Serum Resistin, Adenylate Cyclase-Associated Protein 1 Gene Expression, and Carotid Intima-Media Thickness in Patients with End-Stage Renal Disease and Healthy Controls

Background: Human resistin is a proinflammatory cytokine with significant proatherogenic effects which acts through adenylyl cyclase-associated protein 1 (CAP1). Chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients have increased cardiovascular risk and resistin levels. Previous studies indicated resistin significance as a predictor of mortality in CKD. Aims: We sought to investigate plasma resistin levels, peripheral blood mononuclear cell (PBMC) resistin mRNA, and for the first time CAP1 mRNA levels in ESRD patients and healthy controls. We also sought to investigate the relation of resistin and CAP1 to carotid intima media thickness (CIMT), CD36 gene expression, and matrix metalloproteinase 9 (MMP-9) circulating levels in ESRD patients and healthy controls. Methods: This study included 33 patients with ESRD and 27 healthy controls. Resistin and MMP-9 levels were measured by ELISA. Resistin, CAP1, and CD36 PBMC mRNA were measured by quantitative PCR. Results: Our study showed that ESRD patients have significantly higher levels of circulatory resistin compared to healthy controls (p < 0.001), while there was no significant difference in resistin mRNA. A significant upregulation of CAP1 and CD36 was observed in the ESRD group (p < 0.001; p < 0.001). Resistin concentration correlated with CIMT in healthy controls (r = 0.512, p = 0.036), and with MMP-9 concentration in ESRD (r = 0.353, p = 0.044) and healthy controls (r = 0.463, p = 0.026). CAP1 correlated positively with CIMT (r = 0.464, p = 0.008) in ESRD, and with CD36 in healthy controls (r = 0.447, p = 0.022) and ESRD (r = 0.824, p < 0.001). Conclusion: The obtained data suggest that high levels of circulating resistin acting upon cells with an upregulated CAP1 gene could contribute to the increased inflammation and accelerated atherosclerosis seen in CKD patients.

Visfatin and resistin in gonadotroph cells: expression, regulation of LH secretion and signalling pathways

Visfatin and resistin appear to interfere with reproduction in the gonads, but their potential action at the hypothalamic–pituitary level is not yet known. The aim of the present study was to investigate the mRNA and protein expression of these adipokines in murine gonadotroph cells and to analyse the effects of different concentrations of recombinant mouse visfatin and resistin (0.01, 0.1, 1 and 10 ng mL−1) on LH secretion and signalling pathways in LβT2 cells and/or in primary female mouse pituitary cells. Both visfatin and resistin mRNA and protein were found in vivo in gonadotroph cells. In contrast with resistin, the primary tissue source of visfatin in the mouse was the skeletal muscle, and not adipose tissue. Visfatin and resistin both decreased LH secretion from LβT2 cells after 24 h exposure of cells (P < 0.03). These results were confirmed for resistin in primary cell culture (P < 0.05). Both visfatin (1 ng mL−1) and resistin (1 ng mL−1) increased AMP-activated protein kinase α phosphorylation in LβT2 cells after 5 or 10 min treatment, up to 60 min (P < 0.04). Extracellular signal-regulated kinase 1/2 phosphorylation was transiently increased only after 5 min resistin (1 ng mL−1) treatment (P < 0.01). In conclusion, visfatin and resistin are expressed in gonadotroph cells and they may affect mouse female fertility by regulating LH secretion at the level of the pituitary.

Hyperglycemia-induced changes in resistin gene expression in white adipose tissue in piglets

Previous data strongly indicated that resistin, an adipocyte-derived signalling peptide, plays an important role in metabolism and glucose homeostasis. Thus, the aim of the present study was to examine changes in synthesis and concentration of resistin in white adipose tissue in response to hyperglycemia in piglets. In order to develop hyperglycemia, piglets (10-week-old, Polish Landrace fatteners, female) received intraperitoneal (ip) injection of 150 mg streptozotocin (HI, n=6) or 60 mg synthetic glucocorticoid (HII, n=6). An injection of NaCl physiological saline was used as a control (n=6). Plasma resistin level was significantly higher in HII group compared with the control, while no difference was observed in HI. In epicardial adipose tissue (EAT ) the resistin mRNA level significantly increased whereas the opposite effect was observed for omental fat tissue (OAT ) in both experimental groups. Additionally, the resistin concentration did not change in EAT ; however, it was decreased in omental adipose tissue in response to hyperglycemia. The results obtained indicate that activity of resistin strongly depends on glycemic status as well as adipose tissue localization.

Lipopolysaccharide inhibits the expression of resistin in adipocytes

Resistin is an adipocytokine leading to insulin resistance. Endotoxin/lipopolysaccharide (LPS) has been reported to decrease the expression of resistin mRNA and protein in both lean and db/db obese mice, although the underlying mechanism remains unclear. Several models such as ex vivo culture of adipose tissues, primary rat adipocytes and 3T3-L1 adipocytes were used to further characterize the effect of LPS on the expression of resistin. LPS attenuated both the resistin mRNA and protein in a time- and dose-dependent manner. In the presence of actinomycin D, LPS failed to reduce the half-life of resistin mRNA, suggesting a transcriptional mechanism. The lipid A fraction is crucial for the inhibition of resistin expression induced by LPS. Pharmacological intervention of c-Jun N-terminal kinase (JNK) reversed the inhibitory effect of LPS. LPS down-regulated CCAAT/enhancer-binding protein α (C/EBP-α; CEBPA) and peroxisome proliferator-activated receptor γ (PPAR-γ; PPARG), while activation of C/EBP-α or PPAR-γ by either over-expressing these transcriptional factors or by rosiglitazone, an agonist of PPAR-γ, blocked the inhibitory effect of LPS on resistin. C/EBP homologous protein (CHOP-10; DDIT3) was up-regulated by LPS, while a CHOP-10 antisense oligonucleotide reversed the decrement of resistin protein induced by LPS. Taken together, these results suggest that LPS inhibits resistin expression through a unique signaling pathway involving toll-like receptor 4, JNK, CHOP-10 and C/EBP-α/PPAR-γ.

Paprika Pigments Attenuate Obesity-Induced Inflammation in 3T3-L1 Adipocytes

Obesity is related to various diseases, such as diabetes, hyperlipidemia, and hypertension. Adipocytokine, which is released from adipocyte cells, affects insulin resistance and blood lipid level disorders. Further, adipocytokine is related to chronic inflammation in obesity condition adipocyte cells. Paprika pigments (PPs) contain large amounts of capsanthin and capsorubin. These carotenoids affect the liver and improve lipid disorders of the blood. However, how these carotenoids affect adipocyte cells remains unknown. Present study examined the effects of PP on adipocytokine secretion, which is related to improvement of metabolic syndrome. In addition, suppressive effects of PP on chronic inflammation in adipocyte cells were analyzed using 3T3-L1 adipocyte cells and macrophage cell coculture experiments. PP promoted 3T3-L1 adipocyte cells differentiation upregulated adiponectin mRNA expression and secretion. Further, coculture of adipocyte and macrophage cells treated with PP showed suppressed interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), and resistin mRNA expression, similarly to treatment with troglitazone, which is a PPARγ ligand medicine. Conclusion. These results suggest that PP ameliorates chronic inflammation in adipocytes caused by obesity. PP adjusts adipocytokine secretion and might, therefore, affect antimetabolic syndrome diseases.

Resistin Gene Expression in Visceral Adipose Tissue of Postmenopausal Women and its Association with Insulin Resistance

Aim: The present study evaluates resistin mRNA expression in visceral adipose tissue (VAT) and its correlation with insulin resistance (homeostatic model assessment) in postmenopausal obese women. Materials & methods: A total of 68 (nonobese = 34 and obese = 34) age-matched (49–70 years) postmenopausal women were recruited for the study. Fasting blood samples were collected at admission and abdominal VAT were obtained during surgery for gall bladder stones or hysterectomy. Physical parameters (age, height, weight and BMI) were measured. Biochemical parameters (plasma insulin, plasma glucose and serum resistin) were estimated by enzymatic methods. The VAT resistin mRNA expression was evaluated by real-time PCR. Results: The relative mean (± standard deviation) VAT resistin mRNA expression in postmenopausal obese women lowered significantly by 20.4% compared with postmenopausal nonobese women (0.029 ± 0.011 vs 0.023 ± 0.013; p = 0.047). Furthermore, VAT resistin mRNA expression in postmenopausal obese women was downregulated by 0.69-fold when compared with age-matched postmenopausal nonobese women. Furthermore, the relative VAT resistin mRNA expression in postmenopausal obese women showed significant inverse association with insulin resistance (r = −0.48; p < 0.01) and serum resistin (r = −0.84; p < 0.001), while in postmenopausal nonobese women it did not show any association with both insulin resistance (r = 0.03; p > 0.05) and serum resistin (r = −0.03; p > 0.05). Conclusion: The VAT resistin mRNA expression in postmenopausal obese women is associated to insulin resistance.