脂肪毒性:肥胖和耐力训练的悖论。

A P Russell
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引用次数: 73

摘要

细胞内甘油三酯(IMTG)积累的潜在脂毒性作用已被认为是胰岛素抵抗发展的主要组成部分。在肥胖和糖尿病患者中,imtg水平升高与胰岛素抵抗相关,但这种关系在耐力训练(ETr)受试者中不存在。这可能部分与肥胖/糖尿病患者与ETr受试者相比,参与脂肪酸运输和氧化的关键酶的基因表达和活性以及imtg过氧化物状态的差异有关。骨骼肌中脂肪和脂质稳态的破坏已被证明可以激活蛋白激酶C (PKC), PKC作用于几种下游信号通路,包括胰岛素和IKK /NFkappaB信号通路。此外,imtg过氧化的增加可能通过增加TNFalpha来降低胰岛素敏感性,TNFalpha可以增加细胞因子信号蛋白(SOCS)抑制因子的表达。激活PKC和TNFalpha/SOCS3时观察到的一个共同特征是抑制IRS-1的酪氨酸磷酸化,随后抑制其下游信号分子的激活。这些可能是胰岛素抵抗发展的重要参与者,了解它们在肥胖和ETr人群中的激活和表达应该有助于理解imtg如何以及为什么会产生脂肪毒性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Lipotoxicity: the obese and endurance-trained paradox.

The potential lipotoxic effect of intramyocellular triglyceride (IMTG) accumulation has been suggested to be a major component in the development of insulin resistance. Increased levels of IMTGs correlate with insulin resistance in both obese and diabetic patients, but this relationship does not exist in endurance trained (ETr) subjects. This may be, in part, related to differences in the gene expression and activities of key enzymes involved in fatty acid transport and oxidation as well as in the perodixation status of the IMTGs in obese/diabetic patients as compared with ETr subjects. Disruptions in fat and lipid homeostasis in skeletal muscle have been shown to activate protein kinase C (PKC), which acts on several downstream signalling pathways, including the insulin and the IkappaB kinase (IKK)/NFkappaB signalling pathways. Additionally, an increased peroxidation of IMTGs may reduce insulin sensitivity by increasing TNFalpha, which is known to increase the expression of suppressor of cytokine signalling proteins (SOCS). A common characteristic observed when activating both PKC and TNFalpha/SOCS3 is the inhibition of tyrosine phosphorylation of IRS-1 and subsequently an inhibition of its activation of downstream signalling molecules. These may be important players in the development of insulin resistance and understanding their activation and expression in both obese and ETr humans should assist in understanding how and why IMTGs become lipotoxic.

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