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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #319739
Title: Phloretin promotes adipocyte differentiation in vitro and improves glucose homeostasis in vivo

Author
item SHU, GANG - South China Agricultural University
item LU, NAI-SHENG - South China Agricultural University
item ZHU, XIAO-TONG - South China Agricultural University
item XU, YONG - Children'S Nutrition Research Center (CNRC)
item DU, MIN-QING - South China Agricultural University
item XIE, QIU-PING - South China Agricultural University
item ZHU, CAN-JUN - South China Agricultural University
item XU, QI - South China Agricultural University
item WANG, SONG-BO - South China Agricultural University
item WANG, LI-NA - South China Agricultural University
item GAO, PING - South China Agricultural University
item XI, QIAN-YUN - South China Agricultural University
item ZHANG, YONG-LIANG - South China Agricultural University
item JIANG, QING-YAN - South China Agricultural University

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/21/2014
Publication Date: 12/24/2014
Citation: Shu, G., Lu, N., Zhu, X., Xu, Y., Du, M., Xie, Q., Zhu, C., Xu, Q., Wang, S., Wang, L., Gao, P., Xi, Q., Zhang, Y., Jiang, Q. 2014. Phloretin promotes adipocyte differentiation in vitro and improves glucose homeostasis in vivo. Journal of Nutritional Biochemistry. 25(12):1296-1308.

Interpretive Summary: Obesity and its associated insulin resistance are serious global health problems. Here we showed that an extract from plants, namely phloretin, can increase insulin sensitivity in fat cells. We further determined how phloretin may regulate fat cell functions, and how these function may benefit obese animals to increase their sensitivity to glucose-lowering effects of insulin. These findings suggest that phloretin or its analogs could be used to treat insulin resistance associated with obesity.

Technical Abstract: Adipocyte dysfunction is associated with many metabolic diseases such as obesity, insulin resistance and diabetes. Previous studies found that phloretin promotes 3T3-L1 cells differentiation, but the underlying mechanisms for phloretin's effects on adipogenesis remain unclear. In this study, we demonstrated that phloretin enhanced the lipid accumulation in porcine primary adipocytes in a time-dependent manner. Furthermore, phloretin increased the utilization of glucose and nonesterified fatty acid, while it decreased the lactate output. Microarray analysis revealed that genes associated with peroxisome proliferator-activated receptor-y (PPARy), mitogen-activated protein kinase and insulin signaling pathways were altered in response to phloretin. We further confirmed that phloretin enhanced expression of PPARy, CAAT enhancer binding protein-a (C/EBPa) and adipose-related genes, such as fatty acids translocase and fatty acid synthase. In addition, phloretin activated the Akt (Thr308) and extracellular signal-regulated kinase, and therefore, inactivated Akt targets protein. Wortmannin effectively blocked the effect of phloretin on Akt activity and the protein levels of PPARy, C/EBPa and fatty acid binding protein-4 (FABP4/aP2). Oral administration of 5 or 10 mg/kg phloretin to C57BL BKS-DB mice significantly decreased the serum glucose level and improved glucose tolerance. In conclusion, phloretin promotes the adipogenesis of porcine primary preadipocytes through Akt-associated signaling pathway. These findings suggested that phloretin might be able to increase insulin sensitivity and alleviate the metabolic diseases.