Lactate-induced lactylation in skeletal muscle is associated with insulin resistance in humans.
Lactate-induced lactylation in skeletal muscle is associated with insulin resistance in humans.
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乳酸诱导的骨骼肌乳酸化与人类胰岛素抵抗相关。
DOI：
10.3389/fphys.2022.951390
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发表时间：
2022
影响因子：
4
通讯作者：
Consitt, Leslie A.
中科院分区：
文献类型：
--
作者：
Maschari, Dominic;Saxena, Gunjan;Law, Timothy D.;Walsh, Erin;Campbell, Mason C.;Consitt, Leslie A.
循环乳酸盐升高与肥胖和胰岛素抵抗有关。本研究的目的是确定乳酸诱导的赖氨酸乳酸化（kla），一种翻译后修饰，是否存在于人类骨骼肌中并与胰岛素抵抗相关。对15名瘦型（体重指数：22.1 ± 0.5 kg/m2）和14名肥胖型（40.6 ± 1.4 kg/m2）成人进行肌肉活检和2小时口服葡萄糖耐量试验。与瘦女性相比，肥胖女性的骨骼肌乳酸化增加（19%，p < 0.05），并且在整个组中与胰岛素抵抗相关（r = 0.37，p < 0.05）。骨骼肌乳酸化水平与无氧代谢标志物（血浆乳酸和骨骼肌乳酸脱氢酶[LDH]，p < 0.05）显著相关，与氧化代谢标志物（骨骼肌细胞色素c氧化酶亚基4和复合物I [丙酮酸] OXPHOS能力，p < 0.05）呈负相关。用乳酸钠处理原代人骨骼肌细胞（HSkMC）24小时以类似的剂量依赖性方式增加蛋白质乳酸化和IRS-1丝氨酸636磷酸化（p < 0.05）。抑制糖酵解（用2-脱氧-d-葡萄糖）或LDH-A（用草氨酸钠或LDH-A siRNA）24小时减少HSkMC乳酸化，这导致培养基乳酸积累减少。本研究确定了人骨骼肌中存在乳酸衍生的翻译后修饰，并表明骨骼肌乳酸化可以为骨骼肌代谢（包括胰岛素抵抗）的调节提供额外的见解。
Elevated circulating lactate has been associated with obesity and insulin resistance. The aim of the current study was to determine if lactate-induced lysine lactylation (kla), a post-translational modification, was present in human skeletal muscle and related to insulin resistance. Fifteen lean (Body Mass Index: 22.1 ± 0.5 kg/m2) and fourteen obese (40.6 ± 1.4 kg/m2) adults underwent a muscle biopsy and 2-h oral glucose tolerance test. Skeletal muscle lactylation was increased in obese compared to lean females (19%, p < 0.05) and associated with insulin resistance (r = 0.37, p < 0.05) in the whole group. Skeletal muscle lactylation levels were significantly associated with markers of anaerobic metabolism (plasma lactate and skeletal muscle lactate dehydrogenase [LDH], p < 0.05) and negatively associated with markers of oxidative metabolism (skeletal muscle cytochrome c oxidase subunit 4 and Complex I [pyruvate] OXPHOS capacity, p < 0.05). Treatment of primary human skeletal muscle cells (HSkMC) with sodium lactate for 24 h increased protein lactylation and IRS-1 serine 636 phosphorylation in a similar dose-dependent manner (p < 0.05). Inhibition of glycolysis (with 2-deoxy-d-glucose) or LDH-A (with sodium oxamate or LDH-A siRNA) for 24 h reduced HSkMC lactylation which paralleled reductions in culture media lactate accumulation. This study identified the existence of a lactate-derived post-translational modification in human skeletal muscle and suggests skeletal muscle lactylation could provide additional insight into the regulation of skeletal muscle metabolism, including insulin resistance.
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DOI：
10.1249/mss.0b013e3181690760
发表时间：
2008-06-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Consitt, Leslie A.;Wideman, Laurie;Morrison, Ron F.
通讯作者：
Morrison, Ron F.
DOI：
10.1016/j.bbadis.2009.03.003
发表时间：
2009-06-01
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Kabra, Dhiraj G;Gupta, Jeena;Tikoo, Kulbhushan
通讯作者：
Tikoo, Kulbhushan
影响因子：
29
作者：
He, Ming;Chiang, Hou-Hsien;Chen, Danica
通讯作者：
Chen, Danica
影响因子：
7.7
作者：
Consitt LA;Bell JA;Koves TR;Muoio DM;Hulver MW;Haynie KR;Dohm GL;Houmard JA
通讯作者：
Houmard JA
影响因子：
7.7
作者：
Crawford SO;Hoogeveen RC;Brancati FL;Astor BC;Ballantyne CM;Schmidt MI;Young JH
通讯作者：
Young JH