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

• Published in: Nutrition, metabolism, and cardiovascular diseases metabolism, and cardiovascular diseases, 2020-11, Vol.30 (12), p.2372-2378
• Main Authors: Zenti, Maria G., Lupo, Maria G., De Martin, Sara, Altomari, Anna, Galvan, Serena, Aventaggiato, Marta, Maneschi, Chiara, Sandri, Damiano, Paiola, Elena, Battistoni, Marco, Eccher, Albino, Targher, Giovanni, Bonora, Enzo, Ruscica, Massimiliano, Ferri, Nicola
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adult; Bariatric; Biomarkers - blood; Blood Glucose - metabolism; Body Mass Index; Case-Control Studies; Female; Gastrectomy; Gastric Bypass; Glucose; Glucose Tolerance Test; Humans; Insulin - blood; Insulin Resistance; Male; Middle Aged; Obesity - blood; Obesity - diagnosis; Obesity - physiopathology; Obesity - surgery; OGTT; PCSK9; Pilot Projects; Proprotein Convertase 9 - blood; Time Factors; Treatment Outcome; Weight Loss; Young Adult
• ISSN: 0939-4753; 1590-3729
• DOI: 10.1016/j.numecd.2020.07.013

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. In this non-randomized interventional study, we enrolled 36 severely obese patients (BMI 43.7 ± 5.6 kg/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-h hyperinsulinemic-euglycemic clamp (HEC). At T0, PCSK9 levels were higher in obese patients than in controls (274.6 ± 76.7 ng/mL vs. 201.4 ± 53.3 ng/mL) and dropped after bariatric surgery (T6; 205.5 ± 51.7 ng/mL) along with BMI (from 44.1 ± 5.9 kg/m2 to 33.1 ± 5.6 kg/m2). At T6, there was also a decrease in plasma glucose (T0 vs. T6: 6.0 ± 1.8 vs. 5.0 ± 0.5 mmol/L) and insulin (15.7 ± 8.3 vs. 5.4 ± 2.1 mU/L) levels. At T0, plasma PCSK9 levels decreased during OGTT in obese patients, reaching a nadir of 262.0 ± 61.4 ng/mL at 120 min with a hyperinsulinemic peak of 75.1 ± 40.0 mU/L, at 60 min. Similarly, at T0 insulin infusion during 2-h HEC 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. These results suggest a pivotal role of adipose tissue and insulin resistance on PCSK9 homeostasis in severely obese patients. •Severely obese patients have higher plasma PCSK9 levels than nonobese control subjects.•Bariatric surgery-induced weight loss markedly improved insulin resistance and normalized plasma PCSK9 levels.•PCSK9 plasma levels decline both during OGTT and HEC.•Adipose tissue and associated insulin resistance plays a role on PCSK9 clearance and/or turnover.