High-density lipoprotein particles undergo metabolic activation during obesity

According to research presented in an oral presentation at the IES Annual Meeting, high-density lipoprotein (HDL) particles undergo metabolic activation during obesity and become dysfunctional.

Researchers concluded that “determination of MHI (metabolic HDL index) may provide a novel indicator of metabolic health and guide clinical decision-making”.

The study was based upon a hypothesis following a study carried out on mice, which demonstrated the enrichment of pro-inflammatory proteins on HDL from obese mice, who were fed a saturated-fat diet compared with a monosaturated-fat diet. This study hypothesised that HDL function and proteomic composition would be modulated in obese humans, similarly to those of the mice.

The study was carried out with a cohort of 108 obese subjects and 129 normal-weight (NW) subjects. The obese subjects were categorised into ‘metabolically healthy obese’ (45 subjects) and ‘metabolically unhealthy obese’ (65).

Efflux function of small and large HDL particles and paraoxonase-1 activity was determined. Researchers then performed HDL-proteomic analysis on subgroups of age- and sex-matched subjects. The groups were made of eight-to-12 people.

The study found that ABCA1-independent (p<0.001) efflux to HDL and paraoxonase-1 activity (p<0.001) were reduced significantly, while ABCA1-dependent efflux was preserved in obese subjects compared with NW controls.

The metabolically unhealthy obese cohort showed an intermediate HDL-proteome footprint. An MHI score generated based upon the proteomic data could “significantly delineate” between the metabolically healthy and the metabolically unhealthy obese groups; this was “one of the strongest correlates with multiple components of the metabolic syndrome”.

This research was carried out by the UCD Diabetes Complications Research Centre, UCD Conway Institute, University College Dublin, the Department of Endocrinology at St Vincent’s University Hospital, Dublin, and Tallaght
Hospital, Dublin.