Protein profiling of low‐density lipoprotein from obese subjects

Abstract

Although obesity and high levels of low-density lipoprotein (LDL) are well-known risk factors for cardiovascular disease, the precise role(s) of different LDL constituents in obesity has not been explored. In the present study, we compared the LDL proteome of healthy control adults (body mass index<25) and obese subjects (body mass index>30). LDL was isolated by density-gradient ultracentrifugation and proteins were separated with 2-D PAGE, quantified, and identified by peptide mass fingerprinting using MALDI-TOF MS. A new LDL-associated protein was identified as transthyretin and found to be significantly more abundant in LDL from the obese subjects. In addition, LDL from the obese subjects contained relatively more α(1) -antitrypsin, apo J, apo C-II, than LDL from controls, and also more of an acidic isoform (pI/Mr; 5.2/23 100) of apo A-I. On the other hand, the relative amounts of apo A-IV and the major isoform of apo A-I (pI/Mr; 5.3/23 100) were significantly less in LDL from the obese subjects. Apo E was less and non-sialylated apo C-III more abundant in LDL from obese men than control men, while there were no such differences between LDL from obese and control women. These findings illustrate that obesity is not only associated with increased LDL-cholesterol levels but also with alterations in the LDL protein composition. The presence of transthyretin in LDL from obese subjects may reflect over-nutrition and affect the lipid metabolism in obesity.

Clusterin/apolipoprotein J binds to aggregated LDL in human plasma and plays a protective role against LDL aggregation

“…Although all proteomic analyses performed in LDL have detected the presence apoJ in this lipoprotein, few studies have investigated the role of apoJ on LDLs. Karlsson et al reported that apoJ is increased in LDLs from obese subjects (54), and Pettersson et al described increased apoJ content in small dense LDLs from patients with diabetes and metabolic syndrome (20). These findings suggest that the low content of apoJ in HDLs in these patients could be caused by an altered distribution of apoJ among the lipoprotein fractions.…”

Structure of HDL: Particle Subclasses and Molecular Components

“…Moreover, a recent MS study of 96 serum samples showed that 30 % of the individuals displayed an apoC-III pattern with additional glycosylated variants, characterised by fucosylation (Nicolardi et al 2013b). The relevance of these glycosylated non-sialylated variants of apoC-III, as of the C-terminal truncated forms, is yet unclear, but may explain somewhat contradictory results showing higher relative levels of non-and lesssialylated apoC-III in obese subjects than in lean subjects (Harvey et al 2009;Karlsson et al 2009), although obesity is generally associated with high triglyceride levels.…”

“…An early report suggested deamidation of Gln or Asn residues, resulting in a +1 charge shift, which could be formed during the analytical procedure (Ghiselli et al 1985). At the same time, a few reports indicated the importance of acidic apoA-I in vivo; increased levels of acidic apoA-I, while decreased levels of the major form, were found in LDL from obese subjects, especially in women (Karlsson et al 2009). Also, higher degree of deamidated apoA-I has been shown in relation to diabetes (Jaleel et al 2010) and acidic apoA-I may be more vulnerable to methionine oxidation (Fernandez-Irigoyen et al 2005).…”

LDL-associated apolipoprotein J and lysozyme are associated with atherogenic properties of LDL found in type 2 diabetes and the metabolic syndrome

“…Recently, Karlsson et al. [31] showed increased amounts of apoJ and apoCIII and a decreased amount of apoA1 in LDL from obese individuals with elevated serum lipids. Davidsson et al.…”

“…From these results of this study, we therefore conclude that apoJ is enriched on smaller LDL particles with an increased amount of apoCIII and a decreased amount of cholesterol in individuals with T2DM, and we suggest that these LDL particles are small dense LDL. Recently, Karlsson et al [31] showed increased amounts of apoJ and apoCIII and a decreased amount of apoA1 in LDL from obese individuals with elevated serum lipids. Davidsson et al [4] found an increased amount of apoCIII and a decreased amount of apoA1 in small dense LDL from individuals with T2D, elevated serum triglycerides and decreased HDL cholesterol.…”