The AMPK pathway in fatty liver disease

Abstract

Lipid metabolism disorders are the primary causes for the occurrence and progression of various liver diseases, including non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) caused by a high-fat diet and ethanol. AMPK signaling pathway plays an important role in ameliorating lipid metabolism disorders. Progressive research has clarified that AMPK signal axes are involved in the prevention and reduction of liver injury. Upregulation of AMK can alleviate FLD in mice induced by alcohol or insulin resistance, type 2 diabetes, and obesity, and most natural AMPK agonists can regulate lipid metabolism, inflammation, and oxidative stress in hepatocytes, consequently regulating FLD in mice. In NAFLD and AFLD, increasing the activity of AMPK can inhibit the synthesis of fatty acids and cholesterol by down-regulating the expression of adipogenesis gene (FAS, SREBP-1c, ACC and HMGCR); Simultaneously, by increasing the expression of fatty acid oxidation and lipid decomposition genes (CPT1, PGC1, and HSL, ATGL) involved in fatty acid oxidation and lipid decomposition, the body’s natural lipid balance can be maintained. At present, some AMPK activators are thought to be beneficial during therapeutic treatment. Therefore, activation of AMPK signaling pathway is a potential therapeutic target for disorders of the liver. We summarized the most recent research on the role of the AMPK pathway in FLD in this review. Simultaneously, we performed a detailed description of each signaling axis of the AMPK pathway, as well as a discussion of its mechanism of action and therapeutic significance.

Exercise alleviates diabetic complications by inhibiting oxidative stress-mediated signaling cascade and mitochondrial metabolic stress in GK diabetic rat tissues

“…Besides being a regulatory factor for energy status and glucose metabolism, it also plays a crucial role in regulating lipid metabolism, oxidative stress, and inflammatory responses ( Green et al, 2022 ). Fang et al have shown that these mitigative effects are achieved by activation of the Nrf2/keap1 pathway and inhibition of the NFκB pathway ( Fang et al, 2022 ). Activation of AMPK and SIRT-1 has been shown to regulate hexokinase activity along with the regulation of glycolytic and mitochondrial energy metabolism ( Cantó et al, 2009 ; Ren et al, 2022 ).…”

Activation of AMPK Entails the Protective Effect of Royal Jelly against High-Fat-Diet-Induced Hyperglycemia, Hyperlipidemia, and Non-Alcoholic Fatty Liver Disease in Rats

“…The ability of AMPK to treat NAFLD has been established in numerous animal and preclinical studies. It has been shown that the levels of AMPK activation are substantially decreased in animals and patients with NAFLD, whereas the activation of AMPK by genetic manipulation, exercise, activators (e.g., A-769662, EX229/991, MT47-100), and mitochondria inhibitors (e.g., metformin) showed protective effects [ 12 , 13 , 14 , 15 , 16 , 17 ]. Researchers have demonstrated that the protection afforded by AMPK is related to its ability to act using different mechanisms, including improving peripheral insulin sensitivity; suppressing de novo lipogenesis and lipogenic genes (e.g., sterol regulatory element-binding protein 1 (SREBP-1c) and acetyl-CoA carboxylase (ACC-1)); and stimulating adipose tissue, liver fatty acid oxidation, and mitochondria integrity/function [ 13 ].…”

Programmed cell death and lipid metabolism of macrophages in NAFLD

“…Currently, studies on HIF-1α and AMPK regulation of lipid metabolism in NAFLD are mainly carried out in hepatocytes ( 89 , 90 ). The mechanisms by which lipid metabolism reprogramming in macrophages regulates autophagy are still poorly understood.…”