Kaempferol Isolated from Nelumbo nucifera Inhibits Lipid Accumulation and Increases Fatty Acid Oxidation Signaling in Adipocytes.
Stamens of Nelumbo nucifera Gaertn have been used as a Chinese medicine due to its antioxidant, hypoglycemic, and antiatherogenic activity. However, the effects of kaempferol, a main component of N. nucifera, on obesity are not fully understood. We examined the effect of kaempferol on adipogenesis and fatty acid oxidation signaling pathways in 3T3-L1 adipocytes. Kaempferol reduced cytoplasmic triglyceride (TG) accumulation in dose and time-dependent manners during adipocyte differentiation. Accumulation of TG was rapidly reversed by retrieving kaempferol treatment. Kaempferol broadly decreased mRNA or protein levels of adipogenic transcription factors and their target genes related to lipid accumulation. Kaempferol also suppressed glucose uptake and glucose transporter GLUT4 mRNA expression in adipocytes. Furthermore, protein docking simulation suggests that Kaempferol can directly bind to and activate peroxisome proliferator-activated receptor (PPAR)-α by forming hydrophobic interactions with VAL324, THR279, and LEU321 residues of PPARα. The binding affinity was higher than a well-known PPARα agonist fenofibrate. Consistently, mRNA expression levels of PPARα target genes were increased. Our study indicates while kaempferol inhibits lipogenic transcription factors and lipid accumulation, it may bind to PPARα and stimulate fatty acid oxidation signaling in adipocytes.
1 Department of Food Science and Nutrition, Pukyong National University , Busan, Korea.
Bonggi
B
Lee
1 Department of Food Science and Nutrition, Pukyong National University , Busan, Korea.
Misung
M
Kwon
1 Department of Food Science and Nutrition, Pukyong National University , Busan, Korea.
Jae Sue
JS
Choi
2 Molecular Inflammation Research Center for Ageing Intervention (MRCA), Pusan National University , Busan, Korea.
Hyoung Oh
HO
Jeong
2 Molecular Inflammation Research Center for Ageing Intervention (MRCA), Pusan National University , Busan, Korea.|3 College of Pharmacy, Pusan National University , Busan, Korea.
Hae Young
HY
Chung
1 Department of Food Science and Nutrition, Pukyong National University , Busan, Korea.
Hyeung-Rak
HR
Kim
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D044949:Kaempferols / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D031653:Nelumbo / Q000737:chemistry*; D009765:Obesity / Q000378:metabolism / Q000517:prevention & control*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism*
D005227:Fatty Acids; D051275:Glucose Transporter Type 4; D044949:Kaempferols; D047493:PPAR alpha; D010936:Plant Extracts; D012333:RNA, Messenger; C495693:Slc2a4 protein, mouse; D014280:Triglycerides; C006552:kaempferol; D005947:Glucose
adipocyte; adipogenesis; kaempferol; obesity