Singlet Oxygen Induced Products of Linoleates, 10- and 12-(Z,E)-Hydroxyoctadecadienoic Acids (HODE), Can Be Potential Biomarkers for Early Detection of Type 2 Diabetes

Abstract

Current diagnostic tests such as glycemic indicators have limitations for early detection of impaired glucose tolerance (IGT), which leads to diabetes. Oxidative stress induced by various oxidants in a random and destructive manner is considered to play an important role in the pathophysiology of a number of human disorders and diseases such as impaired glucose tolerance. We have developed an improved method for the measurement of in vivo lipid peroxidation, where the presence of 8-iso-prostaglandin F2α (8-iso-PGF2α), hydroxyoctadecadienoic acids (HODEs), hydroxyeicosatetraenoic acids (HETEs), and 7-hydroxycholesterol (7-OHCh), as well as their parent molecules, linoleic acid (LA) and cholesterol (Ch), was determined by performing LC-MS/MS (for 8-iso-PGF2α, HODE, and HETE) and GC-MS (for 7-OHCh, LA, and Ch) after reduction with triphenyl phosphine and saponification by potassium hydroxide. We then applied this method to volunteers (n = 57), including normal type (n = 43), “high-normal” (fasting plasma glucose, 100–109 mg/dL, n = 7), pre-diabetic type (IGT, n = 5), and diabetic type (n = 2) subjects who are diagnosed by performing oral glucose tolerance tests (OGTTs). Several biomarkers in plasma, such as insulin, leptin, adiponectin, interleukin-6, tumor necrosis factor-α, high sensitivity-C-reactive protein, HbA1c, and glucose levels were measured during OGTT. We found that the fasting levels of (10- and 12-(Z,E)- HODE)/LA increased significantly with increasing levels of HbA1c and glucose during OGTT and with insulin secretion and resistance index. In conclusion, 10- and 12-(Z,E)-HODE may be prominent biomarkers for the early detection of IGT and “high-normal” type without OGTT.

Comprehensive analysis of PPARγ agonist activities of stereo-, regio-, and enantio-isomers of hydroxyoctadecadienoic acids

“…Our measurement revealed that HODE isomers can be prominent biomarkers for some diseases [4][5][6][7]. For example, plasma levels of 10-and 12-(Z,E)-HODEs, which are singlet oxygen-specific products, are significantly correlated with glucose levels in patients with early-stage type 2 diabetes [6,7].…”

“…As HODEs, the reduced forms of HPODEs, are stable under physiological conditions, we developed a method to measure HODE isomers in the same sample, including 9-(Z,E) and 9-(E,E)-HODE, 10-(Z,E)-HODE, 12-(Z,E)-HODE, and 13-(Z,E) and 13-(E,E)-HODE, to understand the oxidation mechanism in vivo [2,3]. Our measurement revealed that HODE isomers can be prominent biomarkers for some diseases [4][5][6][7]. For example, plasma levels of 10-and 12-(Z,E)-HODEs, which are singlet oxygen-specific products, are significantly correlated with glucose levels in patients with early-stage type 2 diabetes [6,7].…”

Chemistry of Lipid Peroxidation Products and Their Use as Biomarkers in Early Detection of Diseases

“…4 . Recently, we found that singlet oxygen-specific products 10-and 12-HODEs are promising biomarkers for the early detection of diabetes 27 , which is discussed in more detail later. Furthermore, we have demonstrated that sublethal concentrations of racemic 10-and 12-HODEs exert cytoprotective effects in vitro.…”

“…Strikingly, 10-and 12-HODE levels in the plasma of healthy volunteers Normal were similar, suggesting that singlet oxygen attacks 10-and 12-positions of linoleates equally Table 1, unpublished data calculated from ref. 27 . It is interesting to note that 10-HODE levels tended to increase with decreasing glucose tolerance, more noticeable than 12-HODE although not significant.…”

DHA concentration of red blood cells is inversely associated with markers of lipid peroxidation in men taking DHA supplement

“…(52,53) Briefly, after an extraction with chloroform and ethyl acetate, t8-iso-PGF 2α , t-HETE, and t-HODE in plasma and RBCs were analyzed by LC-MS/MS. LC was carried out on an ODS column in a column oven set at 30°C.…”