Background

Low carnitine status may underlie the development of insulin resistance and metabolic inflexibility. Intravenous lipid infusion elevates plasma free fatty acid (FFA) concentration and is a model for simulating insulin resistance and metabolic inflexibility in healthy, insulin sensitive volunteers. Here, we hypothesized that co-infusion of L-carnitine may alleviate lipid-induced insulin resistance and metabolic inflexibility.

Methods

In a randomized crossover trial, eight young healthy volunteers underwent hyperinsulinemic-euglycemic clamps (40mU/m²/min) with simultaneous infusion of saline (CON), Intralipid (20%, 90mL/h) (LIPID), or Intralipid (20%, 90mL/h) combined with L-carnitine infusion (28mg/kg) (LIPID+CAR). Ten volunteers were randomized for the intervention arms (CON, LIPID and LIPID+CAR), but two dropped-out during the study. Therefore, eight volunteers participated in all three intervention arms and were included for analysis.

Results

L-carnitine infusion elevated plasma free carnitine availability and resulted in a more pronounced increase in plasma acetylcarnitine, short-, medium-, and long-chain acylcarnitines compared to lipid infusion, however no differences in skeletal muscle free carnitine or acetylcarnitine were found. Peripheral insulin sensitivity and metabolic flexibility were blunted upon lipid infusion compared to CON but L-carnitine infusion did not alleviate this.

Conclusion

Acute L-carnitine infusion could not alleviated lipid-induced insulin resistance and metabolic inflexibility and did not alter skeletal muscle carnitine availability. Possibly, lipid-induced insulin resistance may also have affected carnitine uptake and may have blunted the insulin-induced carnitine storage in muscle. Future studies are needed to investigate this.

中文翻译：

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左旋肉碱输注不能减轻脂质诱导的胰岛素抵抗和代谢僵硬

背景

肉碱水平低可能是胰岛素抵抗和代谢僵硬发展的基础。静脉内脂质输注可提高血浆游离脂肪酸（FFA）的浓度，是模拟健康，对胰岛素敏感的志愿者的胰岛素抵抗和代谢僵硬的模型。在这里，我们假设左旋肉碱的共同输注可以减轻脂质诱导的胰岛素抵抗和代谢僵硬。

方法

在一项随机交叉试验中，八名年轻的健康志愿者接受了高胰岛素-正常血糖钳夹（40mU / m ² / min），同时输注了盐水（CON），脂质内（20％，90mL / h）（LIPID）或脂质内（20％） ，90mL / h）结合左旋肉碱输注（28mg / kg）（LIPID + CAR）。十名志愿者被随机分为干预组（CON，LIPID和LIPID + CAR），但两名在研究期间退出。因此，八名志愿者参加了所有三个干预部门，并进行了分析。

结果

左旋肉碱输注提高了血浆游离肉碱的利用率，与脂质输注相比，血浆乙酰肉碱，短链，中链和长链酰基肉碱的增加更为明显，但是骨骼肌游离肉碱或乙酰肉碱没有差异。与CON相比，脂质输注后外周胰岛素敏感性和代谢柔韧性减弱，但左旋肉碱输注并不能缓解这种情况。

结论

急性左旋肉碱的输注不能减轻脂质诱导的胰岛素抵抗和新陈代谢的僵化，也不会改变骨骼肌肉碱的可利用性。可能是，脂质诱导的胰岛素抵抗也可能影响肉碱的摄取，并且可能使胰岛素诱导的肉碱在肌肉中的储存减弱。需要对此进行进一步的研究。