Background Proprotein convertase subtilisin kexin type 9 (PCSK9) regulates low-density lipoprotein and very low-density lipoprotein receptor expression in several tissues. Here we evaluated whether PCSK9 may modulate the handling of triglycerides in the liver and peripheral tissues. Methods Subjects from the PLIC cohort were genotyped for the loss-of-function PCSK9 R46L variant and characterized for clinical and biochemical parameters, total and android fat mass, hepatic steatosis and epicardial fat thickness. Visceral adipose tissue and subcutaneous adipose tissue in PCSK9 KO and wild type mice were quantified by nuclear magnetic resonance imaging. Results Carriers of the R46L variant ( n = 13) had lower low-density lipoprotein cholesterol levels, higher body mass index and increased percentage of total and android fat masses compared with non-carriers ( n = 521). R46L variant associated with a two-fold increase prevalence of hepatic steatosis and higher epicardial fat thickness. These observations were replicated in PCSK9 KO mice, which showed increased visceral adipose tissue (but not subcutaneous adipose tissue) when fed chow or high-fat diet for 20 weeks, compared with wild type mice. Conclusions These data suggest that genetically determined PCSK9 deficiency might be associated with ectopic fat accumulation.

PCSK9 deficiency results in increased ectopic fat accumulation in experimental models and in humans / A. Baragetti, G. Balzarotti, L. Grigore, F. Pellegatta, U. Guerrini, G. Pisano, A.L. Fracanzani, S. Fargion, G.D. Norata, A.L. Catapano. - In: EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY. - ISSN 2047-4873. - 24:17(2017 Nov), pp. 1870-1877. [10.1177/2047487317724342]

PCSK9 deficiency results in increased ectopic fat accumulation in experimental models and in humans

A. Baragetti;G. Balzarotti;F. Pellegatta;U. Guerrini;G. Pisano;A.L. Fracanzani;S. Fargion;G.D. Norata;A.L. Catapano
2017-11

Abstract

Background Proprotein convertase subtilisin kexin type 9 (PCSK9) regulates low-density lipoprotein and very low-density lipoprotein receptor expression in several tissues. Here we evaluated whether PCSK9 may modulate the handling of triglycerides in the liver and peripheral tissues. Methods Subjects from the PLIC cohort were genotyped for the loss-of-function PCSK9 R46L variant and characterized for clinical and biochemical parameters, total and android fat mass, hepatic steatosis and epicardial fat thickness. Visceral adipose tissue and subcutaneous adipose tissue in PCSK9 KO and wild type mice were quantified by nuclear magnetic resonance imaging. Results Carriers of the R46L variant ( n = 13) had lower low-density lipoprotein cholesterol levels, higher body mass index and increased percentage of total and android fat masses compared with non-carriers ( n = 521). R46L variant associated with a two-fold increase prevalence of hepatic steatosis and higher epicardial fat thickness. These observations were replicated in PCSK9 KO mice, which showed increased visceral adipose tissue (but not subcutaneous adipose tissue) when fed chow or high-fat diet for 20 weeks, compared with wild type mice. Conclusions These data suggest that genetically determined PCSK9 deficiency might be associated with ectopic fat accumulation.
PCSK9; ectopic fat; loss of function mutations
Settore BIO/14 - Farmacologia
Settore MED/09 - Medicina Interna
Article (author)
File in questo prodotto:
File Dimensione Formato  
2047487317724342.pdf

non disponibili

Tipologia: Publisher's version/PDF
Dimensione 342.07 kB
Formato Adobe PDF
342.07 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
2047487317724342-1.pdf

non disponibili

Tipologia: Publisher's version/PDF
Dimensione 366.97 kB
Formato Adobe PDF
366.97 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/527125
Citazioni
  • ???jsp.display-item.citation.pmc??? 10
  • Scopus 34
  • ???jsp.display-item.citation.isi??? 35
social impact