Phosholipid trafficking between serum-HDL-erythrocyte in various conditions associated with circadian disturbances

Abstract

Circadian disturbances are known to affect lipid metabolism. Most of the phospholipid metabolites have been shown to be under circaian control by metabolomics studies. Moreover, genes related to glycerolipid synthesis were reported to be circadianly regulated. Data from various studies revealed a relationship between glycerolipid metabolism and circadian misalignments. Some proteins responsible for transfer of phospholipids among plasma lipoproteins or membranes include phospholipid transfer proteins (PLTP), lecithin cholesterol acyltransferase (LCAT), secretory phospholipase A2 (sPLA2), endothelial lipase (EL), exhibits circadian oscillation. However no data are available as to whether circadian disturbances can influence phospholipid trafficking among HDL, erythrocytes and serum. To this end, , four conditions associated with circadian disturbances including type 2 diabetes, prediabetes with metformin usage, psoriasis and night-shift work were investigated for phospholipid trafficking. Indices of circadian misalignments, plasma melatonin and cortisol levels, were determined by ELISA and chemiluminescence methods respectively. Serum levels of PLTP, LCAT, EL and sPLA2 levels were analyzed by ELISA. Phospholipid compositions were investigated by two-dimensional HPTLC and/or HPLC. Results by HPLC indicated that PE/PC ratios in erythrocyte lysates of diabetes and metformin groups were found to be significantly lower compared to that of controls which might be associated with the lower levels of LCAT, EL and PLTP levels measured. Altered plasma melatonin levels indicated circadian misalignments in these conditions. However, in psoriasis and night-shift groups, circadian indexes did not match with the PE/PC ratios in erythrocytes as it was in diabetes and metformin groups. We therefore conclude that circadian as well as metabolic disturbances both might have a role in phospholipid trafficking.