Alterations of Fatty Acid Profile May Contribute to Dyslipidemia in Chronic Kidney Disease by Influencing Hepatocyte Metabolism

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.

Increased Expression of the Leptin Gene in Adipose Tissue of Patients with Chronic Kidney Disease–The Possible Role of an Abnormal Serum Fatty Acid Profile

“…A mixture of fatty acids isolated from the patients and controls sera was added to the cell culture at exactly the same concentration as in the study participants' sera. The FA set isolated from the serum of patients with CKD was characterized by a higher content of MUFAs and SFAs and a lower content of n-3 and n-6 PUFAs than FAs isolated from serum of control subjects [16].…”

“…It is still unclear whether changes in leptin levels in CKD are caused by a reduced glomerular filtration rate, increased production in adipose tissue, or both. Our previous study showed that an altered FA profile in patients with CKD significantly changed hepatocyte metabolism [16]. Thus, in the present study, we aimed to examine the associations of leptin serum levels and its gene expression in adipose tissue.…”

“…After 1.5 h, 1 mL of water was added to the mixture, and FAMEs were extracted three times with 1 mL of n-hexane and dried under nitrogen stream. Fatty acid profiles were analyzed by gas chromatography-mass spectrometry (GC-MS), using a QP-2010SE apparatus (Shimadzu, Kyoto, Japan), as described previously [16]. In brief, a 30 m 0.25 mm i.d.…”

“…Cells were supplemented for 48 h, with one selected fatty acid: PA, OA, DHA, and AA or with the full FA set isolated from pooled serum of 10 randomly selected patients with stage 5 CKD, or 10 healthy controls. From pooled patient or control serum samples, total lipids were extracted and hydrolyzed, as previously described in Czumaj et al (2019) [16]. A mixture of fatty acids isolated from the patients and controls sera was added to the cell culture at exactly the same concentration as in the study participants' sera.…”

“…The most frequently described changes focus on cholesterol and triacylglycerols. Many studies, including our previous research, have also shown abnormal serum fatty acid (FA) profiles in patients with CKD [16][17][18]. Dyslipidemia observed in patients with CKD is one of the well-known risk factors of cardiovascular disease (CVD) or diabetes mellitus [19][20][21].…”