Arctigenin improves lipid metabolism by regulating AMP‐activated protein kinase and downstream signaling pathways

Abstract

Although it has been reported that arctigenin (ARG) can reduce the body weight and inhibit adipogenic differentiation by activating AMP-activated protein kinase (AMPK), the exact signals responsible for the ARG-mediated antiobesity mechanism through AMPK are not well understood. In this study, we investigated the potential improvement of AGR on lipid metabolism using a high-fat diet (HFD)-induced hyperlipidemia rats and 3T3-L1 mature adipocytes.The levels of AMPK and its downstream factors were examined by Western blot analysis and real-time fluorescent quantitative polymerase chain reaction. We observed that ARG lowered the HFD-induced body weight and the levels of serum lipid. Moreover, ARG clearly alleviated fat deposition in the liver and reduced epididymal fat accumulation. ARG also suppressed lipogenesis and lipolysis but promoted fatty acid β-oxidation in adipocytes. Most importantly, ARG increased the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) and upregulated the messenger RNA levels of downstream genes related to fatty acid β-oxidation, such as carnitine palmitoyltransferase 1 and acyl-CoA oxidase 1 but downregulated the expression of peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding transcription factor 1 (SREBP1c) and their targets, including lipogenesis-related genes such as CCAAT/enhancer-binding protein α, lipoprotein lipase, adipocyte protein 2, and fatty acid synthase (FAS), as well as lipolysis-related genes such as adipose triglyceride lipase and hormone-sensitive lipase. The activity of FAS was also decreased by ARG. We conclude that AMPK activation is important for the pharmacological effects of ARG. ARG may improve lipid metabolism by regulating the AMPK-ACC and AMPK-PPARγ/SREBP1c signaling pathways. K E Y W O R D S3T3-L1 adipocyte, AMP-activated protein kinase, arctigenin, fatty acid β-oxidation, HFD-induced hyperlipidemia SD rats, lipogenesis, lipolysis

Pterostilbene Inhibits Dyslipidemia-Induced Activation of Progenitor Adipose Gene Under High-Fat Diet and Radiation Stressor

“…34 The adipocytedifferentiation markers include PPARγ, PPARα, and C/EBPα, and the genes related to lipid metabolism include LPL, AP2, sterol regulatory element binding protein (SREBP) 1 c, FAS, acetyl-CoA carboxylate 1 (ACC1) and carnitine palmitoyltransferase 1B (CPT1B). 35 PPARγ and C/EBPα play synergistic roles in the activation and expression of genes that are activated in differentiation, and participate in a major adipocyte change. 36 In the present study, HFD rats exposed to irradiation showed a significant increase in body weight, accompanied by immense visceral adipose tissue.…”

Protective Effects of Huangqi Shengmai Yin on Type 1 Diabetes-Induced Cardiomyopathy by Improving Myocardial Lipid Metabolism

“…AMPK plays an important role in regulating the energy balance of cells. Activation of AMPK increases glucose uptake and FAO in metabolic diseases such as diabetes [ 45 , 46 ]. LKB1 is the main regulator of AMPK activation, and it can directly phosphorylate AMPK Thr-172 and activate its enzyme activity [ 47 ].…”

Methylophiopogonanone A, an Ophiopogon homoisoflavonoid, alleviates high-fat diet-induced hyperlipidemia: assessment of its potential mechanism

“…SREBP-1C is a crucial transcription factor, which binds to the endoplasmic reticulum to regulate triglyceride and fatty acid synthesis (26). Moreover, SREBP-1C is involved in de novo fatty acid synthesis via regulating the expression of ACC (27). Previous research indicated that decreasing the expression of SREBP-1C results in a decline of the incidence of dyslipidemia and simultaneously suppresses ACC expression in C57BL/6J mice (28).…”