Dose-dependent lipid accumulation was induced by glucose in HepG2 cells. GlcN also exerted a promotory effect on lipid accumulation in HepG2 cells under normal glucose conditions (NG, 5 mM) and liver of normal fed zebrafish larvae. High glucose (HG, 25 mM)-induced lipid accumulation was suppressed by l-glutamine-d-fructose 6-phosphate amidotransferase inhibitors. ER stress inhibitors did not suppress HG or GlcN-mediated lipid accumulation. HG and GlcN stimulated protein expression, DNA binding and O-GlcNAcylation of carbohydrate-responsive element-binding protein (ChREBP). Furthermore, both HG and GlcN increased nuclear sterol regulatory element-binding protein-1 (SREBP-1) levels in HepG2 cells. In contrast to its stimulatory effect under NG, GlcN suppressed lipid accumulation in HepG2 cells under HG conditions. Similarly, GlcN suppressed lipid accumulation in livers of overfed zebrafish. In addition, GlcN activity on DNA binding and O-GlcNAcylation of ChREBP was stimulatory under NG and inhibitory under HG conditions. Moreover, GlcN enhanced ChREBP, SREBP-1c, ACC, FAS, L-PK and SCD-1 mRNA expression under NG but inhibited HG-induced upregulation in HepG2 cells. The O-GlcNAc transferase inhibitor, alloxan, reduced lipid accumulation by HG or GlcN while the O-GlcNAcase inhibitor, PUGNAc, enhanced lipid accumulation in HepG2 cells and liver of zebrafish larvae. GlcN-induced lipid accumulation was inhibited by the AMPK activator, AICAR. Phosphorylation of AMPK (p-AMPK) was suppressed by GlcN under NG while increased by GlcN under HG. PUGNAc downregulated p-AMPK while alloxan restored GlcN- or HG-induced p-AMPK inhibition. Our results collectively suggest that GlcN regulates lipogenesis by sensing the glucose or energy states of normal and excess fuel through AMPK modulation.

葡萄糖在HepG2细胞中诱导了剂量依赖性脂质蓄积。GlcN还对正常摄食的斑马鱼幼虫在正常葡萄糖条件下（NG，5 mM）和肝中HepG2细胞中的脂质蓄积起促进作用。高葡萄糖（HG，25毫摩尔）诱导的脂质蓄积是由抑制升-glutamine- d -fructose -6-磷酸酰胺转移酶抑制剂。ER应激抑制剂不能抑制HG或GlcN介导的脂质蓄积。HG和GlcN刺激蛋白表达，DNA结合和O-碳水化合物反应性元件结合蛋白（ChREBP）的-GlcNAcylation。此外，HG和GlcN均可增加HepG2细胞中的核固醇调节元件结合蛋白1（SREBP-1）水平。与其在NG下的刺激作用相反，GlcN在HG条件下抑制了HepG2细胞中的脂质蓄积。同样，GlcN抑制了过量喂养的斑马鱼肝脏中的脂质蓄积。另外，GlcN对ChREBP的DNA结合和O- GlcNAcy的活性在NG下是刺激性的，而在HG条件下是抑制性的。此外，GlcN增强NG下ChREBP，SREBP-1c，ACC，FAS，L-PK和SCD-1 mRNA表达，但抑制HG诱导的HepG2细胞上调。所述Ô -GlcNAc转移酶抑制剂，由HG或葡萄糖胺，而四氧嘧啶，降低脂质积累ö-GlcNAcase抑制剂PUGNAc增强了斑马鱼幼虫HepG2细胞和肝脏中脂质的积累。GlcN诱导的脂质蓄积被AMPK激活剂AICAR抑制。在NG下，GlcN抑制了AMPK的磷酸化（p-AMPK），而在HG下，GlcN抑制了AMPK的磷酸化。PUGNAc下调p-AMPK，而四氧嘧啶恢复GlcN-或HG诱导的p-AMPK抑制。我们的研究结果共同表明，GlcN通过AMPK调制检测正常和过量燃料的葡萄糖或能量状态来调节脂肪生成。