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

• Published in: Journal of cellular biochemistry Vol. 120; no. 8; pp. 13275 - 13288
• Main Authors: Song, Yuzhou, Li, Xiao, Liu, Yunyun, Hu, Yingjie, Yang, Ruiyi
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-08-2019
• Subjects: 3T3‐L1 adipocyte; Adipocytes; AMP; AMP‐activated protein kinase; arctigenin; Body weight; Carnitine; Carnitine palmitoyltransferase; Fat metabolism; fatty acid β‐oxidation; Fatty acids; Fatty-acid synthase; Fluorescence; Genes; HFD‐induced hyperlipidemia SD rats; High fat diet; Hyperlipidemia; Kinases; Lipase; Lipid metabolism; Lipids; Lipogenesis; Lipolysis; Lipoprotein lipase; Metabolism; mRNA; Oxidation; Palmitoyltransferase; Pharmacology; Phosphorylation; Polymerase chain reaction; Protein kinase; Protein turnover; Proteins; Regulatory sequences; Signal transduction; Signaling; HFD-induced hyperlipidemia SD rats; arctigenin; fatty acid β-oxidation; lipogenesis; AMP-activated protein kinase; lipolysis; 3T3-L1 adipocyte
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.28602

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.
Lipid metabolism disorder is one of the major pathological mechanisms of obesity, cardiovascular disease, and type 2 diabetes mellitus. Here we discovered that arctigenin (ARG; a major lignan constituent of Arctium lappa Linné) exhibited an ideal effect on lipid homeostasis in vitro and vivo. In this study, ARG had a stronger lowering effect on body weight gain, plasma lipid levels, and hepatic steatosis in high‐fat‐diet‐induced hyperlipidemia Sprague‐Dawley rats. In 3T3‐L1 adipocytes, ARG also played an effective role in inhibiting lipogenesis and lipolysis, while increasing fatty acid oxidation and glucose uptake by regulating AMP‐activated protein kinase and the downstream signaling pathway.