Dietary L-arginine supplementation reduces fat mass in Zucker diabetic fatty rats
Dietary L-arginine supplementation reduces fat mass in Zucker diabetic fatty rats
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DOI：
10.1093/jn/135.4.714
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发表时间：
2005-04-01
影响因子：
4.2
通讯作者：
Wu, GY
中科院分区：
文献类型：
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作者：
Fu, WJJ;Haynes, TE;Wu, GY
这项研究的目的是检验这样的假设：膳食补充精氨酸（一氧化氮 (NO) 的生理前体）可减少 Zucker 糖尿病脂肪 (ZDF) 大鼠（一种遗传性肥胖的 II 型糖尿病动物模型）的脂肪量。 9周龄雄性ZDF大鼠采用Purina 5008饮食配对喂养，并接受含有精氨酸-HCl（1.51％）或丙氨酸（2.55％，等氮对照）的饮用水10周。精氨酸和NO的血清浓度。补充精氨酸的大鼠中，NO 的氧化产物分别比对照大鼠高 261% 和 70%。与对照大鼠相比，精氨酸治疗大鼠的体重在治疗开始后第 4、7 和 10 周分别降低了 6%、10% 和 16%。补充精氨酸可降低腹部（腹膜后）和附睾脂肪组织的重量（分别为 45% 和 25%），并降低血清中葡萄糖（25%）、甘油三酯（23%）、FFA（27%）、同型半胱氨酸（26%）、二甲基精氨酸（18-21%）和瘦素（32%）的浓度。精氨酸治疗增强了腹部和附睾脂肪组织中一氧化氮的产生（71-85%）、脂肪分解（22-24%）以及葡萄糖（34-36%）和辛酸（40-43%）的氧化。微阵列分析结果表明，补充精氨酸增加了脂肪组织中负责脂肪酸和葡萄糖氧化的关键基因的表达：NO合酶-1（145%）、血红素加氧酶-3（789%）、AMP激活蛋白激酶（123%）和过氧化物酶体增殖物激活受体γ共激活剂-1α（500%）。通过实时 RT-PCR 分析验证了这些基因的诱导。总之，精氨酸治疗可能提供一种潜在的新颖且有用的方法来增强患有 II 型糖尿病的肥胖受试者的 NO 合成并减少脂肪量。
This study was conducted to test the hypothesis that dietary supplementation of arginine, the physiologic precursor of nitric oxide (NO), reduces fat mass in the Zucker diabetic fatty (ZDF) rat, a genetically obese animal model of type-II diabetes mellitus. Male ZDF rats, 9 wk old, were pair-fed Purina 5008 diet and received drinking water containing arginine-HCl (1.51%) or alanine (2.55%, isonitrogenous control) for 10 wk. Serum concentrations of arginine and NO. (oxidation products of NO) were 261 and 70% higher, respectively, in arginine-supplemented rats than in control rats. The body weights of arginine-treated rats were 6, 10, and 16% lower at wk 4, 7, and 10 after the treatment initiation, respectively, compared with control rats. Arginine supplementation reduced the weight of abdominal (retroperitoneal) and epididymal adipose tissues (45 and 25%, respectively) as well as serum concentrations of glucose (25%), triglycerides (23%), FFA (27%), homocysteine (26%), dimethylarginines (18-21%), and leptin (32%). The arginine treatment enhanced NO production (71-85%), lipolysis (22-24%), and the oxidation of glucose (34-36%) and octanoate (40-43%) in abdominal and epididymal adipose tissues. Results of the microarray analysis indicated that arginine supplementation increased adipose tissue expression of key genes responsible for fatty acid and glucose oxidation: NO synthase-1 (145%), heme oxygenase-3 (789%), AMP-activated protein kinase (123%), and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (500%). The induction of these genes was verified by real-time RT-PCR analysis. In sum, arginine treatment may provide a potentially novel and useful means to enhance NO synthesis and reduce fat mass in obese subjects with type-II diabetes mellitus.