Research highlight: Investigating obesity treatments and apoB

There is an established body of evidence linking obesity to an increased risk of cardiovascular disease (CVD). Individuals with obesity typically exhibit dyslipidemia, including increased levels of apolipoprotein B (apoB), decreased levels of high-density lipoproteins (HDL) and altered particle composition of low-density lipoproteins (LDL). Recent studies have suggested that measuring circulating apoB levels could be a potentially more effective risk marker for CVD than screening LDL levels. Measurements of apoB levels provide clinicians with information on all atherogenic lipoproteins (VLDL, LDL and IDL) and apoB molecules have a 1:1 ratio with the number of atherogenic lipoprotein particles present. Conventional cholesterol tests typically only measure levels of LDLs, therefore failing to take into account very-low density lipoproteins (VLDL) and intermediate-density lipoprotein (IDL) levels. 

Elevated levels of apoB have been linked with atherosclerosis and structural vascular changes (e.g. enlarged carotid intima-media thickness). Liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has been found to reduce cardiovascular mortality in individuals with type 2 diabetes and has been approved as a weight loss treatment. It is thought that liraglutide regulates intestinal lipid absorption by downregulating apoB48, and therefore may improve a person’s atherogenic risk profile by reducing plasma concentrations of apoB. 

In this study, Engelbrechtsen and colleagues profiled metabolic markers in 58 obese participants before and after an 8-week regime of a low-calorie diet, and over a 1 year follow-up. In the follow-up, individuals were randomly assigned a weight maintenance program with meal replacements containing liraglutide or placebo. Metabolic profiling was used to analyze lipid profile changes in both groups at screening (pre-weight loss), baseline (post-weight loss) and after 1 year of weight maintenance. 

It was found that after the 8-week diet regime, participants exhibited extensive changes in their lipid profiles, including reduced levels of apoB, triglycerides, LDLs and VLDLs. In the follow-up, lipid profiles of both groups broadly returned to pre-weight loss levels. Notably, apoB levels remained low in the liraglutide group, exhibiting an association between liraglutide and apoB.

These results indicate that the cardio-beneficial reductions in apoB, LDL and triglycerides achieved by weight loss could potentially be maintained by supplementing diet regimes with liraglutide. The apoB-lowering effect of liraglutide may be independent of weight loss and may also directly affect the dietary uptake of lipids from the intestine (or through a reduction in hepatic lipid production). Treatment with liraglutide could potentially contribute to a reduction in cardiovascular mortality, as has been previously demonstrated in liraglutide-treated subjects with type 2 diabetes. Overall, these findings lend further credence to recommendations supporting the routine screening of patient apoB levels.

This study is an example of Nightingale's NMR metabolomics platform being applied in CVD research. Nightingale's platform has been successfully used in a wide range of research applications and has been featured in over 100 peer-reviewed studies. Nightingale’s blood analysis service can be utilized to investigate drug target mechanism of action, using metabolic profiling to investigate potential effects on lipids. In this study, Nightingale’s platform was used to quantify metabolic measures, including detailed lipid and lipoprotein particle profiles, for 58 obese individuals.

Extra reading:

Access to the full paper can be found here.