Molecular mechanisms underlying the anti-obesity potential of prunetin, an O-methylated isoflavone

• Published in: Biochemical pharmacology Vol. 85; no. 10; pp. 1525 - 1533
• Main Authors: Ahn, Tae-Gue, Yang, Gabsik, Lee, Heon-Myung, Kim, Myung-Dong, Choi, Ho-Young, Park, Kyoung-Sik, Lee, Sun-Dong, Kook, Yoon-Bum, An, Hyo-Jin
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 15.05.2013
• Subjects: Adipocytes - drug effects; Adipocytes - metabolism; adipogenesis; Adipogenesis - drug effects; Adipogenesis - genetics; Adipogenic genes; adiponectin; Adiponectin - antagonists & inhibitors; Adiponectin - genetics; Adiponectin - metabolism; Adiponectin receptors; adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; AMP-activated protein kinase; AMP-activated protein kinase (AMPK); AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; Animals; anti-inflammatory activity; Anti-Obesity Agents - pharmacology; blood glucose; Blood Glucose - metabolism; Diet, High-Fat - adverse effects; Feedback, Physiological; gene expression regulation; Gene Expression Regulation - drug effects; genes; high fat diet; High-fat diet (HFD); isoflavones; Isoflavones - pharmacology; leptin; Lipid Metabolism - drug effects; liver; Liver - drug effects; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; obesity; Obesity - etiology; Obesity - genetics; Obesity - metabolism; Obesity - prevention & control; Prunetin; Receptors, Adiponectin - agonists; Receptors, Adiponectin - genetics; Receptors, Adiponectin - metabolism; visceral fat; weight gain; Weight Gain - drug effects; Mice; High-fat diet (HFD); Adipogenic genes; Prunetin; Adiponectin receptors; AMP-activated protein kinase (AMPK)
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2013.02.020

Prunetin is an O-methylated isoflavone, which is a type of flavonoid. There are a limited number of reports detailing the biological activities of prunetin. Although an anti-inflammatory effect of prunetin has been reported in vitro, to our knowledge, there have been no reports on anti-adipogenic effects of prunetin in obese animals. The aims of this study were to determine whether prunetin suppresses high-fat diet (HFD)-induced adipogenesis in the liver and visceral adipose tissues of mice, and to explore the underlying mechanisms mediating the actions of prunetin. To this end, mice were fed a HFD for 10 weeks to induce obesity, and prunetin (10μg/kg or 20μg/kg) was administered in the last 3 weeks. Compared to saline-treated mice, mice treated with prunetin showed significantly reduced body weight gain, visceral fat pad weights, and plasma glucose levels. We found that prunetin significantly inhibited the HFD-induced upregulation of the expression of important adipogenic genes (PPARγ, C/EBPα, SREBP, aP2, LPL adiponectin, and leptin), and suppressed HFD-mediated increase in expression of lipid metabolism-related genes (SREBP, PPARγ, LXR, and HMG-CoA) in the liver tissues. Furthermore, prunetin induced expression of adiponectin receptors 1 and 2 (adipoR1, adipoR2), as well as that of AMP-activated protein kinase (AMPK) in the liver and adipose tissue. These results suggest that prunetin mediates anti-obesity/adipogenesis effects by suppressing obesity-related transcription through a feedback mechanism that regulates the expression of adiponectin, adipoR1, adipoR2, and AMPK.