6′-O-acetyl mangiferin from Iris rossii Baker inhibits lipid accumulation partly via AMPK activation in adipogenesis. (25th September 2019)

• Record Type: Journal Article
• Authors: Sim, Mi-Ok; Lee, Hyun Joo; Jeong, Da Eun; Jang, Ji-Hun; Jung, Ho-Kyung; Cho, Hyun-Woo
• Is Part Of: Chemico-biological interactions. Volume 311(2019)
• Publication Date: 2019-09-25
• Subjects: Adenosine monophosphate-activated protein kinase -- Adipocytes -- Lipolysis -- Mangiferin -- Obesity -- β-oxidation; ACC acetyl-CoA-carboxylase -- Acsl1 acyl-CoA synthetase 1 -- AMPK adenosine monophosphate-activated protein kinase -- ATGL adipose triglyceride lipase -- NBCS New born calf serum -- C/EBPα CCAAT/enhancer binding protein-α -- DEX dexamethasone -- FABP4 fatty acid-binding protein 4 -- FBS fetal bovine serum -- FFA free fatty acid -- HSL hormone-sensitive lipase -- hMSC human mesenchymal stem cell -- IBMX 3-isobutyl-1-methylxanthine -- MTS 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium -- OAM 6′-O-acetyl mangiferin -- PPARγ peroxisome proliferator-activated receptor γ -- SREBP-1c sterol regulatory element-binding protein-1c -- WAT white adipose tissue; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2019.108755
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Effective control of white adipose tissue accumulation would provide a therapeutic strategy for obesity, which poses a growing global problem. The plant chemical mangiferin stimulates adenosine monophosphate-activated protein kinase (AMPK), which inhibits adipogenesis and has therefore been considered a therapeutic target for obesity and related diseases. We previously reported the anti-inflammatory properties of 6′-O-acetyl mangiferin (OAM). In this study, we evaluated the potential of OAM as an AMPK activator in vitro in 3T3-L1 preadipocytes. OAM inhibited adipogenesis as indicated by lower intracellular lipid and triglyceride accumulation as well as reduced adipogenic gene and protein expression upon treatment. OAM-treated 3T3-L1 cells excreted more glycerol, indicating increased lipolysis, which was supported by increased expression of lipolysis-related genes, including adipose triglyceride lipase and hormone-sensitive lipase. We determined that OAM upregulates lipolysis via phosphorylation-dependent activation of AMPK. Further, OAM upregulated the β-oxidation pathway as indicated by enhanced expression of phosphorylated acetyl-CoA-carboxylase and long-chain acyl-CoA synthetase 1. In conclusion, OAM markedly decreased intracellular lipid accumulation by enhancing lipolysis via AMPK activation and by upregulating β-oxidation. Thus, OAM has potential as a drug for the prevention and/or improvement of obesity and related diseases and deserves further study. Highlights: 6′-O-acetyl mangiferin (OAM) inhibits adipogenesis in 3T3-L1 preadipocytes. OAM markedly decreases intracellular lipid accumulation. The decrease in lipid accumulation results from enhanced lipolysis and β-oxidation. OAM induces lipolysis via adenosine monophosphate-activated protein kinase. OAM has potential as a therapeutic target for the treatment of obesity.