Metabolomic analysis of polar metabolites in lipoprotein fractions identifies lipoprotein-specific metabolic profiles and their association with insulin resistance

Abstract

While the molecular lipid composition of lipoproteins has been investigated in detail, little is known about associations of small polar metabolites with specific lipoproteins. The aim of the present study was to investigate the profiles of polar metabolites in different lipoprotein fractions, i.e., very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and two sub-fractions of the high-density lipoprotein (HDL). The VLDL, IDL, LDL, HDL(2), and HDL(3) fractions were isolated from serum of sixteen individuals having a broad range of insulin sensitivity and characterized using comprehensive two-dimensional gas chromatography combined with time-of-flight mass spectrometry (GC×GC-TOFMS). The lipoprotein fractions had clearly different metabolite profiles, which correlated with the particle size and surface charge. Lipoprotein-specific associations of individual metabolites with insulin resistance were identified, particularly in VLDL and IDL fractions, even in the absence of such associations in serum. The results indicate that the polar molecules are strongly attached to the surface of the lipoproteins. Furthermore, strong lipoprotein-specific associations of metabolites with insulin resistance, as compared to their serum profiles, indicate that lipoproteins may be a rich source of tissue-specific metabolic biomarkers.

Improved Metabolic Health Alters Host Metabolism in Parallel with Changes in Systemic Xeno-Metabolites of Gut Origin

“…Other reported markers of insulin resistance or T2D primarily from cross-sectional studies include increased fasting blood or urine stearoyl-CoA desaturase-derived fatty acids, glucose derivatives and gluconeogenic precursors, bile acids or derivatives, cystine-cysteine (e.g., [5], [7], [8], [15], [16], [69], [70]), and decreased glycine, glutamine, L-GPC, and arachidonic acid (e.g., [5], [7]–[9], [13], [15], [16], [71]). Under conditions of a glucose challenge, individuals with insulin resistance had a blunted response in terms of blood lactate, bile acid or TCA-associated organic acid increases and glycerol and β-hydroxybutyrate decreases [17], [20]).…”

Identification of compounds from high‐fat and extra virgin olive oil‐supplemented diets in whole mouse liver extracts and isolated mitochondria using mass spectrometry

“…For example, our results in the negative ion mode indicated that heneicosanoic acid ( m / z 325) was presented in standard chow, and it was incorporated by liver and liver mitochondria in control mice (Figure S1). Although the role of this fatty acid has still not been described in mitochondria, it is known that it participates as an energy source and it is also important to the membrane integrity/stability of several cell types . Similarly, linoleic acid ( m / z 279) was incorporated by the liver of mice in the control group (Figure S1).…”

“…Although the role of this fatty acid has still not been described in mitochondria, it is known that it participates as an energy source and it is also important to the membrane integrity/stability of several cell types. [34][35][36] Similarly, linoleic acid (m/z 279) was incorporated by the liver of mice in the control group ( Figure S1). This compound is an essential fatty acid, and it is known to keep the water permeability barrier.…”

A Novel Fasting Blood Test for Insulin Resistance and Prediabetes

“…Metabolomic studies in metabolic diseases 31 have been used to identify novel biomarkers that associate with IR 23,32,33 and predict T2DM. [34][35][36] The three metabolites used in the test have a number of potential roles in metabolic pathways relevant to insulin action, insulin secretion, or β-cell function.…”