DELAYED INTERVENTION WITH PYRIDOXAMINE IMPROVES METABOLIC FUNCTION AND PREVENTS ADIPOSE TISSUE INFLAMMATION AND INSULIN RESISTANCE

Abstract

The development of obesity is one of the largest health problems worldwide. We and others have recently demonstrated that advanced glycation endproducts (AGEs) accumulate in adipose tissue, and that they contribute to complications such as insulin resistance and type 2 diabetes via an inflammatory reaction in adipose tissue. We recently investigated the effect of a delayed PM intervention on metabolic and vascular function in high-fat diet (HFD)-induced obese mice. We found that PM-treated, HFD-induced obese mice had reduced body weight gain, hyperglycemia and hypercholesterolemia, as compared to those who were not treated with PM. Furthermore, PM treatment inhibited the expansion of adipose tissue and adipocyte hypertrophy. Adipogenesis of murine 3T3-L1 and human SGBS preadipocytes was dose-dependently reduced by PM treatment. The high expression of pro-inflammatory genes in visceral adipose tissue of the HFD group was significantly attenuated by PM. In both HFD-induced and db/db obese mice, impaired glucose metabolism and insulin resistance were prevented by supplementation with PM. Moreover, PM treatment partially prevented HFD-induced mild vascular dysfunction. In conclusion, we will discuss AGEs in obesity and will demonstrate that a delayed intervention with PM is associated with an improvement of several aspects of obesity, including metabolic dysfunction, insulin resistance and adipose tissue inflammation. These findings indicate that PM may be a potential novel intervention strategy for obesity-associated metabolic dysfunction and complications.