Triglycerides cross the blood-brain barrier and induce central leptin and insulin receptor resistance.
Triglycerides cross the blood-brain barrier and induce central leptin and insulin receptor resistance.
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DOI：
10.1038/ijo.2017.231
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Craft S
中科院分区：
文献类型：
--
作者：
Banks WA;Farr SA;Salameh TS;Niehoff ML;Rhea EM;Morley JE;Hanson AJ;Hansen KM;Craft S
大脑中瘦素和胰岛素受体的抵抗与进食增加、肥胖和认知障碍有关。中枢阻力的致病因素尚不清楚，但可能来自血液。在这里，我们假设是否高脂血症，代谢综合征的主要血脂异常，可能是中枢瘦素和胰岛素抵抗的基础。我们使用放射性标记的甘油三酯来测量血脑屏障（BBB）的渗透，蛋白质印迹来测量受体激活，喂养和认知测试来评估行为终点。确定人CSF含有甘油三酯，这一发现以前尚不清楚。放射性甘油三酯三油酸甘油酯很容易穿过BBB和中央给药的三油酸甘油酯和外周给药的脂质诱导体内瘦素和/或下丘脑受体的胰岛素抵抗。中枢三油酸甘油酯阻断了中枢给予的瘦素的饱腹感效应。吉非罗齐降低血清甘油三酯可改善学习和记忆，与甘油三酯水平成反比。甘油三酯快速穿过血脑屏障，在人脑脊液中发现，并诱导中枢瘦素和胰岛素受体抵抗，降低饱腹感和认知能力。
Resistance at the brain receptors for leptin and insulin has been associated with increased feeding, obesity and cognitive impairments. The causal agent for central resistance is unknown but could be derived from the blood. Here we postulate whether hypertriglyceridemia, the major dyslipidemia of the metabolic syndrome, could underlie central leptin and insulin resistance. We used radioactively labeled triglycerides to measure blood–brain barrier (BBB) penetration, western blots to measure receptor activation, and feeding and cognitive tests to assess behavioral endpoints. Human CSF was determined to contain triglycerides, a finding previously unclear. The radioactive triglyceride triolein readily crossed the BBB and centrally administered triolein and peripherally administered lipids induced in vivo leptin and/or insulin resistance at hypothalamic receptors. Central triolein blocked the satiety effect of centrally administered leptin. Decreasing serum triglycerides with gemfibrozil improved both learning and memory inversely proportionate to triglyceride levels. Triglycerides cross the blood–brain barrier rapidly, are found in human cerebrospinal fluid, and induce central leptin and insulin receptor resistance, decreasing satiety and cognition.
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影响因子：
--
作者：
Craft, Suzanne;Baker, Laura D.;Montine, Thomas J.;Minoshima, Satoshi;Watson, G. Stennis;Claxton, Amy;Arbuckle, Matthew;Callaghan, Maureen;Tsai, Elaine;Plymate, Stephen R.;Green, Pattie S.;Leverenz, James;Cross, Donna;Gerton, Brooke
通讯作者：
Gerton, Brooke
影响因子：
3.7
作者：
Benedict, C;Hallschmid, M;Kern, W
通讯作者：
Kern, W
影响因子：
15.9
作者：
Sinha, MK;Opentanova, I;Caro, JF
通讯作者：
Caro, JF
影响因子：
13.5
作者：
Banks, William A.;Owen, Joshua B.;Erickson, Michelle A.
通讯作者：
Erickson, Michelle A.
影响因子：
3
作者：
Oomura, Y.;Hori, N.;Sasaki, K.
通讯作者：
Sasaki, K.