Effect of Restricted Caloric Intake and Bariatric Surgery on PCSK9 Concentrations in Plasma

PCSK9 is a major modulator of LDLc through internalization and endosomal degradation of LDL receptor. It has been shown that PCSK9 plasma levels predict CVD risk. Bariatric surgery is known to reduce both LDLc and CVD. However, its exact effect on circulating PCSK9 levels has not been fully investigated. We have now investigated the effect of strict caloric restriction and Roux-en-Y bariatric surgery (RYGB) in 15 morbidly obese patients on plasma PCSK-9 levels. Subjects were instructed to follow a regimen of 4 liquid shakes (up to 16g carbohydrate, 0g fat, and 33g of protein, total daily intake was 550-785 calories) during the 2-weeks strict caloric restriction period prior to surgery and the usual dietary regime after surgery. Blood samples were obtained at 2 weeks before, at the time of surgery and 6 months after RYGB. There was a significant weight loss of 7.8±2.4 Kg during the 2 weeks prior to surgery and of additional 26.6±5.3 Kg 6 months after surgery. At completion of strict caloric restriction, subjects had a significant reductions in glucose, insulin and HOMA-IR (7.1±1.1 to 4.5± 1.0) which continued following surgery (HOMA-IR (4.5±1.0 to 2.1± 0.3). LDL(c) fell significantly by 11±7% (from 120±6 to 109±7mg/dl) following the strict caloric restriction and by 15±8% (from 109±7 to 95±6mg/dl) following surgery. There was a reduction of 38±11% (from 227±25 to 139±15 ng/ml) in plasma PCSK9 concentration in the 2 weeks of caloric restriction. Thereafter, PCSK9 levels increased to 166±22ng/ml over the next 6 months. Our data show that there is an impressive and concurrent fall in PCSK9, LDL(c) concentrations and insulin resistance following strict caloric restriction. The marked weight loss over 6 months has only a marginal effect on PCSK9 concentrations while metabolic improvements persisted. This reduction in PCSK9 may contribute to the known benefit in cardiovascular outcomes following bariatric surgery.