PPAR-alpha agonism improves whole body and muscle mitochondrial fat oxidation, but does not alter intracellular fat concentrations in burn trauma children in a randomized controlled trial.
PPAR-alpha agonism improves whole body and muscle mitochondrial fat oxidation, but does not alter intracellular fat concentrations in burn trauma children in a randomized controlled trial.
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DOI：
10.1186/1743-7075-4-9
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发表时间：
2007-04-23
影响因子：
4.5
通讯作者：
Wolfe RR
中科院分区：
文献类型：
--
作者：
Cree MG;Newcomer BR;Herndon DN;Qian T;Sun D;Morio B;Zwetsloot JJ;Dohm GL;Fram RY;Mlcak RP;Aarsland A;Wolfe RR
胰岛素抵抗通常与细胞内甘油三酯、二酰甘油水平升高和脂肪β氧化减少有关。目前尚不清楚创伤引起的急性胰岛素抵抗患者是否存在这种关系。对18例严重烧伤患儿进行了双盲安慰剂对照试验。比较了安慰剂或PPAR-α激动剂治疗前后的代谢研究，以评估全身棕榈酸酯氧化和胰岛素敏感性，肌肉活检线粒体棕榈酸酯氧化，二酰甘油，脂肪酰辅酶A和脂肪酰肉碱浓度，以及肌肉和肝脏甘油三酯的磁共振波谱。与安慰剂相比，PPAR-α激动剂治疗后胰岛素敏感性和基础全身棕榈酸酯氧化显著增加(分别为P=0.003和P=0.004)。经PPAR-α处理后，肌肉样本中线粒体棕榈酸酯氧化速率显著增加(P=0.002)。然而，肌肉甘油三酯、二酰甘油、脂肪酰辅酶A、脂肪酰肉碱和肝脏甘油三酯的浓度并没有随着这两种处理的变化而改变。PPAR-θ治疗后，高胰岛素血症时PKC-α活性显著降低。在急性创伤中，PPAR-α激动剂治疗增加了棕榈酸酯氧化和降低了PKC活性，同时降低了胰岛素敏感性，然而，这些反应之间的直接联系不能归因于细胞内脂质浓度的变化。
Insulin resistance is often associated with increased levels of intracellular triglycerides, diacylglycerol and decreased fat β-oxidation. It was unknown if this relationship was present in patients with acute insulin resistance induced by trauma. A double blind placebo controlled trial was conducted in 18 children with severe burn injury. Metabolic studies to assess whole body palmitate oxidation and insulin sensitivity, muscle biopsies for mitochondrial palmitate oxidation, diacylglycerol, fatty acyl Co-A and fatty acyl carnitine concentrations, and magnetic resonance spectroscopy for muscle and liver triglycerides were compared before and after two weeks of placebo or PPAR-α agonist treatment. Insulin sensitivity and basal whole body palmitate oxidation as measured with an isotope tracer increased significantly (P = 0.003 and P = 0.004, respectively) after PPAR-α agonist treatment compared to placebo. Mitochondrial palmitate oxidation rates in muscle samples increased significantly after PPAR-α treatment (P = 0.002). However, the concentrations of muscle triglyceride, diacylglycerol, fatty acyl CoA, fatty acyl carnitine, and liver triglycerides did not change with either treatment. PKC-θ activation during hyper-insulinemia decreased significantly following PPAR-α treatment. PPAR-α agonist treatment increases palmitate oxidation and decreases PKC activity along with reduced insulin sensitivity in acute trauma, However, a direct link between these responses cannot be attributed to alterations in intracellular lipid concentrations.
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影响因子：
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作者：
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