Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu, India.
Department of Pathology, Karpaga Vinayaga Institute of Medical Sciences and Research Centre, Madhuranthagam, Tamil Nadu, India.
Tissue Cell. 2023 Jun;82:102054. doi: 10.1016/j.tice.2023.102054. Epub 2023 Mar 2.
Dysregulation of 5'-adenosine monophosphate-activated protein kinase (AMPK) occurs in metabolic disorders including non-alcoholic fatty liver disease (NAFLD) which makes it a molecular target for treatment. An AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) alleviates NAFLD in experimental rats, however the specific mechanism remains to be explored. We aimed to study the effect of AICAR on lipid levels, oxidant-antioxidant balance, AMPK and mTOR activation and FOXO3 gene expression in liver of mice model. Fatty liver was induced in two groups of C57BL/6 mice (groups 2 and 3) by providing a high fat high fructose diet (HFFD) for 10 weeks while groups 1 and 4 animals were fed normal pellet. For the last two weeks, groups 3 and 4 were administered AICAR (150 mg/kg bw/day, i.p.) while groups 1 and 2 were administered saline. AICAR decreased fatty liver, decreased glucose and insulin in circulation, prevented the accumulation of triglycerides and collagen and ameliorated oxidative stress in HFFD fed mice. At the molecular level, AICAR upregulated FOXO3 and p-AMPK expression and reduced p-mTOR expression. AMPK activation may involve FOXO3 in protection against NAFLD. The role of AMPK, mTOR and FOXO3 crosstalk in NAFLD needs to be characterised in future.
5'-腺苷单磷酸激活蛋白激酶（AMPK）的失调发生在代谢紊乱中，包括非酒精性脂肪性肝病（NAFLD），这使其成为治疗的分子靶点。AMPK 激活剂 5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷（AICAR）可缓解实验大鼠的 NAFLD，但具体机制仍需探讨。我们旨在研究 AICAR 对高脂高果糖饮食（HFFD）喂养 10 周的 C57BL/6 小鼠模型肝脏中脂质水平、氧化还原平衡、AMPK 和 mTOR 激活以及 FOXO3 基因表达的影响。两组 C57BL/6 小鼠（第 2 组和第 3 组）通过提供高脂肪高果糖饮食（HFFD）10 周来诱导脂肪肝，而第 1 组和第 4 组动物则喂食正常颗粒饲料。在最后两周，第 3 组和第 4 组给予 AICAR（150mg/kg bw/day，ip），而第 1 组和第 2 组给予生理盐水。AICAR 可减少脂肪肝、降低循环中的葡萄糖和胰岛素、防止甘油三酯和胶原的积累，并改善 HFFD 喂养小鼠的氧化应激。在分子水平上，AICAR 上调 FOXO3 和 p-AMPK 的表达，并降低 p-mTOR 的表达。AMPK 激活可能涉及 FOXO3 在保护 NAFLD 中的作用。未来需要进一步研究 AMPK、mTOR 和 FOXO3 串扰在 NAFLD 中的作用。
