Molecular mechanisms associated with leptin resistance: n-3 polyunsaturated fatty acids induce alterations in the tight junction of the brain
Molecular mechanisms associated with leptin resistance: n-3 polyunsaturated fatty acids induce alterations in the tight junction of the brain
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DOI：
10.1016/j.cmet.2005.04.004
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发表时间：
2005-05-01
期刊：
影响因子：
29
通讯作者：
Mori, M
中科院分区：
文献类型：
--
作者：
Oh-I, S;Shimizu, H;Mori, M
高脂饮食引起外周瘦素抵抗，饮食脂质组成影响对瘦素的敏感性。我们研究了n-3多不饱和脂肪酸（PUFA）在外周瘦素抵抗中的作用。膳食PUFAs（0.4%wt/wt）引起不敏感的外周，但不是inlracrebroventricularly管理瘦素。n-3 PUFA增加体重，与脑脊液中瘦素浓度的显著降低相关。膳食n-3 PUFA减少了内源性或外源性瘦素进入大脑的运输，与下丘脑occludin的表达增加有关，但不引起瘦素受体、瘦素信号相关蛋白或其他紧密连接蛋白表达的变化。连续脑室内输注靶向occludin mRNA的反义吗啉代寡核苷酸逆转n-3 PUFA诱导的对外周给药瘦素的不敏感性。我们的结论是，n-3多不饱和脂肪酸诱导外周瘦素抵抗通过增加下丘脑occludin的表达，减少细胞旁运输瘦素进入大脑。
High-fat diets cause peripheral leptin resistance, and dietary lipid composition affects sensitivity to leptin. We examined the role of n-3 polyunsaturated fatty acid (PUFA) in peripheral leptin resistance. Dietary PUFAs (0.4% wt/wt) caused insensitivity to peripherally but not inlracerebroventricularly administered leptin. n-3 PUFA increased body weight, associated with a significant reduction of leptin concentration in the cerebrospinal fluid. Dietary n-3 PUFA reduced transport of endogenous or exogenously administered leptin into the brain, associated with increased expression of hypothalamic occludin, but caused no change in expression of leptin receptors, proteins associated with leptin signaling or other tight junction proteins. Continuous intracerebroventricular infusion of an antisense morpholino oligonucleotide targeted to occludin mRNA reversed n-3 PUFA-induced insensitivity to peripherally administered leptin. We conclude that n-3 PUFA induces peripheral leptin resistance via an increase in the expression of hypothalamic occludin, reducing paracellular transport of leptin into the brain.