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
AbstractChronic 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.
|Journal series||International Journal of Molecular Sciences, ISSN 1422-0067, (N/A 100 pkt)|
|Publication size in sheets||0.65|
|Keywords in English||chronic kidney disease, fatty acids, lipids, lipogenesis, hypertriglyceridemia, hepatocyte|
|ASJC Classification||; ; ; ; ; ; ;|
|License||Journal (articles only); published final; ; with publication|
|Score||= 100.0, 06-12-2019, ArticleFromJournal|
|Publication indicators||= 0; = 0; : 2018 = 1.224; : 2018 = 4.183 (2) - 2018=4.331 (5)|
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