Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 25, Issue 12, Pages 1296-1308Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2014.07.007
Keywords
Phloretin; FAT/CD36; Preadipocytes; Differentiation; Akt signaling; Glucose
Funding
- National Basic Research Program of China (Beijing) [2012CB124701, 2013CB127304]
- National Natural Science Foundation of China (Beijing) [30972157]
- Natural Science Foundation of Guangdong Province of China (Guangzhou) [S2012020011048]
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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-gamma (PPAR gamma), mitogen-activated protein kinase and insulin signaling pathways were altered in response to phloretin. We further confirmed that phloretin enhanced expression of PPAR gamma, CAAT enhancer binding protein-alpha (C/EBP alpha) 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 PPAR gamma, C/EBP alpha 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. (C) 2014 Published by Elsevier Inc.
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