Alterations of fatty acid profile may contribute to dyslipidemia in chronic kidney disease by influencing hepatocyte metabolism

Aleksandra Czumaj , Tomasz Śledziński , Juan-Jesus Carrero , Piotr Stepnowski , Malgorzata Sikorska-Wisniewska , Michał Chmielewski , Adriana Mika

Abstract

Chronic kidney disease (CKD) is associated with atherogenic dyslipidemia. Our aim was firstly to investigate patterns of fatty acids (FA) composition through various stages of CKD, and secondly, to evaluate the effect of CKD-specific FA disturbances on the expression of genes related to lipid metabolism at a cellular level. Serum FA composition was analyzed in 191 patients with consecutive severity stages of CKD, and 30 healthy controls free from CKD. Next, HepG2 human hepatic cells were treated with major representatives of various FA groups, as well as with FA extracted from a mix of serums of controls and of CKD stage 5 patients. Across worsening stages of CKD severity, there was an increasing monounsaturated FA (MUFA) content. It was associated with a concomitant decrease in n-3 and n-6 polyunsaturated FA. The incubation of hepatocytes with FA from CKD patients (compared to that of healthy subjects), resulted in significantly higher mRNA levels of genes involved in FA synthesis (fatty acid synthase (FASN) increased 13.7 ± 3.5 times, stearoyl-CoA desaturase 1 (SCD1) increased 4.26 ± 0.36 times), and very low density lipoprotein (VLDL) formation (apolipoprotein B (ApoB) increased 7.35 ± 1.5 times, microsomal triacylglycerol transfer protein (MTTP) increased 2.74 ± 0.43 times). In conclusion, there were progressive alterations in serum FA composition of patients with CKD. These alterations may partly contribute to CKD hypertriglyceridemia by influencing hepatocyte expression of genes of lipid synthesis and release.
Author Aleksandra Czumaj - [Gdanski Uniwersytet Medyczny]
Aleksandra Czumaj,,
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- Gdanski Uniwersytet Medyczny
, Tomasz Śledziński - [Gdanski Uniwersytet Medyczny]
Tomasz Śledziński,,
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- Gdanski Uniwersytet Medyczny
, Juan-Jesus Carrero - [Karolinska Institutet]
Juan-Jesus Carrero,,
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, Piotr Stepnowski (FCh / DEA / LChER)
Piotr Stepnowski,,
- Laboratory of Chemical Environmental Risks
, Malgorzata Sikorska-Wisniewska - [Gdanski Uniwersytet Medyczny]
Malgorzata Sikorska-Wisniewska,,
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- Gdanski Uniwersytet Medyczny
, Michał Chmielewski - [Gdanski Uniwersytet Medyczny]
Michał Chmielewski,,
-
- Gdanski Uniwersytet Medyczny
, Adriana Mika (FCh / DEA / LChER)
Adriana Mika,,
- Laboratory of Chemical Environmental Risks
Journal seriesInternational Journal of Molecular Sciences, ISSN 1422-0067, (N/A 100 pkt)
Issue year2019
Vol20
No10
Pages1-14
Publication size in sheets0.65
Article number2470
Keywords in Englishchronic kidney disease, fatty acids, lipids, lipogenesis, hypertriglyceridemia, hepatocyte
ASJC Classification2700 General Medicine; 1312 Molecular Biology; 1503 Catalysis; 1604 Inorganic Chemistry; 1605 Organic Chemistry; 1606 Physical and Theoretical Chemistry; 1607 Spectroscopy; 1706 Computer Science Applications
DOIDOI:10.3390/ijms20102470
URL https://doi.org/10.3390/ijms20102470
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)100
Score sourcejournalList
ScoreMinisterial score = 100.0, 06-12-2019, ArticleFromJournal
Publication indicators WoS Citations = 0; Scopus Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.224; WoS Impact Factor: 2018 = 4.183 (2) - 2018=4.331 (5)
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