Zinc alpha 2 glycoprotein as an early biomarker of diabetic nephropathy in patients with type 2 diabetes mellitus.

INTRODUCTION: Although microalbuminuria remains the gold standard for early detection of diabetic nephropathy (DN), it is not a sufficiently accurate predictor of DN risk. Thus, new biomarkers that would help to predict DN risk earlier and possibly prevent the occurrence of end-stage kidney disease are being investigated. OBJECTIVE: To investigate the role of zinc-alpha-2-glycoprotein (ZAG) as an early marker of DN in type 2 diabetic (T2DM) patients. METHODS: 88 persons were included and classified into 4 groups: Control group (group I), composed of normal healthy volunteers, and three patient groups with type 2 diabetes mellitus divided into: normo-albuminuria group (group II), subdivided into normal eGFR subgroup and increased eGFR subgroup > 120 mL/min/1.73m2), microalbuminuria group (group III), and macroalbuminuria group (group IV). All subjects were submitted to urine analysis, blood glucose levels, HbA1c, liver function tests, serum creatinine, uric acid, lipid profile and calculation of eGFR, urinary albumin creatinine ratio (UACR), and measurement of urinary and serum ZAG. RESULTS: The levels of serum and urine ZAG were higher in patients with T2DM compared to control subjects and a statistically significant difference among studied groups regarding serum and urinary ZAG was found. Urine ZAG levels were positively correlated with UACR. Both ZAG levels were negatively correlated with eGFR. Urine ZAG levels in the eGFR ˃ 120 mL/min/1.73m2 subgroup were higher than that in the normal eGFR subgroup. CONCLUSION: These findings suggest that urine and serum ZAG might be useful as early biomarkers for detection of DN in T2DM patients, detectable earlier than microalbuminuria.

Cord blood concentrations of leptin, zinc-α2-glycoprotein, and adiponectin, and adiposity gain during the first 3 mo of life.

OBJECTIVES: Adipose tissue development starts in intrauterine life and cytokines are involved in this process. Therefore, understanding the role of cytokines in the fat mass gain of infants is crucial to prevent obesity later in life. Furthermore, recent evidence indicates a sex-specific link between cytokines and adipose tissue development. The objective of this study was to assess sex-specific relationships of cord blood concentrations of the cytokines leptin, zinc-α2-glycoprotein (ZAG), and adiponectin with infant adiposity during the first 3 mo of life. METHODS: This was a prospective cohort study of 104 mother-infant pairs that were selected from a maternity hospital in Sao Paulo, Brazil. Cord blood leptin, ZAG, and adiponectin were determined by enzyme-linked immunosorbent assays. The body composition of the infants was assessed monthly by air displacement plethysmography. A multiple linear regression analysis was conducted with the average fat mass gain from birth to the third month of life as the outcome and cord blood leptin, ZAG, and adiponectin as the variables of interest. RESULTS: Leptin was inversely associated with fat mass gain in the first 3 mo of life (P = 0.003; adjusted R2 = 0.09). There were inverse associations of leptin (P = 0.021), ZAG (P = 0.042), and maternal body mass index (P = 0.04) with fat mass gain in girls (adjusted R2 = 0.29) but fat mass gain in boys was positively associated with gestational age (P = 0.01; adjusted R2 = 0.15). CONCLUSIONS: The results of this study suggest that adiposity programming is sex-specific, which highlights the need to investigate the different metabolic mechanisms that are involved in adipogenesis.

Effect of curcumin on visfatin and zinc-α2-glycoprotein in a rat model of non-alcoholic fatty liver disease.

PURPOSE:: To investigate the effect of curcumin on visfatin and zinc-α2-glycoprotein (ZAG) expression levels in rats with non-alcoholic fatty liver disease (NAFLD). METHODS:: Fifty-six male rats were randomly divided into a control group (n=16) and model group (n=40) and were fed on a normal diet or a high-fat diet, respectively. Equal volumes of sodium carboxymethyl cellulose (CMC) were intragastrically administered to the control group for 4 weeks. At the end of the 12th week, visfatin and ZAG protein expression levels were examined by immunohistochemistry. Visfatin mRNA levels were measured by semi-quantitative reverse transcription polymerase chain reaction. RESULTS:: Compared with the control group, the model group showed significantly increased expression of visfatin in liver tissue (P < 0.01) and significantly decreased expression of ZAG (P < 0.01). These effects were ameliorated by curcumin treatment. CONCLUSIONS:: Visfatin and zinc-α2-glycoprotein may be involved in the pathogenesis of NAFLD. Treatment of NAFLD in rats by curcumin may be mediated by the decrease of visfatin and the increase of non-alcoholic fatty liver disease.

Zinc-α2-glycoprotein: is there association between this new adipokine and body composition in hemodialysis patients?

Peptides involved in the regulation of body composition are of interest in hemodialysis (HD) patients because protein wasting associated with high fat mass (FM) is present in these patients. Zinc-α2-glycoprotein (ZAG), a new adipokine, is involved in the regulation of lipid metabolism, adiposity, and energy balance. The purpose of this study was to evaluate ZAG levels and its relationship with body composition and dietary intake in HD patients. Forty-nine HD patients (28 men, 53.1 ± 12.5 years, and BMI 24.0 ± 4.3 kg/m2) were studied and compared with 20 healthy subjects (9 men, 49.5 ± 15.2 years, and BMI 25.6 ± 4.1 kg/m(2)). Plasma ZAG levels were measured using the ELISA methods and body composition was evaluated through anthropometric data. Dietary intake was assessed 3 days by 24-hour food recall. Although most of the HD patients (59.2%) were eutrophic according to BMI, 92.3% presented high percentage of body fat (BF), and 43.5%, reduced fat-free mass according to midarm muscle circumference values. ZAG levels were ∼2.5-fold higher in HD patients (135.9 ± 40.9 mg/L) compared with healthy individuals (54.6 ± 23.0 mg/L) (p < 0.0001). Circulating ZAG was not associated with dietary intake; however, this peptide was negatively correlated with %BF and, for each 1% reduction in BF, ZAG levels increased by 2.4 mg/L (p = 0.02). In summary, circulating ZAG is increased and inversely correlated with adiposity in HD patients; however, in spite of its higher plasma levels, the majority of HD patients did not show low BF.

Is zinc-α2-glycoprotein a cardiovascular protective factor for patients undergoing hemodialysis?

BACKGROUND: Zinc-α2-glycoprotein (ZAG) is a lipid mobilizing factor. Its anti-inflammatory action and expression pattern suggest that ZAG could act by protecting against the obesity-associated disorders. In hemodialysis (HD) patients, ZAG levels were described to be elevated but its effects on markers of inflammation and LDL oxidation are still unclear. We investigated the relationship between ZAG and markers of systemic inflammation and LDL atherogenic modification profile in HD patients. METHODS: Forty-three patients regularly on HD were studied and compared to 20 healthy subjects. Plasma ZAG, adiponectin, electronegative LDL [LDL(-)], an atherosclerotic negatively charged LDL subfraction, and anti-LDL(-) autoantibodies levels were measured by ELISA. Markers of inflammation and atherogenic cell recruitment (TNF-α, interleukin-6, VCAM-1, ICAM-1, MCP-1 and PAI-1) were also determined. RESULTS: Inflammatory markers and atherogenic cell recruitment were higher in HD patients when compared to healthy subjects. ZAG levels were also higher in HD patients (151.5 ± 50.1 mg/l vs 54.6 ± 23.0 mg/l; p<0.0001) and its levels were negatively correlated with TNF-α (r=-0.39; p=0.001) and VCAM-1 (r=-0.52; p<0.0001) and, positively correlated with anti-LDL(-) autoantibodies (r=0.38; p=0.016). On multivariate analyses, plasma ZAG levels were independently associated with VCAM-1 (p=0.01). CONCLUSION: ZAG is inversely associated with markers of pro-atherogenic factors linked to systemic inflammation and oxidative stress. Thus, this adipokine may constitute a novel marker of a favorable metabolic profile regarding cardiovascular risk factors in HD population.

Salivary and serum proteomics in head and neck carcinomas: before and after surgery and radiotherapy.

Several body fluids have been evaluated as new sources for cancer biomarker discovery. In this context, salivary and serum proteomics seem promising diagnostic and predictive tools for head and neck diseases. In the present study, we performed a proteomic analysis of saliva and serum from patients presenting head and neck squamous cell carcinoma (HNSCC) and compared the results before and after therapy. In saliva of cancer patients, we observed an altered protein profile, including over-expression of PLUNC and zinc-alpha-2-glycoprotein. Both proteins may contribute to control tumor growth and, therefore, represent targets for new analysis. We also detected serotransferrin and a modified transthyretin form with altered levels in serum from patients. Comparing preoperative and postreatment samples, the results showed that the protein profile after treatment reverted to a pattern closer to those observed for controls. These results add information on the role of secreted proteins in the cancer process and emphasize the potential of saliva and serum analysis for diagnosis and monitoring of HNSCC.