linoleic-acid and lysophosphatidylinositol

Metabolomics has provided new insight into diabetes risk assessment. In this study we characterised the human serum metabolic profiles of participants in the Singapore Chinese Health Study cohort to identify metabolic signatures associated with an increased risk of type 2 diabetes.. In this nested case-control study, baseline serum metabolite profiles were measured using LC-MS and GC-MS during a 6-year follow-up of 197 individuals with type 2 diabetes but without a history of cardiovascular disease or cancer before diabetes diagnosis, and 197 healthy controls matched by age, sex and date of blood collection.. A total of 51 differential metabolites were identified between cases and controls. Of these, 35 were significantly associated with diabetes risk in the multivariate analysis after false discovery rate adjustment, such as increased branched-chain amino acids (leucine, isoleucine and valine), non-esterified fatty acids (palmitic acid, stearic acid, oleic acid and linoleic acid) and lysophosphatidylinositol (LPI) species (16:1, 18:1, 18:2, 20:3, 20:4 and 22:6). A combination of six metabolites including proline, glycerol, aminomalonic acid, LPI (16:1), 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid and urea showed the potential to predict type 2 diabetes in at-risk individuals with high baseline HbA1c levels (≥6.5% [47.5 mmol/mol]) with an AUC of 0.935. Combined lysophosphatidylglycerol (LPG) (12:0) and LPI (16:1) also showed the potential to predict type 2 diabetes in individuals with normal baseline HbA1c levels (<6.5% [47.5 mmol/mol]; AUC = 0.781).. Our findings show that branched-chain amino acids and NEFA are potent predictors of diabetes development in Chinese adults. Our results also indicate the potential of lysophospholipids for predicting diabetes.

Topics: Amino Acids, Branched-Chain; Asian People; Blood Glucose; Case-Control Studies; Chromatography, Liquid; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Furans; Gas Chromatography-Mass Spectrometry; Glycated Hemoglobin; Glycerol; Humans; Linoleic Acid; Lysophospholipids; Metabolomics; Oleic Acid; Proline; Propionates; Urea

The mechanism of the previously reported cytotoxicity of liposomes containing plant phosphatidylinositol (PI) against numerous tumor cell lines was examined in detail by using liposomes containing synthetic PI specifically labeled either with radioactive myo-inositol, or in the sn-2 position with radioactive linoleic acid, oleic acid, or arachidonic acid. The uptake of liposomal PI by N4TG1 neuroblastoma cells increased with time and was dependent on the nature of the fatty acids. Uptake was highest with liposomal PI containing linoleic acid followed by arachidonic acid and then by oleic acid. The cellular fate of liposomal PI was determined by analysis of radioactive metabolites present in extracts of tumor cell lipids. Appearance of liposomal PI metabolic products in the tumor cells was correlated with thymidine uptake as a measure of viability. After 3 h incubation of cells with PI liposomes it was found that the release of both radioactive liposomal fatty acids (and probably also lyso-Pl) and radioactive diglycerides was correlated inversely with the cellular uptake of [methyl-3H]thymidine and uptake of [3H]myoinositol. An experiment in which liposomes were prepared both from animal Pl which contained predominantly saturated fatty acids in the sn-2 position and an increasing mole fraction of a synthetic Pl containing radioactive linoleic acid in the sn-2 position established that the amount of Pl containing linoleic acid in the sn-2 position could be correlated with a decrease in the amount of thymidine uptake by tumor cells. The above results clearly established that phospholipases A2 and C in the tumor cells were responsible for the formation of metabolites of liposomal Pl, and these metabolic products might have been responsible for cytotoxicity and cell death.

Topics: Animals; Cell Line; Linoleic Acid; Linoleic Acids; Liposomes; Lysophospholipids; Mice; Neoplasms, Experimental; Phosphatidylinositols