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.
Highlights
Chronic kidney disease (CKD) is accompanied by lipid disorders due to metabolic alterations associated with the retention of uremic solutes, as well as to dietary restrictions and impaired food intake resulting from chronic intoxication [1]
Following a multivariable general linear model (GLM) analysis, CKD stage emerged as a significant predictor of monounsaturated FA (MUFA) and polyunsaturated fatty acids (PUFA) proportions
We show that across worsening stages of CKD severity, there was an increasing MUFA and gradually decreasing n-3 and n-6 PUFA content
Summary
Chronic kidney disease (CKD) is accompanied by lipid disorders due to metabolic alterations associated with the retention of uremic solutes, as well as to dietary restrictions and impaired food intake resulting from chronic intoxication [1]. Dialysis does not normalize the lipid profile, and in patients after renal transplantation it may even further aggravate, mainly because of the immunosuppressive treatment. Lipids count over 1.6 million species and most of them contain fatty acids (FA) in their structure [2]. Disturbed blood FA profile is associated with oxidative stress, lipotoxicity and hypertriglyceridemia. Patients suffering from CKD are potentially prone to FA disorders due to metabolic alterations associated with the retention of uremic solutes, as well as to dietary restrictions and impaired food intake resulting from chronic intoxication
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