Sterol regulatory element-binding protein-1c mediates increase of postprandial stearic acid, a potential target for improving insulin resistance, in hyperlipidemia.
Sterol regulatory element-binding protein-1c mediates increase of postprandial stearic acid, a potential target for improving insulin resistance, in hyperlipidemia.
复制标题
甾醇调节元件结合蛋白-1c 介导餐后硬脂酸的增加，这是改善高脂血症中胰岛素抵抗的潜在目标。
作者：
Chu X;Liu L;Na L;Lu H;Li S;Li Y;Sun C
血清游离脂肪酸（FFA）水平升高在胰岛素抵抗（IR）和糖尿病的发展中起重要作用。本研究探讨了人和小鼠高脂血症（HLP）餐后游离脂肪酸（FFA）的动态变化及其与胰岛素敏感性的关系。我们发现，血清硬脂酸（SA）是唯一的脂肪酸，是显着增加，在餐后状态。SA的升高是由于增加的胰岛素刺激的从头合成介导的固醇调节元件结合蛋白-1c（SREBP-1c）/乙酰辅酶A羧化酶/脂肪酸合成酶/延长的长链脂肪酸家族成员6（DLVL 6）和延长的棕榈酸（PA）由DLVL 6催化。小分子干扰RNA下调SREBP-1c或SREBP VL 6表达可降低HLP小鼠肝脏SA合成和血清SA水平，改善IR。然而，抑制SREBP-1c在改善IR方面比抑制PANVL 6更有效，这导致PA积累。总之，餐后SA增加是由胰岛素刺激的SREBP-1c通路和HLP中PA的延长引起的。减少餐后SA是改善IR的良好候选者，SREBP-1c可能是通过减少SA预防IR和糖尿病的更好靶点。
Elevated serum free fatty acids (FFAs) levels play an important role in the development of insulin resistance (IR) and diabetes. We investigated the dynamic changes and the underlying regulatory mechanism of postprandial FFA profile in hyperlipidemia (HLP) and their relation with insulin sensitivity in both humans and mice. We found that serum stearic acid (SA) is the only fatty acid that is increased dramatically in the postprandial state. The elevation of SA is due to increased insulin-stimulated de novo synthesis mediated by sterol regulatory element–binding protein-1c (SREBP-1c)/acetyl-CoA carboxylase/fatty acid synthase/elongation of long-chain fatty acid family member 6 (ELOVL6) and the elongation of palmitic acid (PA) catalyzed by ELOVL6. Downregulation of SREBP-1c or ELOVL6 by small interfering RNA can reduce SA synthesis in liver and serum SA level, followed by amelioration of IR in HLP mice. However, inhibition of SREBP-1c is more effective in improving IR than suppression of ELOVL6, which resulted in accumulation of PA. In summary, increased postprandial SA is caused by the insulin-stimulated SREBP-1c pathway and elongation of PA in HLP. Reduction of postprandial SA is a good candidate for improving IR, and SREBP-1c is potentially a better target to prevent IR and diabetes by decreasing SA.
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影响因子：
3.6
作者：
Nakajima, Takero;Tanaka, Naoki;Aoyama, Toshifumi
通讯作者：
Aoyama, Toshifumi
DOI：
10.1073/pnas.0401516101
发表时间：
2004-05-11
影响因子：
11.1
作者：
Iizuka, K;Bruick, RK;Uyeda, K
通讯作者：
Uyeda, K
影响因子：
6.1
作者：
Lu, Na;Li, Ying;Sun, Chang-Hao
通讯作者：
Sun, Chang-Hao
影响因子：
3.9
作者：
Melanson, Edward L.;Astrup, Arne;Donahoo, William T.
通讯作者：
Donahoo, William T.
影响因子：
9.8
作者：
Belfiore, F;Iannello, S;Cavaleri, A
通讯作者：
Cavaleri, A