Article

PDF
Access to the PDF text
Advertising


Free Article !

Archives of cardiovascular diseases
Volume 102, n° S1
pages 20-21 (mars 2009)
Doi : 10.1016/S1875-2136(09)72172-2
B001 PCSK9 deficient mice are not protected against hypercholesterolemia when fed a high fat diet
 

C. Le May 1, B. Cariou 1, P. Costet 1
1 Inserm U915, Nantes, France 

B — DIABETE, LIPIDES, METABOLISME

@@#100979@@
Introduction

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a natural inhibitor of the low density lipoprotein receptor (LDLr) and its deficiency confers a high protection against cardiovascular diseases. We previously reported that PCSK9 expression is regulated by nutritional status and insulinemia.

Objectives

Here, we investigated the metabolic adaptation of PCSK9 deficient mice (PCSK9-/-) in response to a high fat diet (HFD).

Methods & Results

PCSK9-/- and PCSK9+/+ males were given a 60 % fat diet for 10 weeks. Before treatment, both genotypes responded similarly to oral glucose tolerance (OGTT) and insulin tolerance test (ITT). The first week following HFD feeding, we noticed an initial rise in glycemia for both genotypes (32 and 37.8 %), reflecting diet-induced insulin resistance. Despite comparable OGTT and ITT, PCSK9-/- mice presented a slight reduction of blood glucose compared to PCSK9+/+ littermates during the all period of HFD feeding. By contrast, PCSK9 deficiency did not alter body weight, plasma triglyceride or free fatty acids levels in response to HFD. On regular diet, PCSK9-/- mice have significant reduction of circulating cholesterol compared to PCSK9+/+ mice (0.721±0.05 g/l vs 1.06±0.04 P=0.0002). Surprisingly, after one week of diet, this phenotype was lost and cholesterol levels were not significantly different between PCSK9-/- and PCSK9+/+ mice (respectively: 1.327±0.07 g/l vs 1.501±0.05 P=0.065).

Conclusions

Here, we demonstrated that under HFD, PCSK9 deficiency did not affect weight gain, insulin sensitivity or plasma triglyceride levels. However, the absence of PCSK9 didn’t prevent hypercholesterolemia, suggesting a cross talk between PCSK9- mediated LDLr degradation and the molecular pathways affected by a dietary fat excess.

The full text of this article is available in PDF format.
The full text of this article is available in PDF format.
Click here to see it.


© 2009  Elsevier Masson SAS. All Rights Reserved.
EM-CONSULTE.COM is registrered at the CNIL, déclaration n° 1286925.
As per the Law relating to information storage and personal integrity, you have the right to oppose (art 26 of that law), access (art 34 of that law) and rectify (art 36 of that law) your personal data. You may thus request that your data, should it be inaccurate, incomplete, unclear, outdated, not be used or stored, be corrected, clarified, updated or deleted.
Personal information regarding our website's visitors, including their identity, is confidential.
The owners of this website hereby guarantee to respect the legal confidentiality conditions, applicable in France, and not to disclose this data to third parties.
Close
Article Outline
You can move this window by clicking on the headline
@@#110903@@