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Role of Advanced Glycation End Products (AGEs) in Adipogenesis in Senescent Preadipocytes
Author(s) -
Chen ChihYu,
Moon Yang Soo,
Kim KeeHong
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.971.43
Subject(s) - adipogenesis , rage (emotion) , glycation , endocrinology , medicine , downregulation and upregulation , receptor , oil red o , chemistry , inflammation , adipose tissue , biology , biochemistry , gene , neuroscience
Obesity contributes to the development of metabolic syndromes and accelerates to onset of multiple aging‐related disorders. Adipogenesis is the main process to increase not only lipid accumulation, but also elevate inflammation and oxidative stress. Within aging, preadipocyte capacity to replicate and differentiate declines. Advanced glycation end products (AGEs), through its receptor (RAGE), have been shown to be implicated to aging‐associated chronic diseases. The inhibition of the AGE‐RAGE interaction has been proposed as a target to treat or prevent these diseases; however the role of AGE‐RAGE axis in obesity has not been delineated. The objective of this study was to characterize the function of AGE‐RAGE axis in adipogenic capacity of senescent 3T3‐L1 preadipocytes. We found that the high passage preadipocytes (HPP) (more than 15 passages) exhibited the elevated levels of replicative senescent markers, including upregulation of tumor suppressor protein 53, interleukin‐6 levels and beta‐galactosidase activity compared to low passage cells (equals to or less than 5 passages). Additionally, HPP had reduction of insulin sensitivity and adipogenic ability. Interestingly, HPP treated with AGEs restored adipogenic capacity assessed by Oil Red O staining and increased adipogenic gene expression such as peroxisome proliferator‐activated receptor gamma, CAATT/enhancer binding protein alpha, and fatty acid synthase. Moreover, AGE‐stimulated adipogenesis in HPP is related to increased RAGE protein expression. We further demonstrated that the blockage of RAGE by a neutralizing antibody blunted the pro‐adipogenic function of AGEs. Taken together, our results suggest that AGEs induce adipogenesis in a RAGE‐dependent manner in senescent preadipocytes. Grant Funding Source : Scholarship from the Ministry of Education of Taiwan