In patients living with obesity, low-density lipoprotein (LDL) does not function normally increasing the risk of cardiovascular disease (CVD). However, in patients who underwent bariatric surgery, the quality of their LDL clearly correlated with weight loss and the closer the patient's weight was to ‘normal’, the lower their risk of CVD, according to Boston University Chobanian & Avedisian School of Medicine researchers.
"Our results showed that in obesity, it is not the quantity but the quality of LDL that contributes to disease: 'bad cholesterol' becomes worse due to obesity-associated inflammation,” explained corresponding author, Dr Shobini Jayaraman, a senior research scientist in pharmacology, physiology and biophysics. “As a result, cholesterol delivery is shifted from normal to abnormal, so more cholesterol is retained in the arterial wall, ultimately forming plaques that occlude the blood flow."
In the study, blood lipoproteins from patients with severe obesity before bariatric surgery and six or 12 months after were compared with lipoproteins from a control group of lean healthy subjects. The researchers then explored lipoprotein interactions with three cell receptors key to LDL function. This included LDL receptor (which directs normal uptake of cholesterol by cells) and two scavenger receptors (which can cause harmful cholesterol accumulation).
They then designed an assay to quantify lipoprotein interactions with many extracellular matrix components. These interactions can promote harmful lipoprotein retention in the arteries, which can cause atherosclerosis. Additionally, they analysed LDL composition and used liquid chromatography and other biochemical methods to explore nanoparticle charge and aggregation, which influence LDL functionality.
In patients with obesity, they found LDL particles became dysfunctional and were less efficient at delivering their cholesterol cargo to LDL receptors. Additionally, the LDL particle also tended to either preferentially deliver cholesterol to scavenger receptors or stick to the arterial wall matrix.
"This aberrant behaviour stemmed from alterations in LDL biochemical composition induced by obesity-associated inflammation. These harmful changes contributed to increased risk of CVD in patients with obesity," added Jayaraman.
According to the researchers, during the first year after the bariatric surgery the patients lost a lot of weight, the obesity-induced inflammation subsided, and the LDL quality progressively improved six and 12 months post-operatively. Still, the LDL quality did not reach the levels of lean controls and neither did the BMI. However, LDL quality clearly correlated with weight loss, the closer the patient's weight was to normal, the better was their LDL quality, resulting in a lowered risk of CVD.
"Our study shows that LDL quality continues to improve as a patient's weight normalises, suggesting that the risk of CVD continues to decline,” said senior author, Dr Olga Gursky, professor of pharmacology, physiology and biophysics at the school. “This is promising not only for patients undergoing bariatric surgery but perhaps for many others who are overweight or obese and use various approaches to weight loss."
All clinical and some biochemical studies were performed by the Barcelona team led by Dr Jose Luis Sanchez Quesada, the co-corresponding author on this study.
The findings were featured in the paper, ‘LDL binding to cell receptors and extracellular matrix is proatherogenic in obesity but improves after bariatric surgery’, published in the Journal of Lipid Research.
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