α-Naphthoflavone Increases Lipid Accumulation in Mature Adipocytes and Enhances Adipocyte-Stimulated Endothelial Tube Formation.
The aryl hydrocarbon receptor (AhR) is a ligand-activated factor that regulates biological effects associated with obesity. The AhR agonists, such as environmental contaminants 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and β-naphthoflavone (BNF), inhibit preadipocyte differentiation and interfere with the functions of adipose tissue, whereas the antagonist may have opposite or protective effects in obesity. This study investigated the effects of α-naphthoflavone (α-NF), an AhR antagonist, on adipogenesis- and angiogenesis-associated factors in mature adipocytes and on cross-talk of mature adipocytes with endothelial cells (ECs). Besides, the roles of the AhR on lipid accumulation and on secretion of vascular endothelial growth factor were also determined by introducing siRNA of AhR. Differentiated 3T3-L1 cells were treated with α-naphthoflavone (α-NF) (1-5 μM) for 16 h. Lipid accumulation and the expressions of AhR-associated factors in the cells were determined. The interaction between adipocytes and ECs was investigated by cultivating ECs with conditioned medium (CM) from α-NF-treated mature adipocytes, followed by the determination of endothelial tube formation. The results showed that α-NF significantly increased triglyceride (TG) accumulation in mature adipocytes, which was associated with increased expression of hormone-sensitive lipase (HSL), estrogen receptor (ER), as well as decreased expression of AhR, AhR nuclear translocator (ARNT), cytochrome P4501B1 (CYP1B1), and nuclear factor erythroid-2-related factor (NRF-2) proteins. In addition, CM stimulated formation of tube-like structures in ECs, and α-NF further enhanced such stimulation in association with modulated the secretions of various angiogenic mediators by mature adipocytes. Similarly, increased TG accumulation and vascular endothelial growth factor (VEGF) secretion were observed in AhR-knockout cells. In conclusion, α-NF increased TG accumulation in mature adipocytes and enhanced mature adipocyte-stimulated tube formation in ECs, suggesting that the AhR may suppress obesity-induced adverse effects, and α-NF abolished the protective effects of the AhR.
School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan. b8706083@tmu.edu.tw.
Mei-Lin
ML
Wang
School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan. lin5611@tmu.edu.tw.
Shyh-Hsiang
SH
Lin
Department of Food and Beverage Management, Mackay Medicine, Nursing and Management College, Taipei 112, Taiwan. s212@eip.mkc.edu.tw.
Yuan-Yu
YY
Hou
School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan. yuehwa@tmu.edu.tw.|Cancer Research Center, Taipei Medical University Hospital, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan. yuehwa@tmu.edu.tw.
Yue-Hwa
YH
Chen
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001571:Benzoflavones / Q000494:pharmacology*; D065633:Cytochrome P-450 CYP1B1 / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D001571:Benzoflavones; D065633:Cytochrome P-450 CYP1B1; D008049:Lipase; D050984:NF-E2 Transcription Factor, p45 Subunit; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; D014280:Triglycerides; D042442:Vascular Endothelial Growth Factors; C484722:Ahr protein, mouse; C494693:Nfe2 protein, mouse; C011512:alpha-naphthoflavone