肝脂生成的表观遗传调控：在肝脂肪变性和糖尿病中的作用。
Epigenetic Regulation of Hepatic Lipogenesis: Role in Hepatosteatosis and Diabetes.
机构信息
Nutritional Science and Toxicology, University of California, Berkeley, Berkeley, CA.
Nutritional Science and Toxicology, University of California, Berkeley, Berkeley, CA
出版信息
Diabetes. 2020 Apr;69(4):525-531. doi: 10.2337/dbi18-0032.
Abstract
Hepatosteatosis, which is frequently associated with development of metabolic syndrome and insulin resistance, manifests when triglyceride (TG) input in the liver is greater than TG output, resulting in the excess accumulation of TG. Dysregulation of lipogenesis therefore has the potential to increase lipid accumulation in the liver, leading to insulin resistance and type 2 diabetes. Recently, efforts have been made to examine the epigenetic regulation of metabolism by histone-modifying enzymes that alter chromatin accessibility for activation or repression of transcription. For regulation of lipogenic gene transcription, various known lipogenic transcription factors, such as USF1, ChREBP, and LXR, interact with and recruit specific histone modifiers, directing specificity toward lipogenesis. Alteration or impairment of the functions of these histone modifiers can lead to dysregulation of lipogenesis and thus hepatosteatosis leading to insulin resistance and type 2 diabetes.
摘要
肝脂肪变性常与代谢综合征和胰岛素抵抗的发展相关，当肝脏中甘油三酯（TG）的输入大于 TG 的输出时，就会出现肝内 TG 的过度积累。因此，脂生成的失调有可能导致肝脏脂质的积累增加，从而导致胰岛素抵抗和 2 型糖尿病。最近，人们努力研究组蛋白修饰酶对代谢的表观遗传调控，这些酶改变染色质的可及性，以激活或抑制转录。对于脂生成基因转录的调节，各种已知的脂生成转录因子，如 USF1、ChREBP 和 LXR，相互作用并募集特定的组蛋白修饰酶，将特异性导向脂生成。这些组蛋白修饰酶的功能改变或损害可导致脂生成失调，从而导致肝脂肪变性，导致胰岛素抵抗和 2 型糖尿病。
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