A low fish oil inhibits SREBP-1 proteolytic cascade, while a high-fish-oil feeding decreases SREBP-1 mRNA in mice liver: relationship to anti-obesity
A low fish oil inhibits SREBP-1 proteolytic cascade, while a high-fish-oil feeding decreases SREBP-1 mRNA in mice liver: relationship to anti-obesity
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DOI：
10.1194/jlr.m200289-jlr200
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发表时间：
2003-02-01
影响因子：
6.5
通讯作者：
Ezaki, O
中科院分区：
文献类型：
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作者：
Nakatani, T;Kim, HJ;Ezaki, O
与其他膳食油相比，喂食鱼油的啮齿动物表现出较少的肥胖，肝脏中甘油三酯合成减少，沿着成熟形式的固醇调节元件结合蛋白-1（SREBP-1）和过氧化物酶体增殖物激活受体CL（PPARalpha）的活化减少。鱼油对SREBP-1成熟蛋白表达的抑制作用可能与抑制SREBP-1蛋白水解级联反应或降低其mRNA表达有关。为了阐明其机制及其与减肥效果的关系，小鼠被喂食10 - 60%能量范围内的鱼油。鱼油喂养以剂量依赖性方式降低体重和脂肪量，与PPARalpha激活和SREBP-1 mRNA减少平行。然而，与0 en%鱼油喂养相比，10 en%鱼油喂养使成熟SREBP-1蛋白减少50%，伴随着脂肪生成基因的减少，而前体SREBP-1蛋白反而增加了1.3倍。这些数据表明，生理剂量的鱼油喂养通过抑制SREBP-1蛋白水解级联反应有效地降低了肝脏脂肪生成酶的表达，而在其药理剂量下观察到SREBP-1表达的显著降低，并且PPARalpha的激活而不是SREBP-1的降低可能与鱼油喂养的抗肥胖作用有关。
Rodents fed fish oil showed less obesity with a reduction of triglyceride synthesis in liver, relative to other dietary oils, along with a decrease of mature form of sterol regulatory element binding protein-1 (SREBP-1) and activation of peroxisome proliferator-activated receptor CL (PPARalpha). Decrease of mature SREBP-1 protein by fish oil feeding was due to either inhibition of SREBP-1 proteolytic cascade or to decrease of its mRNA. To clarify its mechanism and relation to antiobesity effect, mice were fed fish oil in a range from 10 to 60 energy percent (en%). Fish oil feeding decreased body weight and fat mass in a dose-dependent manner, in parallel with PPARalpha activation and a decrease of SREBP-1 mRNA. However, compared with 0 en% fish oil feeding, 10 en% fish oil feeding decreased mature SREBP-1 protein by 50% with concomitant decreases of lipogenic genes, while precursor SREBP-1 protein rather increased by 1.3-fold. These data suggest that physiological doses of fish oil feeding effectively decrease expression of liver lipogenic enzymes by inhibiting SREBP-1 proteolytic cascade, while substantial decrease of SREBP-1 expression is observed in its pharmacological doses, and that activation of PPARalpha rather than SREBP-1 decrease might be related to the antiobesity effect of fish oil feeding.