Obesity alters VLDL profile and remnant cholesterol differently in metabolically healthy men and women: a ¹H-NMR study.

Background and aims: Lipoprotein particle (p) size and count beyond lipoprotein lipid content [triglycerides (tg) and cholesterol (c)] are critical for their atherogenicity. This study characterized lipoprotein profiles in metabolically healthy individuals with overweight or obesity and assessed the impact of sex, obesity, and lipid background.

Methods: Proton-nuclear magnetic resonance (¹H-NMR) was used to assess the composition of very low-, low-, intermediate-, and high-density lipoproteins (VLDL, LDL, IDL, HDL), and particle number and size of VLDL, LDL, and HDL in 101 healthy subjects with overweight and obesity.

Results: Men showed significantly higher VLDLc and VLDLtg levels, counts of VLDLp (all subfractions) and LDLp (total and small), and smaller LDLp size, compared to women. Men had lower HDLc and HDLp (total and medium). In Obesity (Ob) compared to overweight (Ov), VLDLp number, VLDLtg and remnant cholesterol (RC) levels were significantly increased [Fold changes (FC) Ob.vs.Ov: 1.45, 1.39, and 1.26, respectively]. When stratified by sex, obesity-related VLDL and IDL profile deterioration was evident only in women. Individuals with LDLc ≥ 130 mg/dL showed increased RC compared to those with LDLc < 130 mg/dL (FC:1.26). The median 10-year cardiovascular disease (CVD) risk REGICOR was low (2%), but higher in men and in obesity. Individuals with higher CVD risk showed increased VLDLc, VLDLtg, VLDLp, and RC levels.

Conclusion: Men had a higher 10-year CVD risk and a less favorable triglyceride-rich lipoprotein and RC profile, while obesity aggravated these patterns, particularly in women. These findings support considering high-risk lipoprotein patterns in targeted CVD prevention for overweight and obese populations.