Henegar Jeffrey R, Bigler Steven A, Henegar Lisa K, Tyagi Suresh C, Hall John E
Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi.
Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi.
J Am Soc Nephrol. 2001 Jun;12(6):1211-1217. doi: 10.1681/ASN.V1261211.
The purpose of this study was to examine the histologic and functional changes that occur in the kidney in the early stages of obesity caused by a high-fat diet. Lean dogs (n = 8) were fed a standard kennel ration, and obese dogs (n = 8) were fed the standard kennel ration plus a supplement of cooked beef fat each day for 7 to 9 wk or 24 wk. Body weights were 58 +/- 5% greater and kidney weights were 31 +/- 7% greater in obese dogs, compared with the average values for lean dogs. Plasma renin activity and insulin concentrations were both 2.3-fold greater in obese dogs, compared with lean dogs. Obesity was associated with a mean arterial pressure increase of 12 +/- 3 mmHg, a 38 +/- 6% greater GFR, and a 61 +/- 7% higher renal plasma flow, compared with lean dogs. The glomerular Bowman's space area was significantly greater (+41 +/- 7%) in dogs fed the high-fat diet, compared with lean animals, mainly because of expansion of Bowman's capsule (+22 +/- 7%). There was also increased mesangial matrix and thickening of the glomerular and tubular basement membranes and the number of dividing cells (proliferating cell nuclear antigen-stained) per glomerulus was 36 +/- 8% greater in obese dogs, compared with lean dogs. There was also a trend for glomerular transforming growth factor-beta1 expression, as estimated by semiquantitative immunohistochemical analysis, to be elevated with the high-fat diet. Therefore, a high-fat diet caused increased arterial pressure, hyperinsulinemia, activation of the renin-angiotensin system, glomerular hyperfiltration, and structural changes in the kidney that may be the precursors of more severe glomerular injury associated with prolonged obesity.
本研究的目的是检查由高脂饮食导致的肥胖早期阶段肾脏中发生的组织学和功能变化。给8只瘦狗喂食标准犬舍日粮，给8只肥胖狗每天喂食标准犬舍日粮并添加熟牛肉脂肪，持续7至9周或24周。与瘦狗的平均值相比，肥胖狗的体重高58±5%，肾脏重量高31±7%。与瘦狗相比，肥胖狗的血浆肾素活性和胰岛素浓度均高出2.3倍。与瘦狗相比，肥胖与平均动脉压升高12±3 mmHg、肾小球滤过率（GFR）高38±6%以及肾血浆流量高61±7%有关。与瘦动物相比，喂食高脂饮食的狗的肾小球鲍曼氏间隙面积显著增大（+41±7%），主要是由于鲍曼氏囊扩张（+22±7%）。系膜基质也增加，肾小球和肾小管基底膜增厚，与瘦狗相比，肥胖狗每个肾小球中分裂细胞（增殖细胞核抗原染色）的数量多36±8%。通过半定量免疫组织化学分析估计，高脂饮食也有使肾小球转化生长因子-β1表达升高的趋势。因此，高脂饮食导致动脉压升高、高胰岛素血症、肾素-血管紧张素系统激活、肾小球高滤过以及肾脏结构变化，这些可能是与长期肥胖相关的更严重肾小球损伤的先兆。
