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.

The hormone erythropoietin stimulates erythrocyte production and therefore regulates the oxygen capacity of the blood. Hypoxia promotes erythropoietin formation by stimulating the transcription of the erythropoietin gene in the kidney and, to a lesser extent, in the liver. Chemical signals involved in the activation of the erythropoietin gene seem to be prostaglandins and cyclic AMP. The cells that serve as oxygen sensors may be mesangial cells of the glomerulus;in culture these cells release erythropoietin when oxygen tension is lowered.

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Osteoglycin (OGN) is a leucine-rich proteoglycan that has been implicated in the regulation of glucose in animal models. However, its relationship with glucose control in humans is unclear. We examined the effect of high-intensity interval exercise (HIIE) and hyperinsulinemic-euglycemic clamp on circulating levels of OGN as well as whether circulating OGN levels are associated with markers of glycemic control and cardio-metabolic health. Serum was analyzed for OGN (ELISA) levels from 9 middle-aged obese men (58.1 AE 2.2 years, body mass index [BMI] = 33.1 AE 1.4 kgÁm À2 , mean AE SEM) and 9 young men (27.8 AE 1.6 years, BMI = 24.4 AE 0.08 kgÁm À2 ) who previously completed a study involving a euglycemic-hyperinsulinemic clamp at rest and after HIIE (4x4 minutes cycling at approximately 95% peak heart rate (HRpeak), interspersed with 2 minutes of active recovery). Blood pressure, body composition (dual-energy X-ray absorptiometry), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) were assessed. Serum OGN was higher in the young cohort compared with the middle-aged cohort (65.2 AE 10.1 ng/mL versus 36.5 AE 4. 5 ng/mL, p ≤ 0.05). Serum OGN was unaffected by acute HIIE but decreased after the insulin clamp compared with baseline (~À27%, p = 0.01), post-exercise (~À35%, p = 0.01), and pre-clamp (~À32%, p = 0.02) time points, irrespective of age. At baseline, lower circulating OGN levels were associated with increased age, BMI, and fat mass, whereas higher OGN levels were related to lower fasting glucose. Higher OGN levels were associated with a higher glucose infusion rate. Exercise had a limited effect on circulating OGN. The mechanisms by which OGN affects glucose regulation should be explored in the future.