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

Abstract

Chronic kidney disease (CKD) is associated with an increased level of leptin and an abnormal fatty acid (FA) profile in the serum. However, there are no data on the associations between them, and the reason for increased serum levels in patients with CKD is not well elucidated. Recently, we found that a CKD-related abnormal FA profile caused significant changes in the expression of genes involved in lipid metabolism in hepatocytes. The aim of this study was to examine whether leptin gene expression in subcutaneous adipose tissue (SAT) of patients with CKD may contribute to increased serum levels of this adipokine and whether the abnormal serum FA profile observed in CKD patients has an impact on leptin gene expression in adipocytes. The FA profile was measured in serum samples from patients with CKD and controls by GC-MS. The relative mRNA levels of leptin were measured in SAT by Real-Time PCR. Moreover, the effect of the CKD-related abnormal FA profile on leptin gene expression was studied in in vitro cultured 3T3-L1 adipocytes. Patients with CKD had higher concentrations of serum leptin than controls and higher expression level of the leptin gene in SAT. They also had increased serum monounsaturated FAs and decreased polyunsaturated FAs. The incubation of adipocytes with FAs isolated from CKD patients resulted in an increase of the levels of leptin mRNA. Increased leptin gene expression in SAT may contribute to elevated concentrations of these adipokine in patients with CKD. CKD-related alterations of the FA profile may contribute to elevated serum leptin concentrations in patients with CKD by increasing the gene expression of this adipokine in SAT.

Increased adiponectin gene expression in adipose tissue may be related to an abnormal serum fatty acid profile in patients with chronic kidney disease

“…A research scheme showing the recruitment of study subjects and collection of biological material from them is presented as a supplementary Figure S1. The characteristics of these patients had been reported previously [2,8]. Blood samples were taken after overnight fasting from all the study subjects.…”

“…FA profiles were analyzed by gas chromatography-mass spectrometry (GC-MS) using QP-2010SE apparatus (Shimadzu, Kyoto, Japan), as described previously [2,8].…”

“…Cells were supplemented with one of the following FA for 48h: palmitic acid (PAL, 16:0), oleic acid (OA, 18:1), docosahexaenoic acid (DHA, 22:6 n-3) and arachidonic acid (AA, 20:4 n-6) in three different concentrations (25µM, 50µM, and 100µM). Moreover, 3T3L1 adipocytes were supplemented with FA mix pooled from the FA isolated from serum of CKD stage 5 patients and healthy controls -from randomly selected patients and control serum samples, total lipids were extracted and hydrolyzed as we described previously [2,5].…”

“…Chronic kidney disease (CKD) is associated with increased serum leptin and adiponectin concentrations, that may contribute to CKD progression and the risk of comorbidities [1]. Our previous study showed that in patients with CKD, increased leptin gene expression in subcutaneous adipose tissue (SAT) contributes to elevated concentrations of this adipokine [2].…”

“…Moreover, CKD-related alterations of the fatty acid (FA) profile play a role in elevating serum leptin concentrations in patients with CKD by increasing the gene expression of this adipokine in adipocytes [2]. Adiponectin is another abundant adipocyte-derived hormone with a wide range of biological activities.…”