cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids
cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids
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DOI：
10.1074/jbc.m707775200
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发表时间：
2008-03-14
影响因子：
4.8
通讯作者：
Kristiansen, Karsten
中科院分区：
文献类型：
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作者：
Madsen, Lise;Pedersen, Lone Moller;Kristiansen, Karsten
n-6多不饱和脂肪酸（n-6 PUFAs）对脂肪形成和肥胖的影响存在争议。使用体外细胞培养模型，我们表明，n-6 PUFAs是促脂肪形成的条件下，与基线水平的cAMP，但抗脂肪形成时，cAMP的水平升高。n-6 PUFA的抗脂肪形成作用依赖于cAMP依赖性蛋白激酶介导的环氧合酶表达和活性的诱导。我们表明，n-6 PUFA与高碳水化合物饮食结合时是促脂肪形成的，但与高蛋白饮食结合时是非脂肪形成的。高蛋白饮食增加胰高血糖素/胰岛素比率，导致cAMP依赖性信号传导升高和环加氧酶介导的前列腺素合成诱导。喂食高蛋白饮食的小鼠的饲料效率明显低于喂食高碳水化合物饮食的小鼠。然而，耗氧量和表观产热量是相似的。高蛋白饮食的小鼠肝脏PGC-1 α（过氧化物酶体增殖物激活受体γ共激活因子1 α）和参与能量需求过程（如尿素合成和尿素生成）的基因表达增加。我们的结论是，cAMP信号是调节n-6 PUFAs的脂肪形成作用的关键，饮食诱导的cAMP水平的差异可以解释n-6 PUFAs增强或抵消脂肪形成和肥胖的能力。
The effect of n-6 polyunsaturated fatty acids ( n-6 PUFAs) on adipogenesis and obesity is controversial. Using in vitro cell culture models, we show that n-6 PUFAs was pro-adipogenic under conditions with base-line levels of cAMP, but anti-adipogenic when the levels of cAMP were elevated. The anti-adipogenic action of n-6 PUFAs was dependent on a cAMP-dependent protein kinase-mediated induction of cyclooxygenase expression and activity. We show that n-6 PUFAs were pro-adipogenic when combined with a high carbohydrate diet, but non-adipogenic when combined with a high protein diet in mice. The high protein diet increased the glucagon/ insulin ratio, leading to elevated cAMP-dependent signaling and induction of cyclooxygenase-mediated prostaglandin synthesis. Mice fed the high protein diet had a markedly lower feed efficiency than mice fed the high carbohydrate diet. Yet, oxygen consumption and apparent heat production were similar. Mice on a high protein diet had increased hepatic expression of PGC-1 alpha(peroxisome proliferator-activated receptor gamma coactivator 1 alpha) and genes involved in energy-demanding processes like urea synthesis and gluconeogenesis. We conclude that cAMP signaling is pivotal in regulating the adipogenic effect of n-6 PUFAs and that diet-induced differences in cAMP levels may explain the ability of n-6 PUFAs to either enhance or counteract adipogenesis and obesity.