1. Academic Validation
  2. Amelioration of lipid accumulations and metabolism disorders in differentiation and development of 3T3-L1 adipocytes through mulberry leaf water extract

Amelioration of lipid accumulations and metabolism disorders in differentiation and development of 3T3-L1 adipocytes through mulberry leaf water extract

  • Phytomedicine. 2022 Jan 29;98:153959. doi: 10.1016/j.phymed.2022.153959.
Yan Du 1 Ding-Xiang Li 1 Dong-Yu Lu 2 Ran Zhang 1 Qiao-Qiao Zhong 1 Yan-Lin Zhao 2 Xiao-Xiao Zheng 3 Shuai Ji 4 Liang Wang 5 Dao-Quan Tang 6
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China.
  • 2 Department of Pharmacy, Suining People's Hospital Affiliated to Xuzhou Medical University, Suining 221202, China.
  • 3 Department of Pharmacy, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou 221002, China.
  • 4 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China; Department of Pharmaceutical Analysis, Xuzhou Medical University, Xuzhou 221204, China.
  • 5 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China; Department of Bioinformatics, School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou 2212004, China.
  • 6 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China; Department of Pharmacy, Suining People's Hospital Affiliated to Xuzhou Medical University, Suining 221202, China; Department of Pharmaceutical Analysis, Xuzhou Medical University, Xuzhou 221204, China. Electronic address: tangdq@xzhmu.edu.cn.
Abstract

Background: Obesity is a worldwide problem that resulted from the excessive fat accumulation in adipose tissue, leading to the impairment of individual health. Mulberry leaf is an important traditional Chinese medicine and has been used to alleviate obesity for a long term. However, its underlying molecular mechanisms have not been fully elucidated yet.

Purpose: In this study, we aimed to investigate the inhibition effects of mulberry leaf water extract (MLWE) on lipid accumulation during the process of differentiation of 3T3-L1 preadipocytes and development of mature adipocytes through the combination of Molecular Biology assays and metabolomic analysis.

Methods: The quality consistency and main chemical ingredients of MLWE were analyzed by high performance liquid chromatography and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), respectively. Oil red O staining was used to mirror lipid accumulation. Lipogenesis-, lipolysis- and inflammation-related genes were evaluated by Real-Time PCR and western blot, respectively. Untargeted metabolomics were performed by LC-MS/MS.

Results: Prepared method and quality of MLWE were stable and reliable. A total of 34 compounds were identified and 14 of them were undoubtedly confirmed. MLWE supplementation could dose-dependently inhibit the aggregation of lipid droplets, and the expressions of sterol regulatory element-binding protein (SREBP)-1c, Peroxisome Proliferator-activated Receptor (PPAR) γ, Acetyl-CoA Carboxylase (ACC), fatty acid synthase (FAS), tumor necrosis factor (TNF)-α and interleukin (IL)-6, and increase the expressions of adenosine monophosphate-activated protein kinase (AMPK), hormone-sensitive Lipase (HSL) and IL-10 in the differentiation of preadipocytes. Furthermore, MLWE treatment could dose-dependently decrease the level of triglycerides and the expressions of ACC, FAS, TNF-α, and IL-6, and up-regulate the level of glycerol and the expressions of PPARα, Adiponectin (ADPN), Adiponectin Receptor (AdipoR) 1, AdipoR2, AMPK, HSL, and IL-10 in the development of mature adipocytes. Untargeted metabolomics showed that a total of 5 and 18 differential metabolites were reversed by MLWE intervention in the differentiation of preadipocytes and the development of mature adipocytes, respectively, which involved in the biosynthesis of unsaturated fatty acids, arachidonic acid metabolism and glycerophospholipids metabolism.

Conclusion: Taken together, this study firstly verified that MLWE could effectively alleviate lipid accumulation and inflammation by regulating ADPN/AMPK-mediated signaling pathways and relevant metabolic disturbances including biosynthesis of unsaturated fatty acids, arachidonic acid metabolism and glycerophospholipids metabolism.

Keywords

3T3-L1 adipocytes; AMPK; Inflammation; Lipids metabolism; Metabolomics.

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