Abstract
ObjectivesTo investigate the serum, plasma and urine levels of lipocalin-2 (LCN2) variants in healthy humans and their associations with risk factors for cardiometabolic (CMD) and chronic kidney (CKD) diseases.MethodsFifty-nine males and 41 females participated in the study. Blood and urine were collected following an overnight fasting. LCN2 variants were analyzed using validated in-house ELISA kits. Heart rate, blood pressure, lipids profile, glucose, adiponectin, high-sensitivity C-reactive protein (hsCRP), creatinine, cystatin C, and biomarkers for kidney function were assessed.ResultsThe levels of hLcn2, C87A and R81E in serum and urine, but not plasma, were significantly higher in men than women. Increased levels of LCN2 variants, as well as their relative ratios, in serum and plasma were positively associated with body mass index, blood pressure, triglyceride and hsCRP (P<0.05). No significant correlations were found between these measures and hLcn2, C87A or R81E in urine. However, LCN2 variants in urine, but not plasma or serum, were correlated with biomarkers of kidney function (P<0.05).ConclusionsBoth the serum and plasma levels of LCN2 variants, as well as their ratios are associated with increased cardiometabolic risk, whereas those in urine are correlated with renal dysfunction. LCN2 variants represent promising biomarkers for CMD and CKD.
Highlights
Emerging research reveals a complex and actively regulated crosstalk between bone, muscle and adipose tissue, which is implicated in metabolic and cardiovascular regulation [1]
Lipocalin-2 (LCN2), known as neutrophil gelatinaseassociated lipocalin (NGAL), super inducible protein 24 (SIP24), 24p3/uterocalin, or a2-microglobulin-related protein/ neu-related lipocalin, is a member of the lipocalin protein family characterized by highly diversified patterns of expression and structure-function relationships [2]
Plasma and urine levels of LCN2 have been regarded as biomarkers for cardiometabolic (CMD) and chronic kidney (CKD) diseases [4, 8,9,10,11], there are inconsistent reports on the use of this molecule as a biomarker for early diagnosis or prognosis [8, 12, 13]
Summary
Emerging research reveals a complex and actively regulated crosstalk between bone, muscle and adipose tissue, which is implicated in metabolic and cardiovascular regulation [1]. LCN2 is expressed and released from various cell types [3], and may represent a specific hormone involved in the interactions between bone, muscle and adipose tissue [1]. The pathological forms of adipose-derived LCN2 play a causal role in obesityassociated cardiometabolic and renal diseases [6, 7]. Different LCN2 variants are distinctively present in samples from healthy humans and patients with cardiometabolic abnormalities [4, 14, 15], and play diversified roles in causing cardiovascular, renal and metabolic abnormalities [14,15,16,17,18]. The vast majority of previous research focus on total LCN2 levels
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