Impact of bariatric surgery-induced weight loss on circulating PCSK9 levels in obese patients

BACKGROUND AND AIMS: To investigate the effect of obesity and bariatric-induced weight loss on circulating levels of proprotein convertase subtilisin/kexin 9 (PCSK9) in severely obese patients.METHODS AND RESULTS: In this non-randomized interventional study, we enrolled 36 severely obese patients (BMI 43.7±5.6kg/m2), of which 20 underwent bariatric surgery, and 12 nonobese healthy controls. An oral glucose tolerance test (75-g OGTT) was performed in 31 of these obese patients at baseline (T0) and in 14 patients at 6 months after bariatric surgery (T6) to assess plasma glucose, insulin and PCSK9 levels. Plasma PCSK9 levels were also measured in 18 of these obese patients at T0 during a 2-hhyperinsulinemic-euglycemic clamp (HEC). At T0, PCSK9 levels were higher in obese patients than in controls (274.6±76.7ng/mL vs. 201.4±53.3ng/mL) and dropped after bariatric surgery (T6; 205.5±51.7ng/mL) along with BMI (from 44.1±5.9kg/m2 to 33.1±5.6kg/m2). At T6, there was also a decrease in plasma glucose (T0 vs. T6: 6.0±1.8 vs. 5.0±0.5mmol/L) and insulin (15.7±8.3 vs. 5.4±2.1mU/L) levels. At T0, plasma PCSK9 levels decreased during OGTT in obese patients, reaching a nadir of 262.0±61.4ng/mL at 120min with a hyperinsulinemic peak of 75.1±40.0mU/L, at 60min. Similarly, at T0 insulin infusion during 2-hHEC acutely reduced plasma PCSK9 levels in obese patients. The aforementioned OGTT-induced changes in plasma PCSK9 levels were not observed neither in nonobese healthy controls nor in obese patients after bariatric-surgery weight loss.CONCLUSIONS: These results suggest a pivotal role of adipose tissue and insulin resistance on PCSK9 homeostasis in severely obese patients.