Korczyńska Justyna, Czumaj Aleksandra, Chmielewski Michał, Śledziński Maciej, Mika Adriana, Śledziński Tomasz
Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Medical University of Gdansk, 80-211 Gdansk, Poland.
Department of Nephrology, Transplantology and Internal Medicine, Faculty of Medicine, Medical University of Gdansk, 80-211 Gdansk, Poland.
Metabolites. 2020 Mar 8;10(3):98. doi: 10.3390/metabo10030098.
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.
慢性肾脏病（CKD）与血清中瘦素水平升高及脂肪酸（FA）谱异常有关。然而，关于它们之间的关联尚无数据，且CKD患者血清水平升高的原因也未得到充分阐明。最近，我们发现与CKD相关的异常FA谱会导致肝细胞中参与脂质代谢的基因表达发生显著变化。本研究的目的是探讨CKD患者皮下脂肪组织（SAT）中的瘦素基因表达是否可能导致该脂肪因子血清水平升高，以及CKD患者中观察到的异常血清FA谱是否对脂肪细胞中的瘦素基因表达有影响。通过气相色谱 - 质谱联用（GC - MS）测定CKD患者和对照组血清样本中的FA谱。通过实时定量PCR测定SAT中瘦素的相对mRNA水平。此外，在体外培养的3T3 - L1脂肪细胞中研究了与CKD相关的异常FA谱对瘦素基因表达的影响。CKD患者的血清瘦素浓度高于对照组，且SAT中瘦素基因的表达水平更高。他们的血清单不饱和脂肪酸增加，多不饱和脂肪酸减少。用从CKD患者分离的脂肪酸孵育脂肪细胞导致瘦素mRNA水平升高。SAT中瘦素基因表达增加可能导致CKD患者中这些脂肪因子的浓度升高。CKD相关的FA谱改变可能通过增加SAT中该脂肪因子的基因表达，导致CKD患者血清瘦素浓度升高。
