Conventional but not high-purity dialysis fluid induces apoptosis and insulin resistance in adipocytes in vitro

Purpose: Previous study has shown an independent association of low body fat percentage and fat loss over time with higher mortality in hemodialysis (HD) patients. High-purity dialysis fluid (HPDF) used in place of conventional dialysis fluid (CDF) may decrease inflammation and improve nutritional status. Its effect on adipocytes and therefore fat storage is unclear The purpose of this study was to assess the effects of these dialysates on apoptosis and insulin resistance in cultured adipocytes to determine a basis for the superiority of HPDF. Methods: Flow cytometry and fluorescence staining were used to evaluate apoptosis in adipocytes. Insulin receptor substrate-1 (IRS-1) and -2 and serine phosphorylation of IRS-1 levels were assayed by Western blot. Tumor necrosis factor alpha (TNF alpha) levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: Although CDF contained more bacteria (66 +/- 6 CFU/mL) than HPDF (7 +/- 3 CFU/mL) and higher levels of bacterial DNA, endotoxin levels were similar Combined with uremic serum (containing high TNF alpha levels), CDF (vs. HPDF) induced more apoptosis in adipocytes. Exposure to CDF also decreased expression of IRS-1 protein, increased expression of IRS-2 protein and insulin-stimulated serine phosphorylation of IRS-1, and decreased glucose consumption. Additionally, the culture supernatant from adipocytes exposed to CDF plus uremic serum for 48 hours contained significantly higher levels of TNF alpha (15.17 +/- 2.89 vs. 8.12 +/- 0.54 pg/mL [HPD plus uremic serum], p<0.0001). Conclusion: The advantage of HPDF over CDF may be due to lower levels of dialysis fluid impurities.