Plasma Phospholipids with Long-Chain Polyunsaturated Fatty Acids and Dihydroceramides at the Crossroads of Iron Stores and Insulin Resistance

Scope Iron plays an important role in the pathogenesis of insulin resistance (IR) and type 2 diabetes. Recent studies suggest a role of specific lipids in the induction of IR, but the potential relationships between iron and lipid metabolites in relation to IR have not been explored. Therefore, the aim of the study is to evaluate the association among iron, IR, and the lipidome. Methods and results The plasma lipidome, IR, parameters of iron metabolism, and several cytokines and adipokines in 65 overweight/obese participants are measured. Measurements of IR correlate positively with ferritin, a measure of iron storage (r = 0.35, p = 0.005), and negatively with adiponectin (r = -0.30, p = 0.02). The serum ferritin/adiponectin ratio has a stronger association with IR (r = 0.41, p < 0.001). From multivariate analyses adjusted for age, sex, and BMI, several phospholipids containing long chain polyunsaturated fatty acids (PUFA) with 20-22 carbons (phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, and a phosphatidylserine), are positively associated with ferritin and the ferritin/adiponectin ratio. Two dihydroceramides (Cer(18:0/22:0), Cer(18:0/24:0)) and several diglycerides and triglycerides, mainly comprised of C14:0, C16:0, C18:0, C18:1, and C18:2, also have positive correlations with ferritin and the ferritin/adiponectin ratio. Conclusions The positive associations between these lipid species and ferritin or the ferritin/adiponectin ratio suggest a potential crosstalk between iron and lipid metabolism in obesity and IR.