Dietary carbohydrate modification alters serum metabolic profiles in individuals with the metabolic syndrome.

BACKGROUND AND AIMS: Whole-grain cereals and diets with a low glycemic index may protect against the development of type 2 diabetes and heart disease, but the mechanisms are poorly understood. We studied the effect of carbohydrate modification on serum metabolic profiles, including lipids and branched chain amino acids, and dependencies between these and specific gene expression pathways in adipose tissue. METHODS AND RESULTS: Twenty subjects with metabolic syndrome were selected from the larger FUNGENUT study population, randomized either to a diet high in oat and wheat bread and potato (OWP) or rye bread and pasta (RP). Serum metabolomics analyses were performed using ultra-performance liquid chromatography coupled to electrospray ionization mass spectrometry (UPLC/MS), gas chromatography (GC) and UPLC. In the OWP group multiple proinflammatory lysophosphatidylcholines increased, while in the RP group docosahexaenoic acid (DHA 22:6n-3) increased and isoleucine decreased. mRNA expression of stress reactions- and adipose tissue differentiation-related genes were up-regulated in adipose tissue in the OWP group. In the RP group, however, pathways related to stress reactions and insulin signaling and energy metabolism were down-regulated. The lipid profiles had the strongest association with the changes in the adipose tissue differentiation pathway when using the elastic net regression model of the lipidomic profiles on selected pathways. CONCLUSION: Our results suggest that the dietary carbohydrate modification alters the serum metabolic profile, especially in lysoPC species, and may, thus, contribute to proinflammatory processes which in turn promote adverse changes in insulin and glucose metabolism.

Serum saturated fatty acids containing triacylglycerols are better markers of insulin resistance than total serum triacylglycerol concentrations.

AIMS/HYPOTHESIS: The weak relationship between insulin resistance and total serum triacylglycerols (TGs) could be in part due to heterogeneity of TG molecules and their distribution within different lipoproteins. We determined concentrations of individual TGs and the fatty acid composition of serum and major lipoprotein particles and analysed how changes in different TGs and fatty acid composition are related to features of insulin resistance and abdominal obesity. METHODS: We performed lipidomic analyses of all major lipoprotein fractions using two analytical platforms in 16 individuals, who exhibited a broad range of insulin sensitivity. RESULTS: We identified 45 different TGs in serum. Serum TGs containing saturated and monounsaturated fatty acids were positively, while TGs containing essential linoleic acid (18:2 n-6) were negatively correlated with HOMA-IR. Specific serum TGs that correlated positively with HOMA-IR were also significantly positively related to HOMA-IR when measured in very-low-density lipoproteins (VLDLs), intermediate-density lipoproteins (IDLs) and LDL, but not in HDL subfraction 2 (HDL(2)) or 3 (HDL(3)). Analyses of proportions of esterified fatty acids within lipoproteins revealed that palmitic acid (16:0) was positively related to HOMA-IR when measured in VLDL, IDL and LDL, but not in HDL(2) or HDL(3). Monounsaturated palmitoleic (16:1 n-7) and oleic (18:1 n-9) acids were positively related to HOMA-IR when measured in HDL(2) and HDL(3), but not in VLDL, IDL or LDL. Linoleic acid was negatively related to HOMA-IR in all lipoproteins. CONCLUSIONS/INTERPRETATION: Serum concentrations of specific TGs, such as TG(16:0/16:0/18:1) or TG(16:0/18:1/18:0), may be more precise markers of insulin resistance than total serum TG concentrations.