Formation of advanced glycation end products (AGE) in vitro and their impact on adipocyte function
Obesity is a growing epidemic around the world and is associated with many health risks, including inflammation, metabolic syndrome, and insulin resistance. Expansion of white adipose tissue (WAT) by adipocyte hypertrophy and hyperplasia is a known cause of obesity. Due to the large amount of negative aspects with this disease, previous research has extensively focused on determining mechanisms and factors that accelerate obesity and its health risks. Advanced glycation end products (AGEs), formed during the Maillard reaction, are commonly found in the body and in many food products. AGEs, through their receptor (RAGE), are known to induce oxidative stress, inflammation, and chronic diseases, including diabetes and cardiovascular disease. As a result, proposed treatments have focused on inhibiting the AGE-RAGE interaction, yet little is known about their effects on obesity. The objectives of our study were to characterize AGEs prepared in vitro and to examine the role of AGEs on adipocyte function using 3T3-L1 cells as an in vitro model of adipose tissue. Using bovine serum albumin (BSA) as an in vitro model of the Maillard reaction, we generated AGEs with two substrates, methylglyoxal (MG) and glyceraldehyde (GA). The solutions were characterized as AGEs using spectroscopy and native polyacrylamide gel electrophoresis. Although previous research linked AGEs to oxidative stress, we did not observe any effect on intracellular reactive oxygen species as a result of either AGE condition; however, both AGE preparations caused significant changes to adipocyte gene expression. In mature adipocytes, GA-BSA mRNA expression suggested the induction of oxidative stress and the increase in mitochondrial biogenesis in response, but MG-BSA had a low level of all adipocyte genes measured, suggesting cellular dysfunction. Both preparations also caused a slight increase in lipid accumulation during adipogenesis. These results suggest that AGEs modulate adipocyte function, which implicates their role in obesity-related diseases. Therefore, a dietary reduction or inhibition of formation of AGEs may be beneficial in the prevention of the detrimental health effects associated with obesity.
Kim, Purdue University.
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