Loss of Muscle Carnitine Palmitoyltransferase 2 Prevents Diet-Induced Obesity and Insulin Resistance despite Long-Chain Acylcarnitine Accumulation.
Loss of Muscle Carnitine Palmitoyltransferase 2 Prevents Diet-Induced Obesity and Insulin Resistance despite Long-Chain Acylcarnitine Accumulation.
复制标题
尽管长链链链球菌积累，但肌肉肉碱棕榈转移酶2仍能阻止饮食诱导的肥胖和胰岛素抵抗。
DOI：
10.1016/j.celrep.2020.108374
复制
发表时间：
2020-11-10
期刊：
影响因子：
8.8
通讯作者：
Ellis JM
中科院分区：
文献类型：
--
作者：
Pereyra AS;Rajan A;Ferreira CR;Ellis JM
为了评估酰基肉毒碱积累对肌肉胰岛素敏感性的影响，通过从骨骼肌（Cpt 2Sk −/−小鼠）中特异性地删除肉毒碱棕榈酰转移酶2（CPT 2）来产生肌肉酰基肉毒碱积累的模型。CPT 2是线粒体长链脂肪酸氧化的不可替代的酶，将基质酰基肉毒碱转化为酰基辅酶A。与对照组相比，Cpt 2Sk −/−肌肉不会积累合成代谢脂质，但会积累约22倍的长链酰基肉毒碱。高脂喂养的Cpt 2Sk −/−小鼠抵抗体重增加、肥胖、葡萄糖耐受不良、胰岛素抵抗和胰岛素诱导的Akt磷酸化损伤。Cpt 2Sk −/−小鼠的肥胖抵抗力可能归因于通过粪便的脂质排泄、GFD 15产生和能量消耗的增加。左旋肉碱补充干预降低酰基肉碱和改善胰岛素敏感性独立于肌肉线粒体脂肪酸氧化能力。肌肉CPT 2的损失导致高程度的长链酰基肉毒碱积累，同时防止饮食诱导的肥胖和胰岛素抵抗。Pereyra等人表明，肌肉线粒体长链脂肪酸氧化的损失导致肌肉和血浆中长链酰基肉毒碱的大量积累，而不会引起胰岛素抵抗。相反，不能通过β-氧化使脂肪酸流动可以防止饮食诱导的肥胖和胰岛素抵抗。
To assess the effects of acylcarnitine accumulation on muscle insulin sensitivity, a model of muscle acylcarnitine accumulation was generated by deleting carnitine palmitoyltransferase 2 (CPT2) specifically from skeletal muscle (Cpt2Sk−/− mice). CPT2 is an irreplaceable enzyme for mitochondrial long-chain fatty acid oxidation, converting matrix acylcarnitines to acyl-CoAs. Compared with controls, Cpt2Sk−/− muscles do not accumulate anabolic lipids but do accumulate ~22-fold more long-chain acylcarnitines. High-fat-fed Cpt2Sk−/− mice resist weight gain, adiposity, glucose intolerance, insulin resistance, and impairments in insulin-induced Akt phosphorylation. Obesity resistance of Cpt2Sk−/− mice could be attributed to increases in lipid excretion via feces, GFD15 production, and energy expenditure. L-carnitine supplement intervention lowers acylcarnitines and improves insulin sensitivity independent of muscle mitochondrial fatty acid oxidative capacity. The loss of muscle CPT2 results in a high degree of long-chain acylcarnitine accumulation, simultaneously protecting against diet-induced obesity and insulin resistance. Pereyra et al. show that loss of muscle mitochondrial long-chain fatty acid oxidation results in a large accumulation of long-chain acylcarnitines in muscle and plasma that do not cause insulin resistance. Rather, the inability to flux fatty acids through β-oxidation prevents diet-induced obesity and insulin resistance.
登录
查看更多内容
DOI：
10.1152/ajpendo.00602.2014
发表时间：
2015-06-01
影响因子：
5.1
作者：
McCoin, Colin S.;Knotts, Trina A.;Adams, Sean H.
通讯作者：
Adams, Sean H.
影响因子：
7.7
作者：
Keung W;Ussher JR;Jaswal JS;Raubenheimer M;Lam VH;Wagg CS;Lopaschuk GD
通讯作者：
Lopaschuk GD
影响因子：
6
作者：
Liepinsh, Edgars;Makrecka-Kuka, Marina;Dambrova, Maija
通讯作者：
Dambrova, Maija
影响因子：
9.3
作者：
Liepinsh, Edgars;Makrecka-Kuka, Marina;Dambrova, Maija
通讯作者：
Dambrova, Maija
影响因子：
7.7
作者：
Li LO;Grevengoed TJ;Paul DS;Ilkayeva O;Koves TR;Pascual F;Newgard CB;Muoio DM;Coleman RA
通讯作者：
Coleman RA