High fat feeding and dietary l-arginine supplementation differentially regulate gene expression in rat white adipose tissue
High fat feeding and dietary l-arginine supplementation differentially regulate gene expression in rat white adipose tissue
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DOI：
10.1007/s00726-009-0246-7
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发表时间：
2009-05-01
期刊：
影响因子：
3.5
通讯作者：
Wu, Guoyao
中科院分区：
文献类型：
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作者：
Jobgen, Wenjuan;Fu, Wenjiang J.;Wu, Guoyao
补充L-精氨酸（Arg）可减少饮食诱导的肥胖大鼠的白脂肪增加，但其潜在机制尚不清楚。本研究验证了精氨酸治疗影响脂肪组织中脂质代谢相关基因表达的假设。将4周龄的雄性Sprague-Dawley大鼠喂食低脂肪（LF）或高脂肪（HF）饮食15周。此后，瘦或肥胖大鼠继续喂食各自相同的饮食，并接受含有1. 51% Arg-HCl或2.55%l-丙氨酸的饮用水（等氮对照）。在补充Arg 12周后，将大鼠安乐死以获得腹膜后脂肪组织，用于通过微阵列分析基因表达的总体变化。RT-PCR分析证实了上述结果。HF喂养降低了脂肪生成酶、AMP激活蛋白激酶、葡萄糖转运蛋白、血红素加氧酶3、谷胱甘肽合成酶、超氧化物歧化酶3、过氧化物氧还蛋白5、谷胱甘肽过氧化物酶3和应激诱导蛋白的mRNA水平，同时增加了羧肽酶A、过氧化物酶体增殖物激活受体（PPAR）-α、半胱天冬酶2、小窝蛋白3和甘油二酯激酶的表达。与此相反，精氨酸补充减少mRNA水平的脂肪酸结合蛋白1，糖原，磷酸蛋白1B，半胱天冬酶1和2，和肝脂肪酶，但增加表达的过氧化物酶体增殖物激活受体γ，血红素加氧酶3，谷胱甘肽合成酶，胰岛素样生长因子II，鞘氨醇-1-磷酸受体，和应激诱导蛋白。生化分析显示HF喂养大鼠的白色脂肪组织中存在氧化应激，补充精氨酸可预防氧化应激。总的来说，这些结果表明，HF饮食和精氨酸补充差异调节基因表达，影响能量底物氧化，氧化还原状态，脂肪增生，脂肪组织中的脂肪细胞分化。我们的研究结果提供了一个分子机制，以解释一个有益的影响，精氨酸改善饮食诱导的肥胖在哺乳动物。
Dietary l-arginine (Arg) supplementation reduces white-fat gain in diet-induced obese rats but the underlying mechanisms are unknown. This study tested the hypothesis that Arg treatment affects expression of genes related to lipid metabolism in adipose tissue. Four-week-old male Sprague-Dawley rats were fed a low-fat (LF) or high-fat (HF) diet for 15 weeks. Thereafter, lean or obese rats continued to be fed their same respective diets and received drinking water containing 1.51% Arg-HCl or 2.55% l-alanine (isonitrogenous control). After 12 weeks of Arg supplementation, rats were euthanized to obtain retroperitoneal adipose tissue for analyzing global changes in gene expression by microarray. The results were confirmed by RT-PCR analysis. HF feeding decreased mRNA levels for lipogenic enzymes, AMP-activated protein kinase, glucose transporters, heme oxygenase 3, glutathione synthetase, superoxide dismutase 3, peroxiredoxin 5, glutathione peroxidase 3, and stress-induced protein, while increasing expression of carboxypeptidase-A, peroxisome proliferator activated receptor (PPAR)-alpha, caspase 2, caveolin 3, and diacylglycerol kinase. In contrast, Arg supplementation reduced mRNA levels for fatty acid binding protein 1, glycogenin, protein phosphates 1B, caspases 1 and 2, and hepatic lipase, but increased expression of PPAR gamma, heme oxygenase 3, glutathione synthetase, insulin-like growth factor II, sphingosine-1-phosphate receptor, and stress-induced protein. Biochemical analysis revealed oxidative stress in white adipose tissue of HF-fed rats, which was prevented by Arg supplementation. Collectively, these results indicate that HF diet and Arg supplementation differentially regulate gene expression to affect energy-substrate oxidation, redox state, fat accretion, and adipocyte differentiation in adipose tissue. Our findings provide a molecular mechanism to explain a beneficial effect of Arg on ameliorating diet-induced obesity in mammals.