Open Access Open Badges Research

Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets

Bertrand Cariou123*, Cédric Langhi1, Maëlle Le Bras13, Murielle Bortolotti4, Kim-Anne Lê4, Fanny Theytaz4, Cédric Le May1, Béatrice Guyomarc’h-Delasalle1, Yassine Zaïr13, Roland Kreis5, Chris Boesch5, Michel Krempf123, Luc Tappy46 and Philippe Costet137*

Author Affiliations

1 INSERM, UMR 1087, F-44000, Nantes, France

2 Université de Nantes, Faculté de Médecine, Institut du Thorax, F-44000, Nantes, France

3 CHU de Nantes, Clinique d'Endocrinologie, Institut du Thorax, F-44000, Nantes, France

4 Department of Physiology, University of Lausanne, Lausanne, Switzerland

5 Department of Clinical research, MR Spectroscopy and Methodology, University of Bern, Bern, Switzerland

6 Division of Diabetes, Endocrinology and Metabolism, Lausanne University Hospital, Lausanne, Switzerland

7 Present address: SUNY Downstate Medical Center, Department of Cell Biology, 450 Clarkson Avenue, 11203, New York, NY, USA

For all author emails, please log on.

Nutrition & Metabolism 2013, 10:4  doi:10.1186/1743-7075-10-4

Published: 8 January 2013



PCSK9 (Proprotein Convertase Subtilisin Kexin type 9) is a circulating protein that promotes hypercholesterolemia by decreasing hepatic LDL receptor protein. Under non interventional conditions, its expression is driven by sterol response element binding protein 2 (SREBP2) and follows a diurnal rhythm synchronous with cholesterol synthesis. Plasma PCSK9 is associated to LDL-C and to a lesser extent plasma triglycerides and insulin resistance. We aimed to verify the effect on plasma PCSK9 concentrations of dietary interventions that affect these parameters.


We performed nutritional interventions in young healthy male volunteers and offspring of type 2 diabetic (OffT2D) patients that are more prone to develop insulin resistance, including: i) acute post-prandial hyperlipidemic challenge (n=10), ii) 4 days of high-fat (HF) or high-fat/high-protein (HFHP) (n=10), iii) 7 (HFruc1, n=16) or 6 (HFruc2, n=9) days of hypercaloric high-fructose diets. An acute oral fat load was also performed in two patients bearing the R104C-V114A loss-of-function (LOF) PCSK9 mutation. Plasma PCSK9 concentrations were measured by ELISA. For the HFruc1 study, intrahepatocellular (IHCL) and intramyocellular lipids were measured by 1H magnetic resonance spectroscopy. Hepatic and whole-body insulin sensitivity was assessed with a two-step hyperinsulinemic-euglycemic clamp (0.3 and 1.0


HF and HFHP short-term diets, as well as an acute hyperlipidemic oral load, did not significantly change PCSK9 concentrations. In addition, post-prandial plasma triglyceride excursion was not altered in two carriers of PCSK9 LOF mutation compared with non carriers. In contrast, hypercaloric 7-day HFruc1 diet increased plasma PCSK9 concentrations by 28% (p=0.05) in healthy volunteers and by 34% (p=0.001) in OffT2D patients. In another independent study, 6-day HFruc2 diet increased plasma PCSK9 levels by 93% (p<0.0001) in young healthy male volunteers. Spearman’s correlations revealed that plasma PCSK9 concentrations upon 7-day HFruc1 diet were positively associated with plasma triglycerides (r=0.54, p=0.01) and IHCL (r=0.56, p=0.001), and inversely correlated with hepatic (r=0.54, p=0.014) and whole-body (r=−0.59, p=0.0065) insulin sensitivity.


Plasma PCSK9 concentrations vary minimally in response to a short term high-fat diet and they are not accompanied with changes in cholesterolemia upon high-fructose diet. Short-term high-fructose intake increased plasma PCSK9 levels, independent on cholesterol synthesis, suggesting a regulation independent of SREBP-2. Upon this diet, PCSK9 is associated with insulin resistance, hepatic steatosis and plasma triglycerides.

Nutrition; Dietary intervention; PCSK9; Insulin resistance; Liver steatosis