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Accumulating discoveries highlight the importance of interaction between marrow stromal cells and cancer cells for bone metastasis. Bone is the most common metastatic site of breast cancer and bone marrow adipocytes (BMAs) are the most abundant component of the bone marrow microenvironment. BMAs are unique in their origin and location, and recently they are found to serve as an endocrine organ that secretes adipokines, cytokines, chemokines, and growth factors. It is reasonable to speculate that BMAs contribute to the modification of bone metastatic microenvironment and affecting metastatic breast cancer cells in the bone marrow. Indeed, BMAs may participate in bone metastasis of breast cancer through regulation of recruitment, invasion, survival, colonization, proliferation, angiogenesis, and immune modulation by their production of various adipocytokines. In this review, we provide an overview of research progress, focusing on adipocytokines secreted by BMAs and their potential roles for bone metastasis of breast cancer, and investigating the mechanisms mediating the interaction between BMAs and metastatic breast cancer cells. Based on current findings, BMAs may function as a pivotal modulator of bone metastasis of breast cancer, therefore targeting BMAs combined with conventional treatment programs might present a promising therapeutic option. [ABSTRACT FROM AUTHOR]

Background: Obesity and metabolic syndrome are considered the risk factors of colorectal adenoma (CRA) and colorectal cancer (CRC). Chemerin is a novel adipocytokine associated with the development of gastric cancer, esophageal cancer, hepatocellular carcinoma, and CRC. However, the relationship between chemerin levels and CRA remains unclear. Objective: This study is aimed at investigating the -association between serum chemerin levels and the development of CRA. Methods: We conducted a total colonoscopy-based cross-sectional case-control study of 80 male patients with CRA and 80 male age-matched control individuals without CRA, according to their endoscopic findings. Serum chemerin concentrations were measured using a sandwich enzyme-linked immunosorbent assay kit, and the OR of CRA was calculated via logistic regression analysis. Results: The mean serum chemerin level of the CRA group was significantly higher than that of the control group (7.9 ± 0.41 vs. 5.16 ± 0.34 ng/mL, p < 0.001). Serum chemerin level was positively correlated to the development of CRA (r = 0.34). Multivariate logistic regression analysis revealed that a high chemerin level was independently associated with the development of CRA (OR 2.82, 95% CI 1.39–5.72). Conclusions: Our findings indicated that increased serum chemerin levels are positively associated with the presence of CRA in men. Chemerin may play an important role in the development of CRA. [ABSTRACT FROM AUTHOR]

Chemerin is an adipocytokine involved in inflammation and lipid metabolism via G protein-coupled receptor, chemokine-like receptor (CMKLR)1. Since the important nuclei regulating pressure (BP) exist in the brain, we examined the effects of acute intracerebroventricular (i.c.v.) injection of chemerin-9 on systemic BP and explored underlying mechanisms. We examined the effects of acute i.c.v. injection of chemerin-9 (10 nmol/head) on systemic BP by a carotid cannulation method in the control or CMKLR1 small interfering (si) RNA-treated Wistar rats (0.04 nmol, 3 days, i.c.v.). We examined protein expression of CMKLR1 around brain ventricles by Western blotting. We examined the effects of acute i.c.v. injection of chemerin-9 on serum adrenaline by a high performance liquid chromatography. In the control siRNA-treated rats, chemerin-9 significantly increased mean BP, which reached a peak at 2 to 4 min after injection. On the other hand, in the CMKLR1 siRNA-treated rats, chemerin-9 did not affect the mean BP. Protein expression of CMKLR1 specifically in subfornical organ (SFO) and paraventricular nucleus (PVN) from the CMKLR1 siRNA-treated rats decreased compared with the control siRNA-treated rats. In the control siRNA-treated rats, chemerin-9 increased serum adrenaline level. On the other hand, in the CMKLR1 siRNA-treated rats, chemerin-9 did not affect the serum adrenaline level. Further, pretreatment with prazosin, an α-adrenaline receptor blocker, significantly prevented the pressor responses induced by chemerin-9. In summary, we for the first time demonstrated that chemerin-9 stimulates the sympathetic nerves via CMKLR1 perhaps expressed in SFO and PVN, which leads to an increase in systemic BP. [ABSTRACT FROM AUTHOR]

BPA, one of the environmental endocrine disruptors, and fructose, reason of liver steatosis which is frequently encountered in the daily diet, contribute to the formation of metabolic syndrome (MetS). This study examines the possible effects of concurrent fructose and BPA administration on MetS and determines the effects of melatonin on this process. In the seven identified groups, a total of forty-two adult male Sprague Dawley rats were treated by following fructose, BPA, and melatonin amounts, separately and together: group 1 (control), group 2 (10% aqueous fructose), group 3 (25 mg/kg BPA), group 4 (10% fructose + 25 mg/kg BPA), group 5 (10% fructose + 20 mg/kg melatonin), group 6 (25 mg/kg BPA + 20 mg/kg melatonin), and group 7 (10% fructose + 25 mg/kg BPA + 20 mg/kg melatonin). At the end of 60 days, histochemical, immunohistochemical, and biochemical procedures were performed on liver tissue. As a result, it was seen that BPA and fructose + BPA induced morphological alteration and inflammation and increased intracellular lipid quantity and amount of collagen and reticular fibers. The percentage of apoptotic liver cells stained by annexin V-FITC/PI was lower in group 7 compared to the group 4 (p < 0,001) and also in group 6 compared to the group 3 (p = 0.014). Both BPA and fructose application caused an increase in lipid peroxidation level due to the increase of oxidative stress. Application of melatonin induced antioxidant enzyme activity and reduced lipid peroxidation level. Our results indicate that fructose and BPA administration triggered the formation of MetS, whereas melatonin healed these variations, although not entirely. [ABSTRACT FROM AUTHOR]

Chemerin is an adipocytokine having cardiovascular effects. Chemokine-like receptor 1 (CMKLR1) and chemokine (CC motif) receptor-like 2 (CCRL2) are chemerin receptors. Chemerin-9, an active fragment, causes contraction via smooth muscle CMKLR1 in isolated blood vessels. Pulmonary arterial hypertension (PAH) is a fatal disease resulting ultimately in right heart failure. To test the hypothesis that chemerin affects pulmonary artery (PA) resistance, we examined the effects of chemerin-9 on contractility of isolated PA from PAH rats. Wistar rats were injected with monocrotaline (MCT) for 2 weeks to make PAH rats (MCT rats). Control (Cont) rats received a saline injection. Chemerin-9-induced contraction of isolated intrapulmonary artery (IPA) from left lung was isometrically measured. Protein expression of CMKLR1 and CCRL2 in isolated left lung was determined by Western blotting. Localization of CMKLR1 in IPA of left lung was examined immunohistochemically. Chemerin-9-induced contraction was significantly enhanced in IPA from MCT compared with Cont rats. Protein expression of CMKLR1 was significantly elevated in isolated left lung from MCT compared with Cont rats, while protein expression of CCRL2, a decoy receptor, was significantly decreased. CMKLR1 was localized mainly in endothelium of IPA in Cont rats. The CMKLR1 expression was significantly decreased in endothelium of IPA in MCT rats, while it was significantly elevated in smooth muscle. The present study for the first time demonstrated that the enhanced chemerin-9-induced contraction of isolated IPA from MCT rats was at least partly caused by the increase of CMKLR1 in smooth muscle. [ABSTRACT FROM AUTHOR]

Visfatin is an adipocytokine with important roles in endothelial angiogenesis. Hyperbaric oxygen (HBO) has been widely used to treat various medical illness with enhanced angiogenesis. The molecular effects of HBO on visfatin under hypoxia are poorly understood. This study aimed to investigate the effect of HBO on visfatin in hypoxic human coronary arterial endothelial cells (HCAECs). HCAECs under chemical hypoxia (antimycin A, 0.01 mmol/L) were exposed to HBO (2.5 atmosphere absolute; ATA) for 2‐4 hours. Western blot, real‐time polymerase chain reaction, electrophoretic mobility shift assay, luciferase promoter activity, migration and tube formation assay, and in vitro glucose uptake were measured. Visfatin protein expression increased in hypoxic HCAECs with earlier angiotensin II (AngII) secretion and c‐Jun N‐terminal kinase (JNK) phosphorylation, which could be effectively suppressed by the JNK inhibitor (SP600125), AngII antibody or AngII receptor blocker (losartan). In hypoxic HCAECs, HBO further induced earlier expression of visfatin and AngII. Hypoxia significantly increased DNA‐protein binding activity of hypoxia‐inducible factor‐1α (HIF‐1α) and visfatin. Hypoxia, hypoxia with HBO and exogenous addition of AngII also increased promoter transcription to visfatin; SP600125 and losartan blocked this activity. In HCAECs, glucose uptake, migration and tube formation were increased in the presence of hypoxia with HBO, but were inhibited by visfatin small interfering RNA, SP600125 and losartan. In conclusion, HBO activates visfatin expression and angiogenesis in hypoxic HCAECs, an effect mediated by AngII, mainly through the JNK pathway. [ABSTRACT FROM AUTHOR]

This study aimed to assess the clinicopathological significance of serum levels and endometrium tissue expression of visfatin in polycystic ovary syndrome (PCOS) patients. A total of 80 PCOS patients and 80 matching controls were included in this study. We analyzed the relationship between the expression of visfatin in endometrium and clinicopathological characteristics in PCOS patients. The correlation between the expression of visfatin and p-Akt, Akt, p-ERK1/2, and ERK1/2 in PCOS tissues was evaluated as well. Visfatin expression in PCOS endometrial tissues were significantly higher than those in controls (p =.001). The expression of phosphorylation of Akt and ERK1/2 were significantly higher in PCOS endometrium tissues compared to controls (p <.05). Moreover, a high expression of tissue visfatin in PCOS tissues was positively correlated with the expression of p-Akt (p =.015), and p-ERK1/2 (p =.013). Western blotting revealed that protein expression of visfatin in PCOS patients with endometrial hyperplasia and cancer was higher than that in patients with normal endometrium tissues, and the difference was statistically significant (p =.027). The expression of p-Akt (p =.018) and p-ERK1/2 (p =.035) in PCOS patients with endometrial hyperplasia and cancer was significantly higher than that in patients with normal endometrium tissues. Visfatin may be a potential biomarker for endometrial malignant transformation in PCOS patients. [ABSTRACT FROM AUTHOR]

Omentin-1, a 34-kDa protein, has been demonstrated to be associated with colorectal cancer (CRC). Epidemiological and clinical studies have indicated that the levels of circulating omentin-1 are significantly increased in patients with CRC, but the cause of the high omentin-1 levels and whether CRC cells express this adipokine have not been determined. In the present study, human colorectal carcinoma and para-carcinoma tissues were collected from 24 patients with CRC. In addition, SW480 and HCT116 colon cancer cells were cultured in vitro. The expression and localization of omentin-1 protein in human CRC and para-carcinoma tissues were determined by immunohistochemistry. The mRNA and protein expression levels of omentin-1 in human CRC and para-carcinoma tissues were detected by reverse transcription-quantitative PCR (RT-qPCR) and western blotting, respectively. In addition, omentin-1 mRNA expression levels in SW480 and HCT116 cell lines were detected by RT-qPCR. Since SW480 cells exhibited higher omentin-1 mRNA levels compared with those of HCT116 cells, SW480 cells were selected for further experiments. The expression of omentin-1 protein in the supernatant and lysate of SW480 cells obtained at 6, 12, 24 and 48 h was determined by ELISA. The immunohistochemistry results demonstrated that the positive expression of omentin-1 protein was mainly located in the cytoplasm of cancer cells in human CRC tissues. The mRNA and protein expression levels of omentin-1 in the CRC tissues were higher compared with those in para-carcinoma tissues. The expression levels of omentin-1 were detected in the cell lysate and supernatant of SW480 cells; the expression level of omentin-1 protein in the cell lysate was higher compared with that in the supernatant. These results indicated that SW480 cells secret and express the adipokine omentin-1 endogenously. Omentin-1 may serve its potential carcinogenetic role in CRC through endocrine, autocrine and paracrine pathways. [ABSTRACT FROM AUTHOR]

Obesity is a low-grade systemic inflammatory disease involving adipocytokines. As though Anmyungambi decoction (AMGB) showed significant improvement on obesity in a clinical trial, the molecular mechanism of AMGB in obesity remains unknown. Therefore, we explored the potential mechanisms of action of AMGB on obesity through network pharmacological approaches. We revealed that targets of AMGB are significantly associated with obesity-related and adipocyte-elevated genes. Evodiamine, berberine, genipin, palmitic acid, genistein, and quercetin were shown to regulate adipocytokine signaling pathway proteins which mainly involved tumor necrosis factor receptor 1, leptin receptor. In terms of the regulatory pathway of lipolysis in adipocytes, norephedrine, pseudoephedrine, quercetin, and limonin were shown to affect adrenergic receptor-beta, protein kinase A, etc. We also found that AMGB has the potentials to enhance the insulin signaling pathway thereby preventing type II diabetes mellitus. Additionally, AMGB was discovered to be able to control not only insulin-related proteins but also inflammatory mediators and apoptotic regulators and caspases, hence reducing hepatocyte injury in nonalcoholic fatty liver disease. Our findings help develop a better understanding of how AMGB controls obesity.

Abstract Background The role of vaspin in the pathogenesis of stable coronary artery disease (SCAD) have been repeatedly addressed in clinical studies. However, from the point of view of clinical practice, the results of earlier studies are still inconclusive. Methods The data of 106 SCAD patients who received coronary angiography and 85 coronary artery disease-free controls were collected and analysed. The patients were divided into subgroups according to their pre-test probability (PTP) and according to the result of coronary angiography. Fasting vaspin concentrations were compared between subgroups of SCAD patients and between target group and controls. The effect of age and smoking on the result of coronary angiography was compared to the effect of vaspin using the binomial regression. Results We did not find significant difference in vaspin level between target group and controls. Unless the pre-test probability was taken into account, we did not find vaspin difference in the target group, when dividing patients on the basis of presence/absence of significant coronary stenosis. In the subgroup of SCAD patients with PTP between 15% – 65%, those with significant coronary stenoses had higher mean vaspin concentration (0,579 ± 0,898 ng/ml) than patients without significant stenoses. (0,379 ± 0,732 ng/ml) (t = −2595; p = 0,012; d = 0,658; 1-β = 0,850). Age, smoking status and vaspin significantly contributed to the HSCS prediction in binomial regression model in patients with low PTP (OR: 1.1, 4.9, 8.7, respectively). Conclusion According to our results, vaspin cannot be used as an independent marker for the presence of CAD in general population. However, our results indicate that measuring vaspin in SCAD patients might be clinically useful in patients with PTP below 66%.

Background: Periodontitis is a chronic inflammatory disease caused by bacterial infection in the periodontal support tissue. Visfatin, a hormone secreted mainly by adipocytes and macrophages, plays an important role in immune regulation and defense. Although studies have indicated that patients with periodontitis have significantly high serum and gingival crevicular fluid levels of visfatin, the relationship between this adipocytokine and periodontal disease remains unclear., Aim: The aim of this study was to systematically evaluate the association between visfatin levels and periodontitis., Methods: The PubMed, Web of Science, ScienceDirect, EBSCO, and Wiley Online Library databases were searched for potential studies, using "periodontitis" and "visfatin" as the keywords in the title and abstract search fields. Standardized mean difference (SMD) values with corresponding 95% confidence intervals (CIs) were determined from the results of this meta-analysis., Results: In total, 22 articles involving 456 patients with periodontitis and 394 healthy individuals (controls) were included in the meta-analysis. Visfatin levels were significantly higher in the patients with periodontitis than in the healthy individuals (SMD: 3.82, 95% CI [3.01-4.63]). Moreover, the visfatin levels were significantly lowered after periodontitis treatment (SMD: -2.29, 95% CI [-3.33 to -1.26])., Conclusion: This first-ever meta-analysis comparing visfatin levels between patients with periodontitis and healthy individuals suggests that this adipocytokine can be a diagnostic and therapeutic biomarker for periodontal disease., Competing Interests: The authors declare that they have no competing interests., (© 2024 Li et al.)

Background: In addition to glucose metabolism, adipocytokine Nicotinamide phosphoribosyltransferase (Nampt) has been proposed as a multifunctional protein involved in insulin resistance. Insulin resistance always occurs before the onset of type 2 diabetes mellitus (T2DM) and damages the cognition of T2DM patients very early.Objective: We aimed to investigate the role and potential clinical value of Nampt in early cognitive decline of T2DM.Methods: A total of 195 Chinese T2DM patients were enrolled and divided into a mild cognition impairment (MCI) group and a healthy cognition group according to Montreal Cognitive Assessment (MoCA) score. Their cognitive function was extensively assessed. The plasma level of Nampt was measured via enzyme-linked immunosorbent assay.Results: In the MCI group (n = 78, MoCA < 26), the plasma level of Nampt was significantly higher than the controls (p < 0.01). After adjusting for age, sex, and level of education, Nampt levels were negatively associated with most of the cognitive domains forecasting hypomnesia (all p < 0.007). Nevertheless, hierarchical regression analysis further revealed that Nampt was an independent risk factor of MCI in Chinese T2DM patients (all p < 0.05), including Logic Memory Test (β= -0.31, p < 0.01), Auditory Verbal Learning Test delayed recall (β= -0.26, p < 0.01), and so on, which represent memory function. Correlation analysis showed that Nampt related to insulin resistance (HOMA-IR), glycosylated hemoglobin (HbA1c), and lipid levels (all p < 0.05).Conclusions: We found that higher plasma level of Nampt presages memory dysfunction in MCI in Chinese T2DM patients. Further studies are necessary to confirm its scanning and prognosis prediction value of the disease clinically. [ABSTRACT FROM AUTHOR]

Background/aim: Recent data draw attention to the effect of body composition, insulin resistance, and adipocytokines to acne vulgaris (AV) development. The aim of this study was to assess the association of AV with insulin resistance and adipocytokine levels and to evaluate the effect of isotretinoin on insulin resistance and adipocytokine levels. Materials and methods: In 29 AV patients and 29 healthy volunteers, body mass index (BMI) and body fat mass (BFM), lipid, adiponectin, leptin, resistin, retinol binding protein-4 (RBP4), and insulin levels were measured and insulin resistance was assessed by HOMA-IR index in serum samples taken twice from patients before and after isotretinoin treatment. Results: In AV patients, pretreatment HOMA-IR and adipocytokine levels were not found to correlate with disease severity. With five months of isotretinoin treatment, higher HOMA-IR values were found (P = 0.028). Isotretinoin therapy maintained lower mean resistin levels (P = 0.016), higher mean RBP4 levels (P = 0.040), but not affected the mean adiponectin and leptin levels (P = 0.113, P = 0.125, respectively). Conclusions: All data suggests that five months of isotretinoin therapy in AV patients causes insulin resistance and the increase in insulin resistance is not dependent on age, BMI, BFM, and lipid levels of these patients. [ABSTRACT FROM AUTHOR]

Sodium-glucose transporter 2 (SGLT2) inhibitors were shown to decrease mortality from cardiovascular diseases in the EMPA-REG trial. However, the effects of empagliflozin (EMPA) for cardiac arrhythmia are not yet clarified. A total of 20 C57BL/6J mice were divided into four groups: (1) The control group were fed standard chow, (2) the metabolic syndrome (MS) group were fed a high-fat diet, (3) the empagliflozin (EMPA) group were fed a high-fat diet and empagliflozin 10 mg/kg daily, and (4) the glibenclamide (GLI) group were fed a high-fat diet and glibenclamide 0.6 mg/kg daily. All mice were sacrificed after 16 weeks of feeding. H9c2 cells were treated with adipocytokines from the pericardial and peripheral fat from the study groups. The delayed-rectifier potassium current (IK) and L-type calcium channel current (ICa,L) were measured by the whole-cell patch clamp techniques. Adipocytokines from the peripheral and pericardial fat tissues of mice with MS could decrease the IK and increase the ICa,L of cardiomyocytes. After treating adipocytokines from pericardial fat, the IK in the EMPA and GLI groups were significantly higher than that in the MS group. The IK of the EMPA group was also significantly higher than the GLI group. The ICa,L of the EMPA and GLI groups were significantly decreased overload compared with that of the MS group. However, there was no significant difference of IK and ICa,L among study groups after treating adipocytokines from peripheral fat. Adipocytokines from pericardial fat but not peripheral fat tissues after EMPA therapy attenuated the effects of IK decreasing and ICa,L increasing in the MS cardiomyocytes, which may contribute to anti-arrhythmic mechanisms of sodium-glucose transporter 2 (SGLT2) inhibitors.

Background: Oxidative stress and alteration of lipid profile due to obesity and overweight is a major risk factor for atherosclerotic plaque or coronary artery disease. Because of antioxidant and lipid lowering potential of saffron, this study investigated weight alteration, lipid profiles, and insulin resistance index in high-calorie diet rats treated with aqueous extract of saffron stigma and petal. Methods: Forty Sprague-Dawley male rats were randomly divided into 8 groups including healthy control, high-fat diet control, nicotinic acid treated, Anethum graveolens treated, and saffron stigma and petal treated groups. Rats received a high-calorie diet for 16 weeks. For treatment, aqueous extract of saffron stigma (40 and 80 mg/kg) and petal (50 and 100 mg/kg) was used once daily for 4 weeks. Afterward, lipid profile, oxidative stress status, and insulin and adiponectin levels were measured using desired kits. Results: There was a significant decrease in the mean weight of the groups receiving saffron stigma and petal compared to control group (P < 0.05). The increased level of insulin hormone in obese group was improved in treated groups especially in the case of saffron stigma. Also, the decreased level of adiponectin was recovered in treated groups. An improvement was seen in oxidative stress markers and lipid profiles in treated groups compared to obesity pair. Conclusions: In this study, a remarkable antioxidant and lipid lowering potential was detected for saffron stigma, which could improve insulin resistance in obese rats. Therapeutic and protective effect of saffron is mainly related to its richness in phenolic compounds. Saffron stigma compared with petal had more notable effect, which could and should be mentioned in pharmaceutical studies.

Traditionally, it is believed that white adipose tissues serve as energy storage, heat insulation, and mechanical cushion, whereas non-shivering thermogenesis occurs in brown adipose tissue. Recent evidence revealed that adipose tissue secretes many types of cytokines, called as adipocytokines, which modulate glucose metabolism, lipid profile, appetite, fibrinolysis, blood pressure, and inflammation. Most of the arteries are surrounded by perivascular adipose tissue (PVAT). PVAT has been thought to be simply a structurally supportive tissue for vasculature. However, recent studies showed that PVAT influences vasodilation and vasocontraction, suggesting that PVAT regulates vascular tone and diameter. Adipocytokines secreted from PVAT appear to have direct access to the adjacent arterial wall by diffusion or via vasa vasorum. In fact, PVAT around atherosclerotic lesions and mechanically-injured arteries displayed inflammatory cytokine profiles, suggesting that PVAT functions to promote vascular lesion formation. Many clinical studies revealed that increased accumulation of epicardial adipose tissue (EAT), which surrounds coronary arteries, is associated with coronary artery disease. In this review article, we will summarize recent findings about potential roles of PVAT in the pathogenesis of atherosclerosis, particularly focusing on a series of basic and clinical studies from our laboratory.

BackgroundMetabolic health is an emerging concept that is highly correlated with various metabolic complications, and adipocytokines have been causally linked to a wide range of metabolic diseases. Thus, this study compared serum adipocytokine levels according to metabolic health and obesity status.MethodsFour hundred and fifty-six nondiabetic subjects (mean age, 40.5 years) were categorized into four groups according to metabolic health and obesity status: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUHNO), and metabolically unhealthy obese (MUHO). Being metabolically healthy was defined as the presence of fewer than two of the following five metabolic abnormalities: high blood pressure, high fasting blood glucose, high triglyceride, low high density lipoprotein cholesterol, and being in the highest decile of the homeostatic model assessment of insulin resistance index. Obesity status was assessed using body mass index (BMI), with obesity defined as a BMI higher than 25 kg/m2. Levels of serum interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor α (TNF-α), and adipocyte fatty acid binding protein (A-FABP) were also evaluated.ResultsOf the 456 subjects, 247 (54.2%) were in the MHNO group, 66 (14.5%) were in the MHO group, 66 (14.5%) were in the MUHNO group, and 77 (16.9%) were in the MUHO group. There were no significant differences in IL-6 or MCP-1 levels among the groups, but levels of TNF-α and A-FABP were significantly higher in the MUHNO group compared to the MHNO group.ConclusionHigh TNF-α and A-FABP levels are significantly associated with metabolically unhealthiness in nonobese Korean individuals.

A 65‐day growth trial was conducted to investigate the effects of dietary conjugated linoleic acid (CLA) on growth performance, tissue adipocytokine levels and lipid metabolism of grass carp. Seven isonitrogenous and isolipidic diets were formulated as follows: 0 (control), 5 (CLA5), 10 (CLA10), 15 (CLA15), 20 (CLA20), 25 (CLA25) and 30 (CLA30) g/kg CLA. Results showed that incorporating as low as 25 g/kg CLA in the diet significantly decreased the growth of grass carp. The liver lipid content in fish fed with CLA15 to CLA30 significantly decreased. The leptin and resistin levels in liver of fish fed with CLA5 to CLA30 diets significantly increased. The mRNA expression levels of fatty acid synthase (FAS) and triacylglycerol lipase (TGL) in liver of fish fed with CLA5 to CLA30 and CLA10 to CLA30 diets also significantly decreased, respectively. In summary, the lipid‐lowering effects in grass carp liver were induced by the supplementation of 15–20 g/kg CLA, but its growth remained unaffected. Moreover, the lipid‐lowering effects of CLA on grass carp could also be modulated both by adipocytokine levels and by the expression of genes involved in lipid metabolism in tissues. [ABSTRACT FROM AUTHOR]

Abstract Sarcopenia is associated with loss of muscle mass and function as well as oxidative stress, chronic low-grade inflammatory status, and adipocytokine dysfunction. It has been reported that sarcopenia can be attenuated by exercise training. The purpose of this study was to evaluate whether long-term high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) protocols could differentially modulate changes in body composition, physical performance, inflammatory parameters, and adipocytokines in fat tissues and serum, as well as oxidative parameters and insulin-like growth factor 1 (IGF-1) levels in skeletal muscle tissue of aged rats. Middle-aged (18-month-old) female Sprague Dawley rats (n = 36) were subjected to 8 months of MICT (26–m MICT) or HIIT (26–m HIIT) treadmill training (45 min, 5 times per week), and the results were compared with those of age-matched sedentary controls (26–m SED); 8-month-old (8–m SED) and 18-month-old (18–m SED) rats served as aging sedentary controls. Body composition parameters; physical performance; serum and skeletal muscle oxidative stress parameters; levels of IGF-1, a serum and fat tissue inflammatory marker; adipocytokine (leptin, adiponectin) levels; and plasma glucose and lipid metabolism-related parameters were analyzed among the five groups. The percent fat and body fat to lean mass ratio increased as a main effect with age, whereas 26–m HIIT but not 26–m MICT attenuated these alterations. The 26–m HIIT group showed a larger improvement in grip strength compared to that of 26–m MICT, with a similar increase in inclined plane performance, maximum running speed, and exhaustion over time as compared with the 26–m SED group. Notably, the 26–m HIIT group showed lower high-sensitivity C-reactive protein levels and higher IL-10 in serum compared with those of the 26–m SED and 26–m MICT groups. Both exercise protocols promoted increased skeletal muscle IGF-1 and decreased serum IGF-1 and adiponectin relative to those in the 26–m SED group, whereas only 26–m HIIT dampened the age-related decrease in plasma free fatty acids and increased serum leptin, along with providing lower fat tissue leptin as compared with that in the 26–m SED group. Moreover, the 26–m HIIT group showed lower serum and skeletal muscle malonylaldehyde and skeletal muscle 8-hydroxydeoxyguanosine (8-OHdG) levels than those in the 26–m MICT group, albeit similar decreases in serum and skeletal muscle 4-hydroxynonenal and serum 8-OHdG and increases in skeletal muscle superoxide dismutase 2 activity. In conclusion, HIIT initiated late in life exhibited greater beneficial effects in ameliorating aged-related elevations in oxidative stress and inflammation, as well as dysfunction of circulating adipocytokine levels, than a volume-matched MICT program. HIIT may therefore contribute to improvements in body composition and physical performance changes associated with aging. Highlights • Aged rats showed oxidative stress, inflammation, and adipocytokine dysfunction. • Long-term high intensity interval training (HIIT) improved these and grip power. • Volume-matched moderate intensity continuous training only improved endurance. • HIIT is a promising strategy to improve body performance and status in the elderly. [ABSTRACT FROM AUTHOR]

Highlights • Circulating chemerin is independently associated with NSCLC risk. • Chemerin correlates with metabolic, tumor, inflammatory and hemostatic parameters. • Hemostatic parameters are independent predictors of circulating chemerin in NSCLC. • Circulating chemerin presents a modest discriminative ability for NSCLC diagnosis. • Chemerin is at the intersection of inflammatory, hemostatic and metabolic networks. Abstract Objectives Chemerin is an emerging adipocytokine at the intersection of inflammation, chemotaxis, thrombosis, fibrinolysis and metabolism. Our aims were 1) to explore circulating chemerin in resectable non-small cell lung cancer (NSCLC) taking into account its several interfaces; 2) to study its diagnostic potential; and 3) to assess its associations with clinicopathological features of NSCLC. Materials and Methods In a large case-control study, serum chemerin, insulin resistance and lipid parameters, classic adipocytokines, inflammatory, coagulation, fibrinolysis and tumor biomarkers were determined in 110 consecutive patients with resectable NSCLC and 110 healthy controls matched on age (± 5 years), gender and date of blood draw (± 1 month). Results NSCLC cases exhibited significantly elevated circulating chemerin compared to controls (p < 0.001). In NSCLC cases, chemerin was positively associated with Homeostasis model assessment score of insulin resistance (HOMA-IR), fibrinogen, plasminogen activity, tumor and inflammatory biomarkers, adiponectin, number of infiltrated lymph nodes and NSCLC stage. In control participants, circulating chemerin was positively correlated with somatometric, metabolic, lipid, hemostatic and inflammatory biomarkers, and leptin. Serum chemerin was independently associated with NSCLC, above and beyond NSCLC risk factors (OR: 2.20, 95% CI: 1.09–4.40, p = 0.03). In cases, hemostatic parameters (platelet count and plasminogen activity), HOMA-IR, CYFRA 21-1, creatinine and plant food consumption emerged as independent predictors of circulating chemerin (p < 0.05). Serum chemerin greater than 220 μg/L (cut-off point) yielded a sensitivity and a specificity of 63% and 91.8% respectively with a modest discriminative ability (AUC = 0.72, 95% C.I. 0.64-0.79) for the diagnosis of NSCLC. Conclusion Chemerin may represent a potentially useful biomarker in NSCLC integrating tumor-promoting networks, inflammatory and hemostatic mechanisms, and cancer-related metabolic pathways. More preclinical, prospective and longitudinal studies highlighting the pathogenetic role of chemerin in NSCLC are needed to corroborate and extend these data. [ABSTRACT FROM AUTHOR]

We explored the effects of RNA interference‐mediated silencing of TLR4 gene on expressions of adipocytokines in obstructive sleep apnea hyponea syndrome (OSAS) with hypertension in a rat model. Systolic blood pressure of caudal artery and physiological changes were observed when establishing rat models of OSAS with hypertension. Mature rat adipocytes were induced from separated and cultured primary rat adipocytes. To transfect rat mature adipocytes, TLR4 siRNA group and negative control (NC) siRNA group were established. Expressions of TLR4 mRNA of adipocytes were examined after silenced by siRNA by quantitative real‐time polymerase chain reaction (qRT‐PCR). By enzyme‐linked immunosorbent assay (ELISA), expressions of inflammatory cytokines, and adipocytokines of adipocytes were detected. Blood pressure in rat caudal artery was higher in the intermittent hypoxia group than that of the blank control group by 29.87 mmHg, and cardiocytes in the former group showed physiological changes, which indicated successful establishment of rat models of OSAS with hypertension. Red particles could be seen in mature rat adipocytes when stained with Oil Red O. Transfection of TLR4 mRNA was significantly suppressed in the TLR4 siRNA group, which didn't happen in the untransfected control group. Rats in the TLR4 siRNA group had significantly reduced expressions of such inflammatory cytokines as interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), and tumor necrosis factor‐α (TNF‐α) and such adipocytokines as visfatin, adiponectin (ADN), and leptin than those in the untransfected control group. RNA interference‐mediated silencing of TLR4 gene could regulate occurrence and development of OSAS with hypertension in rats by downregulating expressions of adipocytokines. [ABSTRACT FROM AUTHOR]

Background: The impaired adipocytes secrete factors observed in diabetes contribute to insulin resistance. The purpose of the present study was to compare the effects of high-intensity interval versus moderate intensity combined resistance and aerobic training on some adipokines related to insulin resistance (interleukin-6 [IL-6], apelin, and monocyte chemoattractant protein 1 (MCP-1)) in women with type 2 diabetes. Methods: Fifty two females with type 2 diabetes (aged 45 - 60 years, the HbA1C value of 6.5% or above, and fasting blood glucose 126 mg/dL (7.0 mmol/L)) were assessed for eligibility. The participants were assigned to a HIIT group (n = 17), a combined resistance and aerobic training group (n = 17), and a control group (n = 18) randomly. The exercises included 10 weeks of combined training and HIIT. Results: TNF-concentrations changed significantly in the HIIT (P = 0.001) and combined training (P = 0.015) groups. The same test revealed that the differences were significant for the IL-6 in the HIIT (P < 0.000) and combined training (P < 0.000) groups. Data also showed significant differences in MCP-1 and IL-6 levels in the HIIT and combined resistance and aerobic training groups (P < 0.05). In addition, there were no significant changes in apelin in both groups after 10 weeks (P > 0.05). The ANCOVA test showed no significant differences in apelin (F = 0.511, P = 0.12). Conclusions: The results highlight that exercise training, independent of the mode of training, is an effective strategy to improve some adipokines related to insulin resistance in women with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Glycine supplementation has been reported to enhance white-fat loss and improve sensitivity to insulin in animals with obesity or type 2 diabetes. However, the underlying mechanisms responsible for the beneficial effects of glycine remain largely unknown. The purpose of this study was to test the hypothesis that glycine regulates adipocyte differentiation, adipogenesis, and lipolysis, therefore, contributing to white-fat reduction. 3T3-L1 pre-adipocytes were induced to differentiate into adipocytes in the presence of glycine (0, 0.25, 1.0, and 2.0 mmol/L) or resveratrol (50 or 100 μmol/L, served as a positive control) during the differentiation process. Hela and HepG2 cells cultured with oleic acid to induce lipid accumulation in the presence of glycine (0, 1.0, and 2.0 mmol/L) or 10 μmol/L isoproterenol (served as a positive control) for 24 h. Intracellular lipid accumulation, intracellular triglycerides, lipid droplets’ diameters of mature adipocytes, mRNA, and protein levels of genes involved in the adipogenesis and lipolysis were analyzed. Isobutylxanthine-dexamethasone-insulin (MDI)-induced adipogenesis in 3T3-L1 cells were blocked by resveratrol, but not by glycine, as shown by decreased lipid contents, reduced diameters of lipid droplets, decreased protein abundances for peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), as well as increased protein abundance of peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), critical transcriptional factors that regulates adipogenesis. However, the mRNA levels of adiponectin and interleukin-10 (IL-10), two adipose-derived adipocytokines with anti-inflammatory effects, were greatly enhanced (P < 0.05) by 2 mmol/L glycine. Compared with non-treated controls, 10 μmol/L isoproterenol significantly decreased (P < 0.05) the intracellular lipid and triglyceride contents induced by oleic acid in Hela and HepG2 cells. mRNA level of fatty acid synthase (FASN), a gene involved in fatty acid synthesis, was significantly reduced (P < 0.05), while that for ATGL (adipose triglyceride lipase) and HSL (hormone-sensitive lipase), genes involved in lipolysis were significantly enhanced (P < 0.05) by isoproterenol. However, oleic acid induced the accumulation of intracellular triglyceride and lipid contents were not affected by glycine. In conclusion, glycine exposure enhanced the mRNA levels of adipose-derived adiponectin and IL-10 without affecting adipogenesis and lipolysis in 3T3-L1 adipocytes. These findings provide a possible explanation for the anti-obesity and anti-diabetic effects of glycine that were previously reported in animal models. More studies are needed to uncover the underlying mechanisms responsible for this regulatory effect of glycine on anti-inflammatory adipocytokines expression in both in vitro and in vivo models. [ABSTRACT FROM AUTHOR]

A substantial number of studies have revealed that a growing list of cancers might be influenced by obesity. In this regard, one of the most prominent and well-characterized cancers is breast cancer, the leading cause of cancer death among women. Obesity is associated with an increased risk for the occurrence and development of breast cancer particular in postmenopausal women. Moreover, the relationship between adiposity and breast cancer risk is complex, with associations that differ depending on when body size is assessed (eg, premenopausal vs postmenopausal obesity) and when breast cancer is diagnosed (ie, premenopausal vs postmenopausal disease). Obesity is mainly due to excessive fat accumulation in the regional tissue. Adipocytes in obese individuals produce endocrine, inflammatory, and angiogenic factors to affect adjacent breast cancer cells. Adipocytokines, are biologically active polypeptides that are produced either exclusively or substantially by adipocytes, play a critical and complex role, and act by endocrine, paracrine, and autocrine pathways in the malignant progression of breast cancer. Furthermore, the increased levels of leptin, resistin, and decreased adiponectin secretion are directly associated with breast cancer development. And there are also many studies indicating that adipocytokines could mediate the survival, growth, invasion, and metastasis of breast cancer cells by different cellular and molecular mechanisms to reduce the survival time and prompt the malignancy. In present review, we discuss the correlations between several adipocytokines and breast cancer cells in obesity as well as the underlying signaling pathways to provide the novel ideas for the prevention and treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Traditionally, it is believed that white adipose tissues serve as energy storage, heat insulation, and mechanical cushion, whereas non-shivering thermogenesis occurs in brown adipose tissue. Recent evidence revealed that adipose tissue secretes many types of cytokines, called as adipocytokines, which modulate glucose metabolism, lipid profile, appetite, fibrinolysis, blood pressure, and inflammation. Most of the arteries are surrounded by perivascular adipose tissue (PVAT). PVAT has been thought to be simply a structurally supportive tissue for vasculature. However, recent studies showed that PVAT influences vasodilation and vasocontraction, suggesting that PVAT regulates vascular tone and diameter. Adipocytokines secreted from PVAT appear to have direct access to the adjacent arterial wall by diffusion or via vasa vasorum. In fact, PVAT around atherosclerotic lesions and mechanically-injured arteries displayed inflammatory cytokine profiles, suggesting that PVAT functions to promote vascular lesion formation. Many clinical studies revealed that increased accumulation of epicardial adipose tissue (EAT), which surrounds coronary arteries, is associated with coronary artery disease. In this review article, we will summarize recent findings about potential roles of PVAT in the pathogenesis of atherosclerosis, particularly focusing on a series of basic and clinical studies from our laboratory. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR), the most common cause of irreversible blindness in working-age adults, results in central vision loss that is caused by microvascular damage to the inner lining of the back of the eye, the retina. The aim of this work was to assess the temporal relationships between angiopoietin-like protein-4 (ANGPTL-4), a novel adipocytokine factor, and diabetic retinal inflammation and microvascular dysfunction. The downstream pathway(s) and upstream mediator(s) of ANGPTL-4 were then determined under high glucose (HG) conditions. Diabetic rats and control animals were randomly assigned to receive hypoxia inducible factor-1 alpha (HIF-1α) blockade (doxorubicin or shRNA) or vehicle for 8 weeks. Human retinal microvascular endothelial cells (HRMECs) were incubated with normal or high glucose, with or without blockade or recombinant proteins, for ANGPTL-4, HIF-1α, and vascular endothelial growth factor (VEGF). The levels of ANGPTL-4, profilin-1, HIF-1α, VEGF, interleukin 1 beta (IL-1β), IL-6, and intercellular adherent molecule 1 (ICAM-1) in the rat retinas and HRMEC extracts were examined by Western blotting and real-time RT-PCR. The levels of ANGPTL-4, profilin-1, HIF-1α, and VEGF protein and mRNA were significantly higher in the diabetic rats and HG-exposed HRMECs. ANGPTL-4 was a potent modulator of increased inflammation, permeability, and angiogenesis via activation of the profilin-1 signaling pathway. Our results showed that ANGPTL-4 upregulation was induced by HG, which was dependent on HIF-1α activation that was also triggered by HG, both in vivo and in vitro . Our results suggest that targeting ANGPTL-4, alone or in combination with profilin-1, may be an effective therapeutic strategy and diagnostic screening biomarker for proliferative diabetic retinopathy and other vitreous-retinal inflammatory diseases. [ABSTRACT FROM AUTHOR]

Objective (s):Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder, primarily targeting the synovium and articular cartilage that leads to joint damage. Recent reports have suggested the role of adipocytokines in mediating joint damage; however it still is a matter of debate. The purpose of this study was to evaluate the association between serum values of adiopocytokines (leptin, visfatin) and radiographic joint damage in patients with RA. Materials and Methods:Fifty-four patients diagnosed with RA, based on Revised ACR Criteria 2010, with 1-5 year disease duration since diagnosis, were enrolled. Twenty-nine of patients had erosion in radiographic studies and 25patients had no erosion. Radiographic joint damages were defined according to Larsen Score. Additionally, serum levels of adipocytokines were measured and cross-sectional associations with radiographic damage were explored, adjusting for pertinent confounders. Results:The serum level of visfatin were significantly higher in patients with radiographic joint damage compared with patients with no joint damage (P=0.013). This difference remained significant after adjustment for C-reactive protein levels (P=0.008), but not after adjustment for disease duration (P=0.247). The mean leptin serum levels were not different between these two groups (P=0.903). There was a positive correlation between leptin levels and BMI (r=0.494, P

Background: Laparoscopic sleeve gastrectomy (LSG) has wide-ranging positive effects on adipocytokine metabolism, bile acid profile, and chronic low-grade inflammation related to obesity. However, the early temporal changes in these markers following LSG have not been well investigated. This study aimed to evaluate the early effects of LSG on adipocytokines, bile acid profile, and inflammatory markers. Methods: This was a nonrandomized prospective study examining morbidly obese Japanese patients undergoing LSG. Serial measurements of leptin, adiponectin, bile acids, fibroblast growth factor (FGF)-19, and inflammatory markers were performed preoperatively and 1 and 6 months after LSG. Results: The study included ten patients (five females) with a mean age of 48.8 years and BMI 40.9 kg/m. At baseline, 90% of the patients had T2DM, 70% had dyslipidemia, and 90% had hypertension. Patients lost 5.1 kg/m BMI at 1 month and 10.1 kg/m BMI at 6 months. The leptin levels sharply decreased, and FGF-19 increased significantly as early as 1 month postoperatively. Adiponectin levels showed an increasing trend at 1 month and a significant increase at 6 months. A significant decrease in high-sensitivity CRP and plasminogen activator inhibitor-1 was observed at 6 months. No significant changes were observed in interleukin (IL)-6, IL-8, tumor necrosis factor-α, serum amyloid A protein, or monocyte chemotactic protein-1 throughout the study. Conclusions: LSG improved the secretion of adipocytokines, increased FGF-19 secretion soon after surgery, and slowly ameliorated inflammation related to obesity through significant weight loss. [ABSTRACT FROM AUTHOR]

Visceral adipose tissue-derived serine protease inhibitor (vaspin), a recently identified adipocytokine, inhibits inflammation, migration, and apoptosis of vascular cells. We have recently demonstrated that chronic administration of vaspin to spontaneously hypertensive rats partly prevents systemic hypertension through inhibiting inflammation and remodeling of vascular wall. Pulmonary arterial (PA) hypertension (PAH) is caused by PA remodeling, contractile dysfunction, and inflammatory responses. We tested the hypothesis that vaspin could prevent development of PAH in animal model. PAH was induced by a single intraperitoneal injection of monocrotaline (MCT; 60 mg/kg), and vaspin (1 μg/kg/day) was treated for 14 days from the day of MCT injection. PA pressure and contractile reactivity of isolated intrapulmonary artery (IPA) were measured. Using isolated lung tissues, IPA wall thickness and fibrosis, matrix metalloproteinase (MMP) activity, and reactive oxygen species (ROS) generation were examined. For in vitro study, after rat PA smooth muscle cells (PASMCs) were stimulated with interleukin (IL)-1β (10 ng/ml, 48 h) in the presence of vaspin (5 ng/ml, 30 min), MMP activity and ROS generation were examined. Vaspin significantly attenuated MCT-induced rise in PA pressure, while it had no influence on impairment of relaxing function in IPA. Vaspin significantly prevented MCT-induced IPA fibrosis but not hypertrophy. Vaspin significantly inhibited MCT-induced ROS generation and MMP-2 activation in lung tissues. In addition, vaspin significantly inhibited IL-1β-induced ROS generation and MMP-2 activation in PASMCs. In summary, we for the first time demonstrate that vaspin prevents MCT-induced PAH at least in part via inhibiting ROS/MMP-2/fibrosis pathway. [ABSTRACT FROM AUTHOR]

Background and Objectives: Obesity has become a public health problem and is a cause of some preventable illnesses. Among several methods for treating obesity, the use of food supplements is highly common. A commonly used food supplement is green coffee bean extract. The objective of this study was to evaluate the efficacy of green coffee bean extract combined with an energy-restricted diet on the body composition and serum adipocytokines in obese women.Methods and Study Design: In this randomised clinical trial, 64 obese women aged 20-45 years were selected and divided into two groups: an intervention group (receiving 400 mg green coffee bean extract for 8 weeks) and control group (receiving placebo). All participants were on an energy-restricted diet. The body composition, leptin, adiponectin, lipid profile, free fatty acids (FFAs), and fasting blood sugar were compared between the two groups.Results: We observed significant reductions in the body weight, body mass and fat mass indices, and waist-to-hip circumference ratio in both groups; however, the decrease was higher in the intervention group. Moreover, serum total cholesterol, low-density lipoprotein, leptin, and plasma free fatty acids significantly decreased in the intervention group (p<0.05) after adjustment for energy and fibre intake. The serum adiponectin concentration significantly increased in the intervention group (p<0.05).Conclusions: Green coffee bean extract combined with an energy-restricted diet affects fat accumulation and lipid metabolism and is thus an inexpensive method for weight control in obese people. [ABSTRACT FROM AUTHOR]

Fatty acid-binding protein (FABP) 4 is an adipocytokine mainly expressed in adipocyte and macrophage. Blood FABP4 is related not only to metabolic disorders including insulin resistance and atherosclerosis but also increased blood pressure. We tested the hypothesis that FABP4 plays roles in pathogenesis of hypertension development including proliferation, migration, and inflammation of vascular smooth muscle cells (SMCs) as well as contractile reactivity. FABP4 alone had no influence on proliferation, migration, and inflammation of rat mesenteric arterial SMCs, while it significantly enhanced smooth muscle contraction and increases of systolic blood pressure (SBP) induced by noradrenaline (NA). BMS-309403, an FABP4 inhibitor, significantly inhibited platelet-derived growth factor-BB-induced DNA synthesis and migration via preventing p38 and HSP27 activation. Further, BMS-309403 significantly inhibited tumor necrosis factor-α-induced expression of vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 as well as monocyte adhesion via preventing NF-κB activation. Interestingly, SMCs do not express FABP4. Long-term treatment of spontaneously hypertensive rats (SHR) with BMS-309403 significantly inhibited impaired relaxation in isolated mesenteric arteries and left ventricular hypertrophy, while it had no influence on SBP. We for the first time showed that FABP4 acutely enhances NA-induced increases of SBP possibly through the enhancement of peripheral arterial contractility. BMS-309403 prevents proliferation, migration, and inflammatory responses of SMCs, although exogenous application of FABP4 has no influence on the cellular responses. Furthermore, we demonstrated that long-term treatment with BMS-309403 partially improves the pathological conditions of SHR. These results indicate that BMS-309403 would be useful for developing a new pharmacotherapeutic agent against obesity-associated hypertension and complications. [ABSTRACT FROM AUTHOR]

Nowadays, diabetes mellitus (DM) along with its complications is considered as a fundamental problem in both developing and industrial countries, and is causing millions of people to suffer worldwide. Currently, diabetes mellitus is diagnosed traditionally or classically in the world by measuring fasting blood glucose and conducting oral glucose tolerance test. New alternatives are required for the treatment of diabetes mellitus, especially type 2 diabetes mellitus (T2DM), at its early levels due to the ineffective control of its development in patients. In recent years, by further identifying of molecular agents such as microRNAs (miRNAs), studies have focused on miRNAs in diabetes as well as in other diseases. These small non-coding RNA molecules have a significant role in the regulation of insulin gene expression and also, obesity problems. White adipose tissue, as an important tissue in obese subjects, is directly related to type 2 diabetes and its complications via synthesis of adipokines. Prevention and treatment of obesity should be noted since childhood. Our aim in this review is to briefly provide a new glance at types of potential biomarkers, which can be used as pharmacological targets for prevention and treatment of prediabetic subjects, and patients with T2DM. [ABSTRACT FROM AUTHOR]

Objective: To analyze the concentrations of nesfatin-1 in maternal and cord serum, to evaluate the expression of nesfatin-1 in subcutaneous adipose tissue (SAT) from pregnant women with gestational diabetes mellitus (GDM) and those with normal glucose tolerance (NGT). Methods: We studied a total of 50 GDM and 50 NGT subjects. The clinical features, serum nesfatin-1, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profiles were measured at the third trimester of pregnancy. The expression of nesfatin-1 in the SAT was determined by western blot. Results: Compared with the NGT group, the GDM group showed greater levels of serum nesfatin-1, adipocyte fatty acid binding protein (AFABP), and leptin; a greater level of cord blood nesfatin-1; and a higher level of expression in SAT (p < 0.05 orp < 0.01). Fasting insulin (FI) (b = 0.317,p= 0.022) and body mass index (BMI) before delivery (b = 0.367,p=0.008) were independently associated with serum nesfatin-1. Nesfatin-1 was the independent risk factor for GDM. Conclusions: The GDM group had higher levels of maternal serum and cord blood nesfatin-1, and greater nesfatin-1 expression in SAT. Nesfatin-1 is closely related to obesity and IR in pregnancy. [ABSTRACT FROM AUTHOR]

The adipocytokines and insulin-like growth factor 1 (IGF-1) are involved in insulin resistance, the cardiometabolic syndrome, and atherosclerosis. Therefore, investigating the relationship between circulating levels of the novel adipocytokines and IGF-1 is worthwhile. The correlation between IGF-1, visfatin, and omentin-1 has not been adequately investigated. In a population-based study, 324 postmenopausal women were randomly selected. Circulating IGF-1, visfatin, omentin-1, adiponectin, and high-sensitivity C-reactive protein (hs-CRP) levels were measured with the highly specific enzyme-linked immunosorbent assay method. In multiple regression analyses adjusted for alkaline phosphatase, osteocalcin, and hs-CRP, circulating IGF-1 was significantly correlated with visfatin levels (standardized β coefficient [β] = 0.13, partial correlation coefficient [r] = 0.12, p = 0.028). The significant positive correlation between serum IGF-1 and visfatin levels remained after additional adjustments for age and BMI (β = 0.12, r = 0.12, p = 0.025), metabolic syndrome (β = 0.13, r = 0.12, p = 0.021), and type 2 diabetes mellitus (β = 0.13, r = 0.12, p = 0.026). No significant correlations were found between IGF-1, adiponectin, and omentin-1. There is a significant correlation between serum IGF-1 and visfatin levels in postmenopausal women beyond metabolic syndrome, type 2 diabetes, bone formation markers, and hs-CRP levels. The observed correlation between higher circulating IGF-1 and the higher visfatin levels might be a physiological compensation and adaptation to protect against visfatin-induced proinflammatory effects. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of olive oil-rich diet on omentin and adiponectin concentrations. This cross-over randomized trial included 17 overweight women. Participants were assigned to consume either a usual (16% saturated fatty acids [SFA] and 8% monounsaturated fatty acid [MUFA]) or an olive oil-rich diet (16% MUFA and 8% SFA) for 6 weeks crossing over after a 2-week washout period. There was no significant difference in the changes of omentin between two dietary interventions. However, in the adjusted model for polyunsaturated fatty acids and fat mass, usual diet tended to decrease omentin levels whilst olive oil-rich diet tended to increase (−56.1 ± 32.0 versus 40.6 ± 32.0 ng/mL;p = .056). Adiponectin levels increased during two periods, but changes were greater during olive oil-rich diet with a trend toward significance (4.8 ± 3.0 versus 13.4 ± 3.0 μg/mL;p = .06). Consumption of olive oil-rich diet tended to increase omentin and adiponectin in comparison with the usual diet. [ABSTRACT FROM PUBLISHER]

The present study was conducted to investigate the effects of marine collagen peptides (MCPs) on glucose metabolism and insulin resistance using a rat model of type 2 diabetes mellitus (T2DM). Forty T2DM obese Wistar rats were randomly assigned to receive varying doses of MCPs or a vehicle control for 4 weeks. Blood glucose and insulin levels, as well as oxidative stress and inflammation were measured. The expression of glucose transporter type 4 (GLUT4) in skeletal muscles and peroxisome proliferator-activated receptor-α (PPAR-α) in livers of T2DM rats was also measured. It was found that in the group of 9.0 g/kg/day MCPs significantly improved glucose, insulin, and homeostatic model assessment-insulin resistance, and increased the insulin sensitivity index (ISI). In addition, the groups of 4.5 and 2.25 g/kg/day MCPs significantly improved liver steatosis. It was also found that MCPs decreased expression of oxidative stress biomarkers and inflammatory cytokines and adipocytokines in T2DM rats. In conclusion, medium and high doses of MCPs (≥4.5 g/kg/day) improved glucose metabolism and insulin sensitivity in T2DM rats. These beneficial effects of MCPs may be mediated by decreasing oxidative stress and inflammation and by up-regulating GLUT4, and PPAR-α activity. [ABSTRACT FROM AUTHOR]

Background: The role of vaspin in the pathogenesis of stable coronary artery disease (SCAD) have been repeatedly addressed in clinical studies. However, from the point of view of clinical practice, the results of earlier studies are still inconclusive.Methods: The data of 106 SCAD patients who received coronary angiography and 85 coronary artery disease-free controls were collected and analysed. The patients were divided into subgroups according to their pre-test probability (PTP) and according to the result of coronary angiography. Fasting vaspin concentrations were compared between subgroups of SCAD patients and between target group and controls. The effect of age and smoking on the result of coronary angiography was compared to the effect of vaspin using the binomial regression.Results: We did not find significant difference in vaspin level between target group and controls. Unless the pre-test probability was taken into account, we did not find vaspin difference in the target group, when dividing patients on the basis of presence/absence of significant coronary stenosis. In the subgroup of SCAD patients with PTP between 15% - 65%, those with significant coronary stenoses had higher mean vaspin concentration (0,579 ± 0,898 ng/ml) than patients without significant stenoses. (0,379 ± 0,732 ng/ml) (t = -2595; p = 0,012; d = 0,658; 1-β = 0,850). Age, smoking status and vaspin significantly contributed to the HSCS prediction in binomial regression model in patients with low PTP (OR: 1.1, 4.9, 8.7, respectively).Conclusion: According to our results, vaspin cannot be used as an independent marker for the presence of CAD in general population. However, our results indicate that measuring vaspin in SCAD patients might be clinically useful in patients with PTP below 66%. [ABSTRACT FROM AUTHOR]

We have demonstrated previously that severe but not moderate vitamin B12 deficiency altered body composition and induced adiposity in female C57BL/6 mice. This study aims to elucidate the effects of chronic transgenerational dietary vitamin B12 restriction on body composition and various biochemical parameters in the F1 generation offspring of our mouse models of severe and moderate vitamin B12 deficiency established earlier. Female weanling C57BL/6 mice received, ad libitum, for 4 weeks a (i) control diet, (ii) vitamin B12-restricted diet with pectin as dietary fiber (severely deficient diet), or (iii) vitamin B12-restricted diet with cellulose as dietary fiber (moderately deficient diet) and then mated with control males. The offspring of control and severely deficient dams continued on the respective diets of their mothers. Few moderately deficient dams were rehabilitated to control diet from parturition and their pups were weaned to control diet. Also, some offspring born to moderately B12 deficient dams were weaned to control diet, while others continued on the same diet as their mothers. Various parameters were determined in the F1 offspring after 12 and 36 weeks of feeding. The results indicate that both severe and moderate maternal vitamin B12 restrictions were associated with accelerated catch-up growth, increased body fat percentage, visceral adiposity, dyslipidemia, fasting hyperglycemia and insulin resistance in the F1 offspring. Inflammation, increased glucocorticoid and oxidative stress and poor antioxidant defence probably underlie these adverse effects. Rehabilitation from parturition but not weaning was beneficial in delaying the onset of the adverse outcomes in the offspring. © 2016 BioFactors, 43(3):400-414, 2017 [ABSTRACT FROM AUTHOR]

Aim Progranulin ( PGRN) is a novel adipocytokine with anti-inflammatory effects in vascular cells. The aim of this study was to clarify the effects of PGRN on reactivity of isolated blood vessel. Methods Isometric contraction of rat isolated superior mesenteric artery was measured. Results Pre-treatment with PGRN (10-100 ng mL−1, 30 min) had no effect on noradrenaline- or 5-hydroxytriptamine-induced contraction. On the other hand, pre-treatment with PGRN (100 ng mL−1) augmented acetylcholine ( ACh; 30 n m)-induced endothelium-dependent relaxation. Pre-treatment with PGRN (100 ng mL−1) augmented ACh (10 μ m)-induced nitric oxide ( NO)-mediated relaxation in the presence of indomethacin (10 μ m), a cyclooxygenase inhibitor, and tetraethyl ammonium (10 m m), a non-selective potassium channel blocker. In contrast, pre-treatment with PGRN (100 ng mL−1) had no effect on ACh-induced endothelium-derived hyperpolarizing factor-mediated relaxation. Pre-treatment with PGRN (100 ng mL−1) had no effect on ACh (10 μ m, 1 min)-induced endothelial NO synthase phosphorylation (at Ser1177) as determined by Western blotting. Pre-treatment with PGRN (100 ng mL−1) augmented an NO donor, sodium nitroprusside ( SNP; 30 n m-1 μ m)- but not a membrane-permeable cGMP analogue, 8-bromo- cGMP-induced relaxation. In the presence of 3-isobutyl-1-methylxanthine (100 μ m), a phosphodiesterase inhibitor, pre-treatment with PGRN (100 ng mL−1) increased SNP (30 n m, 5 min)-induced cGMP production as determined by enzyme immunoassay. Conclusion We for the first time demonstrate that PGRN augments ACh-induced NO-mediated relaxation through the increases of cGMP production in smooth muscle. These results indicate PGRN as a possible pharmacotherapeutic target against cardiovascular diseases including obesity-related hypertension. [ABSTRACT FROM AUTHOR]

Angiotensin II (AngII) is the most important component of angiotensin, which has been regarded as a major contributor to the incidence of hypertension and vascular endothelial dysfunction. The adipocytokine C1q/TNF-related protein 6 (CTRP6) was recently reported to have multiple protective effects on cardiac and cardiovascular function. However, the exact role of CTRP6 in the progression of AngII induced hypertension and vascular endothelial function remains unclear. Here, we showed that serum CTRP6 content was significantly downregulated in SHRs, accompanied by a marked increase in arterial systolic pressure and serum AngII, CRP and ET-1 content. Then, pcDNA3.1-mediated CTRP6 delivery or CTRP6 siRNA was injected into SHRs. CTRP6 overexpression caused a significant decrease in AngII expression and AngII-mediated hypertension and vascular endothelial inflammation. In contrast, CTRP6 knockdown had the opposite effect to CTRP6 overexpression. Moreover, we found that CTRP6 positively regulated the activation of the ERK1/2 signaling pathway and the expression of peroxisome proliferator-activated receptor γ (PPARγ), a recently proven negative regulator of AngII, in the brain and vascular endothelium of SHRs. Finally, CTRP6 was overexpressed in endothelial cells, and caused a significant increase in PPARγ activation and suppression in AngII-mediated vascular endothelial dysfunction and apoptosis. The effect of that could be rescued by the ERK inhibitor PD98059. In contrast, silencing CTRP6 suppressed PPARγ activation and exacerbated AngII-mediated vascular endothelial dysfunction and apoptosis. In conclusion, CTRP6 improves PPARγ activation and alleviates AngII-induced hypertension and vascular endothelial dysfunction. [ABSTRACT FROM AUTHOR]