Document Type

Article

Publication Date

1-7-2022

Publication Title

Lab Anim Res

Keywords

JMG

JAX Source

Lab Anim Res 2022 Jan 7; 38(1):1

Volume

38

Issue

1

First Page

1

Last Page

1

ISSN

1738-6055

PMID

34996527

DOI

https://doi.org/10.1186/s42826-021-00111-2

Grant

HL077796, HL095668

Abstract

BACKGROUND: The convertase subtilisin/kexin family 1 gene (PCSK1) has been associated in various human genetics studies with a wide spectrum of metabolic phenotypes, including early-onset obesity, hyperphagia, diabetes insipidus, and others. Despite the evident influence of PCSK1 on obesity and the known functions of other PCSKs in lipid metabolism, the role of PCSK1 specifically in lipid and cholesterol metabolism remains unclear. This study evaluated the effect of loss of PCSK1 function on high-density lipoprotein (HDL) metabolism in mice.

RESULTS: HDL cholesterol, apolipoprotein A1 (APOA1) levels in serum and liver, and the activities of two enzymes (lecithin-cholesterol acyltransferase, LCAT and phospholipid transfer protein, PLTP) were evaluated in 8-week-old mice with a non-synonymous single nucleotide mutation leading to an amino acid substitution in PCSK1, which results in a loss of protein's function. Mutant mice had similar serum HDL cholesterol concentration but increased levels of serum total and mature APOA1, and LCAT activity in comparison to controls.

CONCLUSIONS: This study presents the first evaluation of the role of PCSK1 in HDL metabolism using a loss-of-function mutant mouse model. Further investigations will be needed to determine the underlying molecular mechanism.

Comments

In memory of Beverly Paigen (1938-2020). We thank Joanne Currer for editorial advice; Kyle Beauchemin, George Sutphin, Christopher McCarty, and Elisabeth Adkins for scientific discussion and feedback; Beverly Macy and Rachel Gott for animal care and serum collection; Sue Grindle for HDL cholesterol measurement; Susan Sheehan and Kenneth Walsh for general technical support.

Open Access This article is licensed under a Creative Commons
Attribution 4.0 International License.

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