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Trigonelline attenuates the adipocyte differentiation and lipid accumulation in 3T3-L1 cells
Institution:1. Graduate School of Biotechnology, Kyung Hee University, Gyeonggi, Republic of Korea;2. Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Global Campus, Gyeonggi, Republic of Korea;1. Center of Mitochondria and Healthy Aging, School of Life Sciences, Yantai University, Yantai 264005, China;2. Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xi''ning 810001, China;3. Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University, Yantai 264005, China;4. School of Life Sciences, Lanzhou University, Lanzhou 730000, China
Abstract:Trigonelline is a natural alkaloid mainly found in Trigonella Foenum Graecum (fenugreek) Fabaceae and other edible plants with a variety of medicinal applications. Therefore, we investigated the molecular mechanism of trigonelline (TG) on the inhibition of adipocyte differentiation and lipid accumulation in 3T3-L1 cells. Trigonelline suppressed lipid droplet accumulation in a concentration (75 and 100 μM) dependent manner. Treatment of adipocyte with of TG down regulates the peroxisome proliferator-activated receptor (PPARγ) and CCAAT element binding protein (C/EBP-α) mRNA expression, which leads to further down regulation of other gene such as adiponectin, adipogenin, leptin, resistin and adipocyte fatty acid binding protein (aP2) as compared with respective control cells on 5th and 10th day of differentiation. Further, addition of triognelline along with troglitazone to the adipocyte attenuated the troglitazone effects on PPARγ mediated differentiation and lipid accumulation in 3T3-L1 cells. Trigonelline might compete against troglitazone for its binding to the PPARγ. In addition, adipocyte treated with trigonelline and isoproterenol separately. Isoproterenol, a lipolytic agent which inhibits the fatty acid synthase and GLUT-4 transporter expression via cAMP mediated pathway, we found that similar magnitude response of fatty acid synthase and GLUT-4 transporter expression in trigonelline treated adipocyte. These results suggest that the trigonelline inhibits the adipogenesis by its influences on the expression PPARγ, which leads to subsequent down regulation of PPAR-γ mediated pathway during adipogenesis. Our findings provide key approach to the mechanism underlying the anti-adipogenic activity of trigonelline.
Keywords:Trigonelline  Troglitazone  Isoproterenol  Adipogenesis  cAMP  PPARγ
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