Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets. - Archive ouverte HAL Access content directly
Journal Articles Nutrition and Metabolism Year : 2013

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

(1, 2) , (2) , (1, 2) , (3) , (3) , (3) , (2) , (2) , (1, 2) , (4) , (3) , (1, 2) , (3, 5) , (1, 2)
Cédric Langhi
  • Function : Author
  • PersonId : 935581
Murielle Bortolotti
  • Function : Author
  • PersonId : 935583
Kim-Anne Lê
  • Function : Author
  • PersonId : 935584
Fanny Theytaz
  • Function : Author
  • PersonId : 935585
Cédric Le May
Roland Kreis
  • Function : Author
  • PersonId : 935587
Chris Boesch
  • Function : Author
  • PersonId : 935588


ABSTRACT: BACKGROUND: 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. METHODS: 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 FINDINGS: 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. CONCLUSIONS: 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.
Fichier principal
Vignette du fichier
1743-7075-10-4.pdf (329.12 Ko) Télécharger le fichier
Vignette du fichier
1743-7075-10-4.xml (91.57 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Format : Other

Dates and versions

inserm-00778104 , version 1 (18-01-2013)



Bertrand Cariou, Cédric Langhi, Maëlle Le Bras, Murielle Bortolotti, Kim-Anne Lê, et al.. Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets.. Nutrition and Metabolism, 2013, 10 (1), pp.4. ⟨10.1186/1743-7075-10-4⟩. ⟨inserm-00778104⟩
103 View
162 Download



Gmail Facebook Twitter LinkedIn More