Abstract
Aging is characterized by mild hyperglycemia and accumulation of advanced glycation end products (AGEs). Effects of chronic exposure to hyperglycemia or AGEs on the adipogenic differentiation of 3T3-L1 preadipocytes remain unclear. We examined the chronic effect of AGEs and high glucose on the differentiation of 3T3-L1 cells by culturing 3T3-L1 cells in the presence of AGEs or 25 mM glucose for 1 month. Chronic incubation of 3T3-L1 cells with AGEs or high glucose blocked their differentiation into mature adipocytes as evidenced by reduced levels of adipocyte markers such as accumulated oil droplets, GPDH, aP2, adiponectin and of adipogenesis regulators PPARγ and C/EBPα. Levels or activities of Src, PDK1, Akt, and NF-κB were higher in AGEs- and high glucose-treated cells than those in 3T3-L1 cells. Levels of Bcl-2 were elevated in AGEs- and high glucose-treated cells, and were attenuated by inhibitors of PI3-kinase, Akt and NF-κB. Moreover, adipogenesis was attenuated in 3T3-L1 cells stably expressing Bcl-2 or YAP. These results suggest that chronic AGEs and high glucose treatments up-regulate Bcl-2 and YAP via the Akt-NF-κB pathway and impair adipogenesis.
Highlights
Aging is known to attenuate the differentiating ability of preadipocytes into adipocytes [1,2,3]
Our results showed that the ability of Advanced glycation end products (AGEs)- and high glucose-treated 3T3-L1 cells to differentiate into mature adipocytes was impaired as these cells expressed low levels of adipocyte markers such as oil droplets, Glycerol-3-phosphate dehydrogenase (GPDH), aP2 and adiponectin and reduced levels of PPARγ and C/EBPα
We have treated 3T3-L1 cells with 100 μg/mL AGEs for one month and obtained similar results. These results indicate that AGEs and high glucose treatments inhibit adipogenesis of 3T3-L1 preadipocytes (Figure 1B)
Summary
Aging is known to attenuate the differentiating ability of preadipocytes into adipocytes [1,2,3]. Expression of transcriptional factors that regulate adipogenesis declines with aging in rat preadipocytes from various ages. Advanced glycation end products (AGEs) are formed in vivo by a non-enzymatic reaction of proteins, lipids and nucleic acids, with glucose and other reducing sugars [4,5,6,7]. AGEs accumulation occurs in many tissues during aging due to a moderate increase in fasting glucose and to long-term exposure of proteins to normoglycemic condition [8,9,10]. AGEs and mild hyperglycemia may mediate some of the inhibitory effects of aging on adipogenesis
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