Functional and structural changes in the kidney in the early stages of obesity
Functional and structural changes in the kidney in the early stages of obesity
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DOI：
10.1681/asn.v1261211
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发表时间：
2001-06-01
影响因子：
13.6
通讯作者：
Hall, JE
中科院分区：
文献类型：
--
作者：
Henegar, JR;Bigler, SA;Hall, JE
本研究的目的是检查由高脂肪饮食引起的肥胖早期肾脏的组织学和功能变化。瘦狗（n = 8）饲喂标准犬舍口粮，肥胖狗（n = 8）饲喂标准犬舍口粮加煮熟的牛油，每天饲喂7 - 9周或24周。与瘦狗的平均值相比，肥胖狗的体重增加58 +/- 5%，肾脏重量增加31 +/- 7%。肥胖狗的血浆肾素活性和胰岛素浓度都是瘦狗的2.3倍。与瘦狗相比，肥胖与平均动脉压升高12 +/- 3 mmHg、GFR升高38 +/- 6%和肾血浆流量升高61 +/- 7%相关。高脂肪饲粮犬肾小球鲍曼间隙面积（+41 +/- 7%）明显大于瘦肉犬，主要原因是鲍曼囊扩张（+22 +/- 7%）。与瘦狗相比，肥胖狗的肾小球系膜基质增加，肾小球和肾小管基底膜增厚，每个肾小球的分裂细胞（增殖细胞核抗原染色）数量增加了36 +/- 8%。通过半定量免疫组织化学分析估计，高脂肪饮食也有肾小球转化生长因子- β 1表达升高的趋势。因此，高脂肪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、肾小球高滤过和肾脏结构改变，这些可能是与长期肥胖相关的更严重肾小球损伤的前兆。
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.