Abstract 131: PCSK9: A Biomarker Associated with the Metabolic Complications of Morbid Obesity

Abstract

Objectives: Plasma pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protease that inhibits the activity of the LDL-receptor. Here, we determined the effect of bariatric surgery on plasma PCSK9 levels. Methods: Sixty-five obese patients (BMI : 46.7 ± 6.5 kg/m 2) were prospectively evaluated before and 6 months after bariatric surgery (sleeve-gastrectomy [n=53], Roux-en-Y gastric bypass [n=12], gastric banding [n=1]). Plasma PCSK9 were measured by ELISA and liver mRNA PCSK9 expression by Q-PCR. Results: Before surgery, plasma PCSK9 was positively associated with LDL-C (r=0.59, P<0.0001), plasma triglycerides (TG) (r=0.48, P=0.0006) and fasting plasma glucose (FPG) (r=0.29 ; P=0.036), and negatively with BMI (r =-0.34, P=0.01). Plasma PCSK9 concentrations were increased in obese patients with metabolic syndrome (MetS) compared to those without MetS (295 ± 93 vs 210 ± 58 ng/ml, P<0.0001). Bariatric surgery did not alter plasma PCSK9 concentrations at 6 months. Interestingly, circulating PCSK9 was not longer correlated with LDL-C after bariatric surgery, but remained strongly associated with TG (r=0.50 P=0.0006), FPG (r=0.40 P=0.006) and HOMA-IR (r=0.40 P=0.007). Plasma PCSK9 levels were positively associated with liver steatosis (r=0.26, P=0.05), and were higher in patients with NASH (347 ± 101 vs 228 ± 73 ng/ml, P=0.003). Surprisingly, PCSK9 hepatic mRNA expression did not correlate with plasma PCSK9 concentrations, neither with LDL-C nor TG. Conclusions: Circulating PCSK9 concentrations are associated with the metabolic complications of obesity, including insulin resistance, hyperglycaemia, hypertriglyceridemia and NASH and are not a direct reflect of its hepatic synthesis. ClinicalTrials.gov identifier : NCT00422006