid biosynthesis (ChREBP and ACC); and reversed the down-regulation of factors involved in fatty acid oxidation (PPAR-α, CPT1 and L-FABP). In conclusion, a high-calorie diet restores growth, improves renal function and structure, and lowers lipid burden in the remnant kidney. The latter is associated with and most likely due to reduction in lipid influx and enhancement of fatty acid oxidation.
慢性肾衰竭（CRF）与营养不良和肾脏组织脂质积累有关，这可能导致肾脏疾病的进展。本研究旨在探讨高热量饮食对 CRF 大鼠残肾脂质代谢途径的影响。5/6 肾切除术大鼠随机分为接受常规饮食（3.0 千卡/克）或高热量饮食（4.5 千卡/克）12 周。研究了肾脏脂质含量和胆固醇及脂肪酸代谢相关分子的丰度。接受常规饮食的 CRF 组表现为生长迟缓；氮质血症；蛋白尿；肾小球硬化；肾小管间质损伤；残肾脂质大量堆积；凝集素样氧化低密度脂蛋白受体-1（LOX-1）、三磷酸腺苷结合盒转运体 A1（ABCA1）、肝 X 受体（LXR）α/β、碳水化合物反应元件结合蛋白（ChREBP）和酰基辅酶 A 羧化酶（ACC）上调；过氧化物酶体增殖物激活受体-α（PPAR-α）、肉碱棕榈酰转移酶 1（CPT1）和肝型脂肪酸结合蛋白（L-FABP）下调。高热量饮食恢复了生长；降低了肾小管间质损伤、蛋白尿和氮质血症的严重程度；部分降低了肾脏组织脂质含量；减轻了脂质摄取（LOX-1）、脂质外排（LXR-α/β 和 ABCA1）和脂肪酸合成（ChREBP 和 ACC）介质的上调；并逆转了脂肪酸氧化相关因子（PPAR-α、CPT1 和 L-FABP）的下调。总之，高热量饮食可恢复生长，改善肾功能和结构，并降低残肾脂质负担。后者与并可能由于脂质摄取减少和脂肪酸氧化增强有关。
