Vaspin facilitates the proliferation and osteogenic differentiation of periodontal ligament stem cells.

OBJECTIVE: To investigate whether visceral adipose tissue-derived serine protease inhibitor (vaspin) can alleviate the inhibitory effect of high-glucose (HG) culture on the proliferation and osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) and to preliminarily explore the underlying mechanisms. BACKGROUND: High glucose produces damage to the regeneration of periodontal tissue of PDLSCs. The expression level of vaspin in periodontal tissue is high in periodontitis patients and effectively reduced after initial therapy of periodontal diseases. However, the effect of vaspin on PDLSCs remains unknown. MATERIALS AND METHODS: PDLSCs were cultured in media augmented with 5.5 or 25.0 mM concentrations of glucose to elucidate the impact and mechanism of vaspin on PDLSCs under high glucose in vitro. Proliferation was measured by Cell Counting Kit-8 (CCK8) assay. Osteogenesis of PDLSCs was assessed by alkaline phosphatase (ALP) staining, ALP activity, and Alizarin Red staining. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) were used to investigate the osteo-specific markers. Then, the molecular impact of vaspin in the presence/absence of HG on PDLSCs physiology was determined with TGF-ß1/Smad signaling pathway as the main focus. RESULTS: It was revealed that the proliferation and osteogenic differentiation (OD) of PDLSCs under HG was reduced, and by adding vaspin the anti-osteogenic impact of HG was relieved. Moreover, vaspin enhanced TGF-ß1/Smad signaling pathway activity. Pretreatment with TGF-ß1 inhibitor blocked vaspin-triggered TGF-ß1/Smad signal activation and minimized the vaspin-induced protective effect against HG-inhibited growth and OD. CONCLUSIONS: In summary, vaspin observably reduces HG-mediated inhibition of PDLSCs OD by modulating the TGF-ß1/Smad signaling pathway. Vaspin may be a potential therapeutic for periodontal tissue regeneration in diabetic patients.

The in vitro mechanism of Vaspinregulates the proliferation and steroidogenesis of rat lutein cells.

OBJECTIVE: Stable luteal cell function is an important prerequisite for reproductive ability and embryonic development. However, luteal insufficiency seriously harms couples who have the desire to have a pregnancy, and the most important thing is that there is no complete solution. In addition, Vaspin has been shown to have regulatory effects on luteal cells, but the complex mechanisms involved have not been fully elucidated. Therefore, this study aimed to explore the effect of Vaspin on rat luteal cells and its mechanism. METHODS: Granulosa lutein cells separated from the ovary of female rats were incubated for 24h with gradient concentrations of Vaspin, and granulosa lutein cells incubated with 0.5% bovine serum albumin were used as controls. The proliferation, apoptosis, angiogenesis, progesterone (P4) and estradiol (E2) were detected by CCK-8, Anneixn-FITC/PI staining, angiogenesis experiment and ELISA. Western blot was applied to observe the expression levels of proteins related to cell proliferation, apoptosis, angiogenesis and MEK/MAPK signaling pathway. RESULTS: Compared with the Control group, Vaspin could significantly up-regulate the proliferation of granulosa lutein cells and reduce the apoptosis. Moreover, Vaspin promoted the angiogenesis of granulosa lutein cells and the production of P4 and E2 in a concentration-dependent manner. Furthermore, Vaspin up-regulated the CyclinD1, CyclinB1, Bcl2, VEGFA and FGF-2 expression in granulosa lutein cells, and down-regulated the level of Bax. Also, Vaspin increased the p-MEK1 and p-p38 levels. CONCLUSION: Vaspin can up-regulate the proliferation and steroidogenesis of rat luteal cells and reduce apoptosis, which may be related to the influence of MEK/MAPK activity.

Progranulin and Vaspin as Potential Novel Markers in the Etiology of Type 1 Diabetes in Children.

Background and Objectives: Diabetes is a significant health problem, prompting the search for new therapeutic strategies. Recently, researchers have focused on identifying novel markers for the progression of this condition. It is well established that adipokines, such as progranulin and vaspin, play crucial roles in regulating lipid and carbohydrate metabolism. Materials and Methods: This single-center cross-sectional study aimed to assess serum progranulin and vaspin levels in 80 children diagnosed with type 1 diabetes (T1D) and to examine their correlation with body mass index (BMI), glycated hemoglobin, and lipid profile. The cohort included 40 children newly diagnosed with diabetes, 40 children with long-term diabetes (20 well-controlled and 20 poorly controlled), and 14 non-diabetic children as a control group. Progranulin and vaspin levels were determined using a sandwich enzyme-linked immunosorbent assay. Results: There were no significant differences in the progranulin and vaspin concentrations in the studied groups (p = 0.246 and p = 0.095, respectively). No statistically significant differences were noted in the levels of both adipokines among boys and girls within the T1D, well-controlled T1D, and poorly controlled T1D groups. We did not find any differences in the progranulin and vaspin levels among all children with T1D and healthy controls when divided based on BMI percentiles. A negative correlation was observed between progranulin concentration and the age of children in the T1D, well-controlled T1D, and healthy groups. Furthermore, progranulin correlated negatively with BMI among children with T1D. In contrast, vaspin concentration correlated positively with age among healthy children. Conclusions: Our study provides novel insights into the status of progranulin and vaspin among pediatric participants with varying levels of type 1 diabetes control. However, further research involving larger patient cohorts and different stages of sexual maturation is warranted.

Vaspin alleviates the lncRNA LEF1-AS1-induced osteogenic differentiation of vascular smooth muscle cells via the Hippo/YAP signaling pathway.

Vascular calcification (VC) is closely related to higher cardiovascular mortality and morbidity, and vascular smooth muscle cell (VSMC) switching to osteogenic-like cells is crucial for VC. LncRNA LEF1-AS1 promotes atherosclerosis and dental pulp stem cells calcification, while its role in VC remains unknown. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipokine regulating bone metabolism. However, the relationship between vaspin and VC is still unclear. We aimed to explore the role of LEF1-AS1 on VSMC osteogenic transition, whether vaspin inhibited LEF1-AS1-mediated osteogenic differentiation of VSMCs, and the responsible mechanism. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis indicated that LEF1-AS1 overexpression significantly upregulated osteogenic marker Runt-related transcription factor-2 (RUNX2) level and downregulated VSMC contractile marker α-smooth muscle actin (α-SMA) level. Alizarin red staining, alkaline phosphatase (ALP) staining, ALP activity assay, and calcium content assay also suggested that LEF1-AS1 overexpression promoted calcium deposition in VSMCs. However, vaspin treatment abolished this phenomenon. Mechanistically, LEF1-AS1 markedly decreased phosphorylated YAP level, while vaspin reversed LEF1-AS1-induced phosphorylated YAP decline. Our results revealed that LEF1-AS1 accelerated the osteogenic differentiation of VSMCs by regulating the Hippo/YAP pathway, while vaspin eliminated the LEF1-AS1-meditated VSMCs osteogenic phenotype switch.

Serum vaspin as a predictor of severity and prognosis in acute ischemic stroke patients.

Objective: The influence of vaspin on vascular health had been investigated, yielding conflicting results. This study is intended to investigate the relation between vaspin and stroke severity and stroke outcome in a cohort Chinese patient with acute ischemic stroke (AIS).Methods: This was a prospective single-center observational study in Xinxiang, China. From 1 July 2017 to 30 November 2019, all patients with first-ever AIS were consecutively included. Serum levels of vaspin, stroke severity at (assessed by NIHSS score) admission and functional outcome (assessed by modified Rankin Scale (mRS)) at discharge were recorded. Multivariate analyses were assessed using logistic regression models.Results: Finally, 340 patients with AIS were included. The median age of those patients was 65 (interquartile range [IQR], 56-74) years and 61.8% were men. At admission, 88 patients (25.9%) experienced severe stroke (NIHSS>10) and serum levels of vaspin (median [IQR]: 0.72[0.48-0.90]ng/ml) in those patients were significantly lower than in those mild(0.92[0.70-1.19]ng/ml) and moderate stroke (0.93[0.63-1.21]ng/ml). At discharge, 113 patients (33.2%) experienced poor functional outcome (mRS >2) and vaspin serum levels in those patients were lower as compared with patients who experienced good outcome (0.71[0.45-0.98] vs. 0.91[0.71-1.19]ng/ml). In multivariate analyses, lower level of vaspin (< median) was associated with a 2.5-fold (odds ratio [OR] 2.46; 95% confidence interval [CI]: 1.75-4.45) increased risk for severe stroke and a 2.1-fold (2.03; 1.42-3.58) increased risk for poor outcome.Conclusion: In conclusion, reduced serum levels of vaspin at admission are significantly related to stroke severity and prognosis, which illustrates a predictive role of reduced vaspin in ischemic stroke.

Association of circulating vaspin levels and patients with metabolic-associated fatty liver disease: a systematic review and meta-analysis.

BACKGROUND: The incidence rate of metabolic-associated fatty liver disease (MAFLD) is increasing annually; however, there are still no effective methods for establishing an early diagnosis and conducting real-time tracing. Vaspin can affect the metabolic processes in the body, and it is closely associated with many metabolic diseases. Many previous studies have speculated on the association between vaspin and MAFLD, but the results of these studies have not been conclusive. This meta-analysis examined the differences in circulating vaspin levels between patients with MAFLD and healthy individuals. METHODS: Six databases and other sources were searched with free terms and Medical Subject Headings terms, and a total of 13 articles were included (900 cases and 669 controls). RevMan 5.3 and Stata 16 were used for analysis. The standardised mean difference (SMD) and 95% confidence interval (CI) were used to assess the overall outcomes. Cohen's kappa coefficient was applied to examine the differences between the two authors in the selection of studies and in the evaluation of the quality of evidence for the studies. RESULTS: The results demonstrated that there was no significant difference in the circulating vaspin levels between the MAFLD group and healthy group (SMD = 0.46, 95% CI: [- 0.12, 1.04]). The subgroup analysis suggested that area and body mass index (BMI) may be the sources of heterogeneity, and the results of univariate meta-regression analysis were consistent with those of the subgroup analysis (P = 0.005 and P < 0.001, respectively). Furthermore, BMI may better explain the source of heterogeneity (P = 0.032) in the multivariate meta-regression analysis. CONCLUSION: In summary, no significant correlation was observed between the circulating vaspin levels and MAFLD. BMI may be an important factor affecting this correlation, which may provide a reference for further studies on mechanism and diagnosis of MAFLD.

Vaspin promotes chondrogenic differentiation of BMSCs via Akt activation in osteoarthritis.

BACKGROUND: The aim of this study was to investigate the role of Vaspin on the chondrogenic differentiation of bone mesenchymal stem cells (BMSCs), and its effect on chondrocyte survival and ECM secretion. We also assessed whether the Akt activation participates in these processes. METHODS: In vivo, immunohistochemistry was used to examine the positive rate of the protein expressions of Akt in Wistar rat articular cartilage and subchondral bone after Vaspin intraperitoneal injection for 14 days. In vitro, we isolated and expanded BMSCs from Wistar rats, and further cultured BMSCs as pellets in a chondrogenic-differentiation medium supplemented with different concentrations of Vaspin. After 21 days, the pellets were processed for cell counting kit assay. The mRNA level of Akt, SOX9 and COL2A1 in the pellets were investigated using quantitative Real-Time polymerase chain reaction, and the protein level of COMP was detected using western blot. RESULTS: During the chondrogenic differentiation of BMSCs, Vaspin promoted the chondrogenic differentiation of BMSCs and chondrocyte survival by activating the Akt pathway. These effects were significantly reduced by treatment with an Akt inhibitor. Moreover, Vaspin promoted chondrogenic differentiation of BMSCs by increasing the expression of markers in cartilage formation and extracellular matrix secretion. Furthermore, our study also found that Vaspin could increase Akt expression in cartilage cavities and subchondral bone in vivo. CONCLUSION: These findings demonstrate that Vaspin can promote the chondrogenic differentiation of BMSCs and chondrocyte survival via Akt activation. Our study provides new insights into the potential ability of Vaspin to ameliorate the chondrogenic differentiation of BMSCs and chondrocyte survival in OA.

Decreased levels of vaspin and its potential association with cardiometabolic risk in patients with psoriasis: preliminary results.

Introduction: Omentin and vaspin are considered to have beneficial effects preventing the development of metabolic disorders which are common comorbidities in psoriasis. Aim: To evaluate the serum level of these adipokines in psoriatic patients and elucidate possible associations with disease activity, metabolic or inflammatory parameters and systemic treatment. Material and methods: Thirty-three patients with active plaque-type psoriasis and 11 healthy controls participated in the study. Blood samples were collected before and after 3 months of treatment with acitretin or methotrexate. Results: Serum vaspin concentration in psoriatic patients was significantly lower than in the control group (p < 0.05). No correlation between adipokines and severity of disease evaluated with PASI was found. However, median vaspin levels decreased with the severity of skin lesions and the omentin level was higher in patients with severe disease versus those with moderate form (p < 0.05). The vaspin level correlated with BMI of psoriatic patients (p < 0.05), with cholesterol and triglycerides levels (p = 0.054, p = 0.049, respectively). No significant effect of systemic treatment on omentin levels was found. Regarding vaspin, we observed an upward trend in its concentration after treatment. Conclusions: Omentin and vaspin may play a modulating role in the systemic inflammation present in psoriasis and thus may contribute to the development of metabolic complications.

Association of vaspin rs2236242 gene variants and circulating serum vaspin concentrations with coronary artery disease in a Turkish population.

Coronary artery disease (CAD) is the primary cause of death worldwide. Vaspin was a recently described adipokine, playing a protective role in many metabolic and cardiovascular diseases. This study aimed to assess the relation of serum vaspin levels and vaspin rs2236242 polymorphisms with CAD. The study included 105 healthy subjects and 105 CAD patients. Serum vaspin concentrations and vaspin rs2236242 polymorphisms were determined by enzyme-linked immunosorbent assay and polymerase chain reaction, respectively. There was a statistically significant difference between the genotypes of CAD patients (TT 26.7%, TA 71.4%, and AA 1.9%) and controls (TT 70.5%, TA 28.6%, and AA 1%; χ2 = 40.3; df = 2; p = .000). The TA genotype increased the risk of CAD (odds ratio [OR] = 6.60; 95% confidence interval [CI] = 3.60-12.1; p = .000) as compared to the TT genotype. There was a statistically significant difference between the allelic distribution of CAD patients (T 62.4% and A 37.6%) and controls (T 84.8% and A 15.2%; χ2 = 27.0; df = 1; p = .000). Those carrying the A allele had a higher risk of CAD compared to those with the T allele (OR = 3.35; 95% CI = 2.10-5.36; p = .000). The serum vaspin concentrations of the patients with TT, TA, and AA genotypes were 30.4 ± 1.72, 28.4 ± 2.89, and 36.4 ± 6.38 pg/ml, respectively, and there was no significant difference between the serum vaspin levels and vaspin genotypes (p = .696). All of the above suggested that the vaspin rs2236242 polymorphism was associated with CAD in the Turkish population.

Omentin-1 and vaspin serum levels in patients with pre-clinical carotid atherosclerosis and the effect of statin therapy on them.

BACKGROUND: Omentin-1 and vaspin are novel adipokines, and their association with atherosclerosis is still under investigation. The present study aimed to assess the relationship of those adipokines with preclinical, non-significant carotid atherosclerosis and the impact of statin therapy on their levels, suggesting a link between adiposity and atherosclerosis. METHODS: Eighty-four statin-free subjects with non-significant, preclinical carotid atherosclerosis and elevated LDL- cholesterol levels (>130 mg/dl) were recruited to receive atorvastatin (from 10 to 80 mg per day) (atorvastatin group - AG group). Forty-six age- and gender-matched healthy individuals, without any chronic disease served as controls (control group - CG). Clinical parameters, metabolic profile, serum omentin-1, vaspin concentrations and ultrasound measurements of carotid thickening were obtained at the beginning and after 12 months. RESULTS: At baseline, AG showed lower omentin-1 and vaspin serum levels than CG (p ≤ 0.001). Along the entire study population at baseline, omentin-1 levels were independently related to LDL-cholesterol, while vaspin levels were independently associated with hsCRP and the presence of carotid atherosclerosis (p < 0.05). Within AG, 12-months atorvastatin treatment significantly increased omentin-1 (from 202.79 ± 91.41 ng/ml to 262.56 ± 101 ng/ml, p < 0.001) and vaspin concentrations (from 1.29 ± 0.51 ng/ml to 1.70 ± 0.5 ng/ml, p = 0.002). In standard multiple regression analysis, the presence of carotid atherosclerosis related to baseline vaspin levels (ß = -0.232, p < 0.001), while the atorvastatin-induced increase of vaspin was independently associated with hsCRP reduction (ß = -0.198, p = 0.045). CONCLUSION: Low omentin-1 and vaspin serum levels associated with preclinical, non-significant carotid atherosclerosis. Notably, atorvastatin administration significantly increased both adipokines, but the underlying mechanisms and the clinical impact of those changes requires further investigation.

Serum vaspin levels and carotid intima-media thickness in predialysis patients.

BACKGROUND AND OBJECTIVE: Visceral adipose tissue-derived serine proteinase inhibitor (vaspin) is an adipokine that correlates with insulin resistance and obesity in human beings. Previous studies have evaluated the serum vaspin levels in several diseases such as chronic haemodialysis patients and coronary artery disease. To our knowledge, serum vaspin levels have not yet been reported in predialysis patients. Carotid intima-media thickness (CIMT) is a noninvasive procedure to detect early atherosclerotic changes. The aim of this study was to evaluate serum vaspin levels in predialysis patients and their relationships with glomerular filtration rate and CIMT levels. METHODS: A total of twenty-five predialysis patients (14 females and 11 males) and 22 healthy subjects (8 females and 14 males) were enrolled in the study. Serum samples were subjected to the human vaspin RIA system. CIMT was measured by B-mode ultrasonography. RESULTS: Serum vaspin levels were significantly lower in predialysis patients than control subjects (P < .05), while CIMT levels were significantly higher (P < .001). Serum vaspin levels were found to be significantly correlated with glomerular filtration rate (r = 0.42, P < .001) and CIMT (r = -0.47, P < .05) in predialysis patients. CONCLUSIONS: This is the first report to describe the association between serum vaspin levels and CIMT in predialysis patients. We concluded that serum vaspin levels were decreased in predialysis patients than control subjects. In addition, serum vaspin levels were found to be significantly correlated with glomerular filtration rate and CIMT.

The Role of Anti-Inflammatory Adipokines in Cardiometabolic Disorders: Moving beyond Adiponectin.

The global burden of obesity has multiplied owing to its rapidly growing prevalence and obesity-related morbidity and mortality. In addition to the classic role of depositing extra energy, adipose tissue actively interferes with the metabolic balance by means of secreting bioactive compounds called adipokines. While most adipokines give rise to inflammatory conditions, the others with anti-inflammatory properties have been the novel focus of attention for the amelioration of cardiometabolic complications. This review compiles the current evidence on the roles of anti-inflammatory adipokines, namely, adiponectin, vaspin, the C1q/TNF-related protein (CTRP) family, secreted frizzled-related protein 5 (SFRP5), and omentin-1 on cardiometabolic health. Further investigations on the mechanism of action and prospective human trials may pave the way to their clinical application as innovative biomarkers and therapeutic targets for cardiovascular and metabolic disorders.

Antepartum and postpartum changes in adipokines, endothelial dysfunction, inflammatory markers and other biochemical parameters in preeclamptic women: A prospective observational cohort study.

This study aimed at evaluating the role played by insulin resistance, lipid metabolism disorder, oxidative stress, resistin, vaspin, Interleukin-18 and asymmetric dimethyl arginine as a marker for endothelial dysfunction in the pathogenesis of preeclampsia. This prospective observational cohort study involved 60 women who were classified into: 20 non-pregnant women (group 1 or control group), 20 normally pregnant women (group 2) and 20 preeclamptic women (group 3) at their third trimester. The pregnant women were assessed at their third trimester and further re-evaluated four weeks after delivery. The assessment included demography, assessment of proteinuria and urinary protein to creatinine ratio, blood pressure measurement and assessment of fasting blood glucose, fasting insulin level, lipid panel and the circulating levels of malondialdehyde, resistin, vaspin, interleukin-18 and asymmetric dimethyl arginine. Preeclamptic women showed more atherogenic lipid profile, significantly higher Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and significantly elevated levels of malondialdehyde, resistin, vaspin and interleukin-18 than the other study groups. Serum asymmetric dimethyl arginine concentration showed non-significant difference among the three study groups. The levels of resistin and vaspin showed significant decrease four weeks postpartum in preeclamptic group. We concluded that, preeclampsia was associated with insulin resistance, dyslipidemia, oxidative stress, inflammation and significant changes in adipokines; resistin and vaspin. Furthermore, the significant increase in the serum levels of resistin and vaspin at the third trimester and their significant decline four weeks postpartum in preeclamptic group focus the attention on the role played by these adipokines in the pathogenesis of preeclampsia.

Correlation of Serum Vaspin, Omentin-1, and adiponectin with metabolic phenotypes in Type-2 diabetes mellitus patients.

OBJECTIVES: To investigate adipocytokines' (vaspin, omentin-1, and adiponectin) correlation with metabolic phenotypes in type 2 diabetes mellitus (T2DM) patients. METHODS: This case-control research was done at the Diabetic Clinic in Jeddah, Kingdom of Saudi Arabia (KSA), from November 2018 to March 2019. Seventy-five T2DM patients and 75 gender, age, and BMI-matched healthy subjects were recruited for this research. RESULTS: In DM patients, the concentrations of serum vaspin and omentin-1 were substantially lower (p<0.001) than in the control group. A significant positive relationship between vaspin concentration and DBP (p<0.001), BMI (p<0.001), and waist circumference (p<0.001) was found in patients and control subjects, while FPG (p<0.016), serum insulin (p<0.001), HOMA-IR (p<0.001), TC (p<0.001), TG (p<0.001), and LDLc (p<0.001) were significantly interrelated among patients. Serum concentrations of omentin-1 and ADN were significantly negatively correlated with serum insulin, HOMA-IR, and TG among the DM group. Serum vaspin and ADN levels were significantly higher in the cases and control groups with BMI>25, and no gender-wise variance was observed in adipocytokines levels. Binary logistic regression analysis showed a significantly negative predictive relationship of vaspin and omentin-1 with DM. CONCLUSION: The DM group displayed substantially lower serum vaspin and omentin-1 levels. However, there was no consistent relationship observed between these adipocytokines and metabolic phenotypes.

Hepatic stellate cell activation promotes alcohol-induced steatohepatitis through Igfbp3 and SerpinA12.

BACKGROUND & AIMS: Steatohepatitis drives fibrogenesis in alcohol-related liver disease. Recent studies have suggested that hepatic stellate cells (HSCs) may regulate the parenchymal cell injury and inflammation that precedes liver fibrosis, although the mechanism remains incompletely defined. Neuropilin-1 (NRP-1) and synectin are membrane proteins implicated in HSC activation. In this study, we disrupted NRP-1 and synectin as models to evaluate the role of HSC activation on the development of steatohepatitis in response to alcohol feeding in mice. METHODS: Mice with HSC-selective deletion of NRP (ColCre/Nrp1loxP) or synectin (ColCre/synectinloxP) vs. paired Nrp1loxP or synectinloxP mice were fed a control diet or the chronic/binge alcohol feeding model. Several markers of steatosis and inflammation were evaluated. RESULTS: ColCre/Nrp1loxP mice showed less fibrosis, as expected, but also less inflammation and steatosis, with lower hepatic triglyceride content. Similar results were observed in the synectin model. Hepatocytes treated with supernatant of HSCs from ColCre/Nrp1loxP mice compared to supernatant from Nrp1loxP mice were protected against ethanol-induced lipid droplet formation. An adipokine and inflammatory protein array from the supernatant of HSCs with NRP-1 knockdown showed a significant reduction in Igfbp3 (a major insulin-like growth factor-binding protein with multiple metabolic functions) and an increase in SerpinA12 (a serine-protease inhibitor) secretion compared to wild-type HSCs. Recombinant Igfbp3 induced lipid droplets, triglyceride accumulation, and lipogenic genes in hepatocytes in vitro, while SerpinA12 was protective against ethanol-induced steatosis. Finally, Igfbp3 was increased, and SerpinA12 was decreased in serum and liver tissue from patients with alcoholic hepatitis. CONCLUSION: Selective deletion of NRP-1 from HSCs attenuates alcohol-induced steatohepatitis through regulation of Igfbp3 and SerpinA12 signaling. LAY SUMMARY: Hepatic stellate cells are known for their role in fibrosis (scarring of the liver). In this study, we describe their role in the modulation of fat deposition and inflammation in the liver, which occurs secondary to alcohol damage.

Role of vaspin in porcine ovary: effect on signaling pathways and steroid synthesis via GRP78 receptor and protein kinase A†.

Vaspin, visceral-adipose-tissue-derived serine protease inhibitor, is involved in the development of obesity, insulin resistance, inflammation, and energy metabolism. Our previous study showed vaspin expression and its regulation in the ovary; however, the role of this adipokine in ovarian cells has never been studied. Here, we studied the in vitro effect of vaspin on various kinase-signaling pathways: mitogen-activated kinase (MAP3/1), serine/threonine kinase (AKT), signal transducer and activator of transcription 3 (STAT3) protein kinase AMP (PRKAA1), protein kinase A (PKA), and on expression of nuclear factor kappa B (NFKB2) as well as on steroid synthesis by porcine ovarian cells. By using western blot, we found that vaspin (1 ng/ml), in a time-dependent manner, increased phosphorylation of MAP3/1, AKT, STAT3, PRKAA1, and PKA, while it decreased the expression of NFKB2. We observed that vaspin, in a dose-dependent manner, increased the basal steroid hormone secretion (progesterone and estradiol), mRNA and protein expression of steroid enzymes using real-time PCR and western blot, respectively, and the mRNA of gonadotropins (FSHR, LHCGR) and steroids (PGR, ESR2) receptors. The stimulatory effect of vaspin on basal steroidogenesis was reversed when ovarian cells were cultured in the presence of a PKA pharmacological inhibitor (KT5720) and when GRP78 receptor was knocked down (siRNA). However, in the presence of insulin-like growth factor type 1 and gonadotropins, vaspin reduced steroidogenesis. Thus, vaspin, by activation of various signaling pathways and stimulation of basal steroid production via GRP78 receptor and PKA, could be a new regulator of porcine ovarian function.

Insight into adipokines to optimize therapeutic effects of stem cell for tissue regeneration.

Stem cell therapy is considered as a promising regenerative medicine for repairing and treating damaged tissues and/or preventing various diseases. But there are still some obstacles such as low cell migration, poor stem cell engraftment and decreased cell survival that need to be overcome before transplantation. Therefore, a large body of studies has focused on improving the efficiency of stem cell therapy. For instance, preconditioning of stem cells has emerged as an effective strategy to reinforce therapeutic efficacy. Adipokines are signaling molecules, secreted by adipose tissue, which regulate a variety of biological processes in adipose tissue and other organs including the brain, liver, and muscle. In this review article, we shed light on the biological effects of some adipokines including apelin, oncostatin M, omentin-1 and vaspin on stem cell therapy and the most recent preclinical advances in our understanding of how these functions ameliorate stem cell therapy outcome.

Association of vaspin gene expression and its serum level on the risk of ischemic stroke in type 2 diabetic Egyptian patients: Prospective case-control study.

We aimed to evaluate serum vaspin and its gene expression in patients with type 2 diabetes mellitus (T2DM) and to assess the association of serum vaspin and its gene expression with susceptibility of ischemic stroke (IS). The prospective case-control study included 50 healthy individuals in a control group, and 90 patients with and T2DM were stratified into two subgroups: patients with IS and patients without IS. The serum vaspin concentration was measured by enzyme-linked immunosorbent assay (ELISA). Real-time PCR was performed to detect the mRNA expression of vaspin. Serum vaspin and vaspin expression levels were significantly higher in IS compared to the non-IS group. Interestingly, they were positively correlated with other vascular and metabolic risks. Diastolic and systolic blood pressure, as well as hemoglobin A1c cholesterol (HbA1c), were independently correlated with serum vaspin. After adjusting for the traditional risk factors, the logistic regression analysis test was done to evaluate the predictor of IS among T2DM patients; the vaspin expression level was a statistical significance predictor of IS among T2DM patients. In conclusion, the higher levels of serum vaspin and vaspin expression levels in T2DM emphasizes the pivotal role of vaspin serum level and expression in the progression of metabolic and glucose abnormalities, thus, they could be used as biomarkers of IS.

Insulin induces expression of the hepatic vaspin gene.

Visceral adipose tissue-derived serine protease inhibitor (vaspin), initially identified in the visceral adipose tissue, is an adipokine that improves endoplasmic reticulum stress in obesity or insulin sensitivity and glucose tolerance. However, the transcriptional regulation of the hepatic vaspin gene remains elusive. We have previously shown that CCAAT-enhancer-binding protein α, a transcription factor of the basic leucine zipper class, positively regulates the vaspin gene. The present study aimed to investigate the nutritional or hormonal regulators of vaspin expression in the liver. For the fasting and refeeding study, mice in the fasting group were subjected to fasting for 24 h and then sacrificed. Mice in the refeeding group were subjected to fasting for 24 h and then refed with a 50% (w/w) sucrose/MF diet for further 24 h and then sacrificed. For the streptozotocin (STZ) study, STZ (50 mg/kg) was intraperitoneally injected into C57BL/6JJc1 mice for 5 d. Hepatic vaspin was repressed due to fasting for 24 h and was induced upon refeeding with a high-sucrose diet. In studies on liver-specific C/EBPα-deficient mice, C/EBPα was not involved in the induction of hepatic vaspin upon refeeding. In addition, the depletion of insulin by streptozotocin treatment markedly decreased hepatic vaspin expression. Finally, fasting-repressed vaspin expression in the liver was significantly increased by direct injection of insulin into fasting mice. In conclusion, our results suggest that insulin is a positive regulator of hepatic vaspin expression.

Association between Vaspin rs2236242 Gene Polymorphism and Psoriasis Vulgaris.

BACKGROUND: Psoriasis known as a chronic inflammatory skin disease is accompanied by metabolic disorders such as obesity, diabetes, and dyslipidemia. Vaspin (a serine protease inhibitor derived from visceral adipose tissue) is a newly identified adipokine and a link between inflammation and obesity has been reported. We aimed to determine whether vaspin gene polymorphism is associated with the development and/or clinical features of psoriasis vulgaris. METHODS: Our study group consisted of 96 psoriasis vulgaris patients and 100 matched controls. Vaspin rs2236242 gene was genotyped using PCR. RESULTS: The vaspin genotypes showed a meaningful difference between psoriasis and control groups (p = 0.02). The frequency of the vaspin rs2236242 TT genotype was lower in psoriasis patients than in control participants (p < 0.05). The TA genotype was associated with a 2.38-fold increased risk of psoriasis compared to the TT genotype (p = 0.007, odds ratio: 2.38; 95% confidence interval: 1.25-4.55), but not the AA genotype. All subjects were the Turkish population, the study in other populations is needed and the sample size was small in number. CONCLUSION: Our study demonstrated that vaspin rs2236242 polymorphism is related to psoriasis in the Turkish population. Polymorphisms of the vaspin gene might serve as diagnostic biomarkers of psoriasis.