C Blanchard1, S Ledoux2, A Verhaegen3, M Wargny4, E Letessier5, A Stepanian6, N Huten7, D Jacobi8, M Krempf9, M Le Bras10, M Perrocheau Guillouche10, L Arnaud11, M Pichelin4, L Van Gaal3, B Cariou4, C Le May12. 1. University of Nantes, CNRS, Inserm, Thorax Institute, 44000 Nantes, France; Clinical Department of Digestive and Endocrine Surgery, CHU of Nantes, Nantes, France. 2. Department of Functional Explorations, North Francilien Integrated Obesity Centre (CINFO), Hôpital Louis Mourier (AP-HP.7), University of Paris, Paris, France. 3. Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium. 4. University of Nantes, CNRS, Inserm, Thorax Institute, 44000 Nantes, France; Thorax Institute, Department of Endocrinology, CIC 1413 Inserm, CHU Nantes, Nantes, France. 5. Clinical Department of Digestive and Endocrine Surgery, CHU of Nantes, Nantes, France. 6. AP-HP, Hôpital Lariboisière, Department of Biological Haematology, Paris, France. 7. Digestive, Endocrine, Oncology and Liver Transplantation Department, CHU of Tours, Tours, France. 8. University of Nantes, CNRS, Inserm, Thorax Institute, 44000 Nantes, France; Digestive, Endocrine, Oncology and Liver Transplantation Department, CHU of Tours, Tours, France. 9. Thorax Institute, Department of Endocrinology, CIC 1413 Inserm, CHU Nantes, Nantes, France; INRA, UMR 1280, Physiology of Nutritional Adaptations, CHU Hôtel-Dieu, 44000 Nantes, France. 10. Thorax Institute, Department of Endocrinology, CIC 1413 Inserm, CHU Nantes, Nantes, France. 11. University of Nantes, CNRS, Inserm, Thorax Institute, 44000 Nantes, France. 12. University of Nantes, CNRS, Inserm, Thorax Institute, 44000 Nantes, France. Electronic address: cedric.lemay@univ-nantes.fr.
Abstract
AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a master regulator of low-density lipoprotein cholesterol (LDL-C) metabolism, acting as an endogenous inhibitor of the LDL receptor. While it has been shown that bariatric surgery differentially affects plasma LDL-C levels, little is known of its effects on plasma PCSK9 concentrations. Therefore, the present study aimed to: (i) investigate the effect of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on plasma PCSK9 concentrations; and (ii) correlate baseline or postoperative plasma PCSK9 concentration variations with anthropometric and metabolic parameters. METHODS: Fasting plasma PCSK9 levels were measured by ELISA in morbidly obese patients before and 6 months after bariatric surgery. Patients were recruited from three prospective cohorts (in Nantes and Colombes in France, and Antwerp in Belgium). RESULTS: A total of 156 patients (34SG, 122RYGB) were included. Plasma PCSK9, LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) levels were significantly reduced after RYGB (-19.6%, -16.6% and -19.5%, respectively; P<0.0001), but not after SG. In all patients, postoperative PCSK9 change was positively correlated with fasting plasma glucose (FPG; r=0.22, P=0.007), HOMA-IR (r=0.24, P=0.005), total cholesterol (r=0.17, P=0.037) and non-HDL-C (r=0.17, P=0.038) variations, but not LDL-C. In contrast to what was observed for glucose parameters (FPG, HOMA-IR), correlation between PCSK9 and non-HDL-C changes after RYGB was independent of total weight loss. CONCLUSION: RYGB, but not SG, promotes a significant reduction in plasma PCSK9 levels, and such changes in circulating PCSK9 levels after RYGB appear to be more associated with glucose improvement than with lipid homoeostasis parameters.
AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a master regulator of low-density lipoprotein cholesterol (LDL-C) metabolism, acting as an endogenous inhibitor of the LDL receptor. While it has been shown that bariatric surgery differentially affects plasma LDL-C levels, little is known of its effects on plasma PCSK9 concentrations. Therefore, the present study aimed to: (i) investigate the effect of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on plasma PCSK9 concentrations; and (ii) correlate baseline or postoperative plasma PCSK9 concentration variations with anthropometric and metabolic parameters. METHODS: Fasting plasma PCSK9 levels were measured by ELISA in morbidly obesepatients before and 6 months after bariatric surgery. Patients were recruited from three prospective cohorts (in Nantes and Colombes in France, and Antwerp in Belgium). RESULTS: A total of 156 patients (34SG, 122RYGB) were included. Plasma PCSK9, LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) levels were significantly reduced after RYGB (-19.6%, -16.6% and -19.5%, respectively; P<0.0001), but not after SG. In all patients, postoperative PCSK9 change was positively correlated with fasting plasma glucose (FPG; r=0.22, P=0.007), HOMA-IR (r=0.24, P=0.005), total cholesterol (r=0.17, P=0.037) and non-HDL-C (r=0.17, P=0.038) variations, but not LDL-C. In contrast to what was observed for glucose parameters (FPG, HOMA-IR), correlation between PCSK9 and non-HDL-C changes after RYGB was independent of total weight loss. CONCLUSION: RYGB, but not SG, promotes a significant reduction in plasma PCSK9 levels, and such changes in circulating PCSK9 levels after RYGB appear to be more associated with glucose improvement than with lipid homoeostasis parameters.
Authors: C Macchi; C Favero; A Ceresa; L Vigna; D M Conti; A C Pesatori; G Racagni; A Corsini; N Ferri; C R Sirtori; M Buoli; V Bollati; M Ruscica Journal: Cardiovasc Diabetol Date: 2020-11-03 Impact factor: 8.949