Resistin Secretion Research Articles

Inflammation-Involved Proteins in Blood Serum of Cataract Patients-A Preliminary Study.

Approximately 50% of all global blindness is caused by cataract in adults aged ≥50 years. The mechanisms of the disease are most arguably related to a redox imbalance and inflammation; therefore, the aim of the study was to evaluate the processes associated with inflammation in cataract patients. Twenty-four patients aged 22-60 years (62.5% females) participated in the study, with 33 controls aged 28-60 years (66.7% females). Venous blood serum of the subjects was examined for alpha 1-antitrypsin, as well as selected lysosomal enzymes and adipokines. The activities of lysosomal enzymes, as well as the activity of alpha 1-antitrypsin and the concentrations of c-reactive protein and leptin, were similar in the patients versus the controls. The concentrations of interleukin 6 and resistin were lower, in turn, whereas omentin-1 and adiponectin were higher. Moreover, the study revealed the existence of many linear relationships between the parameters, including multiple linear regression, especially gender-wise. No systemic inflammation was probably noted in the cataract patients tested; nevertheless, the deregulation of adiponectin, omentin-1 and resistin secretion was observed.

Myristic Acid Supplementation Aggravates High Fat Diet-Induced Adipose Inflammation and Systemic Insulin Resistance in Mice.

Saturated fatty acids (SFAs) are considered to be detrimental to human health. One of the SFAs, myristic acid (MA), is known to exert a hypercholesterolemic effect in mice as well as humans. However, its effects on altering adipose tissue (AT) inflammation and systemic insulin resistance (IR) in obesity are still unclear. Here, we sought to determine the effects of a high fat (HF) diet supplemented with MA on obesity-associated metabolic disorders in mice. Wild-type C57BL/6 mice were fed a HF diet in the presence or absence of 3% MA for 12 weeks. Plasma lipids, plasma adipokines, AT inflammation, systemic IR, glucose homeostasis, and hepatic steatosis were assessed. The body weight and visceral adipose tissue (VAT) mass were significantly higher in mice receiving the HF+MA diet compared to HF diet-fed controls. Plasma total cholesterol levels were marginally increased in HF+MA-fed mice compared to controls. Fasting blood glucose was comparable between HF and HF+MA-fed mice. Interestingly, the plasma insulin and HOMA-IR index, a measure of insulin resistance, were significantly higher in HF+MA-fed mice compared to HF controls. Macrophage and inflammatory markers were significantly elevated in the AT and AT-derived stromal vascular cells upon MA feeding. Moreover, the level of circulating resistin, an adipokine promoting insulin resistance, was significantly higher in HF+MA-fed mice compared with HF controls. The insulin tolerance test revealed that the IR was higher in mice receiving the MA supplementation compared to HF controls. Moreover, the glucose tolerance test showed impairment in systemic glucose homeostasis in MA-fed mice. Analyses of liver samples showed a trend towards an increase in liver TG upon MA feeding. However, markers of oxidative stress and inflammation were reduced in the liver of mice fed an MA diet compared to controls. Taken together, our data suggest that chronic administration of MA in diet exacerbates obesity-associated insulin resistance and this effect is mediated in part, via increased AT inflammation and increased secretion of resistin.

Gut Microbiota: Target for Modulation of Gut-Liver-Adipose Tissue Axis in Ethanol-Induced Liver Disease.

Consumption of alcohol (ethanol) in various forms has been an integral part of human civilization. Since ages, it also has been an important cause of death and health impairment across the globe. Ethanol-mediated liver injury, known as alcoholic liver disease (ALD), is caused by surplus intake of alcohol. Several studies have proposed the different pathways that may be lead to ALD. One of the factors that may affect the cytochrome P450 (CYP2E1) metabolic pathway is gut dysbiosis. The gut microbiota produces various compounds that play an important role in regulating healthy functions of distal organs such as the adipose tissue and liver. Dysbiosis causes bacteremia, hepatic encephalopathy, and increased intestinal permeability. Recent clinical studies have found better understanding of the gut and liver axis. Another factor that may affect the ALD pathway is dysfunction of adipose tissue metabolism. Moreover, dysfunction of adipose tissue leads to ectopic fat deposition within the liver and disturbs lipid metabolism by increasing lipolysis/decreasing lipogenesis and impaired glucose tolerance of adipose tissue which leads to ectopic fat deposition within the liver. Adipokine secretion of resistin, leptin, and adiponectin is adversely modified upon prolonged alcohol consumption. In the combination of these two factors, a proinflammatory state is developed within the patient leading to the progression of ALD. Thus, the therapeutic approach for treatments and prevention for liver cirrhosis patients must be focused on the gut-liver-adipose tissue network modification with the use of probiotics, synbiotics, and prebiotics. This review is aimed at the effect of ethanol on gut and adipose tissue in both rodent and human alcoholic models.

The Long-Term Effects of High-Fat and High-Protein Diets on the Metabolic and Endocrine Activity of Adipocytes in Rats.

Simple SummaryThe increasing prevalence of worldwide obesity and growing awareness of its negative consequences are forcing scientists to take a new view of nutrition and search for new diets. Therefore, to find some new relationships between diet and metabolism, we analyzed the effects of the long-term (60 and 120 days) use of a high-protein diet (HPD) and of a high-fat diet (HFD) on the metabolic and endocrine functions of fat tissue and on biochemical indices in rat blood in the present study. This research helped us to understand the roles of diet in the metabolic and endocrine functioning of adipocytes. Our study indicated that an HFD has a negative effect on fat tissue function, whereas the HPD showed positive results, such as increased insulin sensitivity and improved glucose and lipid metabolism in isolated adipocytes in vitro.The increasing prevalence of overweight and obesity and the rising awareness of their negative consequences are forcing researchers to take a new view of nutrition and its consequences for the metabolism of whole organisms as well as the metabolism of their individual systems and cells. Despite studies on nutrition having been carried out for a few decades, not many of them have focused on the impacts of these diets on changes in the metabolism and endocrine functions of isolated adipocytes. Therefore, we decided to investigate the effects of the long-term use (60 and 120 days) of a high-fat diet (HFD) and of a high-protein diet (HPD) on basic metabolic processes in fat cells—lipogenesis, lipolysis, and glucose uptake—and endocrine function, which was determined according to the secretion of adipokines into the incubation medium. Our results proved that the HPD diet improved insulin sensitivity, increased the intracellular uptake of glucose (p < 0.01) and its incorporation into lipids (p < 0.01) and modulated the endocrine function of these cells (decreasing leptin secretion; p < 0.01). The levels of biochemical parameters in the serum blood also changed in the HPD-fed rats. The effects of the HFD were inverse, as expected. We observed a decrease in adiponectin secretion and a diminished rate of lipogenesis (p < 0.01). Simultaneously, the secretion of leptin and resistin (p < 0.01) from isolated adipocytes increased. In conclusion, we noted that the long-term use of HPD and HFD diets modulates the metabolism and endocrine functions of isolated rat adipocytes. We summarize that an HFD had a negative effect on fat tissue functioning, whereas an HPD had positive results, such as increased insulin sensitivity and an improved metabolism of glucose and lipids in fat tissue. Moreover, we noticed that negative metabolic changes are reflected more rapidly in isolated cells than in the metabolism of the whole organism.

Fish Oil Enriched in EPA, but Not in DHA, Reverses the Metabolic Syndrome and Adipocyte Dysfunction Induced by a High-Fat Diet

This study aimed to investigate the effects of two commercially available fish oils (FOs) containing different proportions of two omega-3 fatty acids (FA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the metabolic and endocrine dysfunctions of white adipose tissue resulting from obesity. Male C57BL/6J mice, 8 weeks old, received a control or high-fat diet (CO and HF groups, with 9% and 59% energy from fat, respectively) for 8 weeks. The next 8 weeks, the HF group was subdivided into HF, HF+FO/E (HF+5:1 EPA:DHA), and HF+FO/D (HF+5:1 DHA:EPA). Supplementation was performed by gavage, three times a week. All groups that received the HF diet had lower food and caloric intake, but a higher fat intake, body weight (BW) gain, glucose intolerance, and a significant increase in inguinal (ING), retroperitoneal (RP), and epididymal (EPI) adipose tissues when compared to the CO group. Additionally, HF and HF+FO/D groups showed insulin resistance, adipocyte hypertrophy, increased lipolysis and secretion of TNF-α, resistin and IL-10 adipokines by ING and RP adipocytes, and adiponectin only by the HF+FO/D group in ING adipocytes. All of these effects were completely reversed in the HF+FO/E group, which also showed partial reversion in BW gain and glucose intolerance. Both the HF+FO/E and HF+FO/D groups showed a reduction in ING and RP adipose depots when compared to the HF group, but only HF+FO/E in the EPI depot. HF+FO/E, but not HF+FO/D, was able to prevent the changes triggered by obesity in TNF-α, Il-10, and resistin secretion in ING and RP depots. These results strongly suggest that different EPA:DHA ratios have different impacts on the adipose tissue metabolism, FO being rich in EPA, but not in DHA, and effective in reversing the changes induced by obesity.

Adipocytes promote breast tumorigenesis through TAZ-dependent secretion of Resistin

Adipocytes have been implicated in breast tumor growth and stemness maintenance through secreted factors. However, the mechanisms by which these cytokines are regulated during diet-induced obesity and contribute to breast tumorigenesis remain largely unknown. Here we show that transcription cofactor TAZ in adipocytes is directly up-regulated by the free fatty acid/PPARγ axis upon dietary fat stimulation. TAZ knockdown alters the expression profile of a series of secreted proteins and attenuates the tumor-supporting function of adipocytes. Moreover, we identify Resistin, an adipose-derived hormone, as a functional downstream target of TAZ, which facilitates tumorigenesis, and its expression correlated with adipocyitc TAZ in triple-negative breast cancer samples. Further, Adiponectin-cre-mediated TAZ knockout in adipocytes mitigates breast tumor growth. Taken together, our findings highlight how diet-induced TAZ expression in adipocytes promotes tumorigenesis, suggesting promising cancer therapeutic targets.

Resistin is co-secreted with adiponectin in white mouse adipocytes

In the current work we have investigated the cellular and molecular regulation of resistin secretion in cultured and primary mouse adipocytes. Resistin is an adipose tissue hormone proposed to contribute to metabolic disease. In rodents, resistin is secreted from white adipocytes whereas it is in humans synthesised and released from other cell types within white adipose tissue. The metabolic importance of resistin has been studied in both mouse and man, but the regulation of its release remains poorly investigated. Here we define that, in mouse adipocytes, resistin secretion is triggered by an intracellular elevation of cAMP and/or Ca2+. Resistin release is stimulated via activation of beta 3 adrenergic receptors (β3ARs) and the downstream signalling protein exchange protein activated by cAMP (Epac). The secretion of resistin is markedly abrogated in adipocytes isolated from obese and diabetic mice. Immunocytochemical staining demonstrates a significant overlap between signals for resistin and the adipocyte hormone adiponectin. Our data propose that resistin and adiponectin are contained within the same vesicles in mouse adipocytes and that the two hormones are co-secreted in response to the same exocytosis-triggering signals.

Adipocytokines visfatin and resistin in breast cancer: Clinical relevance, biological mechanisms, and therapeutic potential.

Obesity is one of the major modifiable risk factors in breast cancer, with obese adipose tissue showing a pathological role in breast cancer development and malignancy via the release of secretory factors, such as proinflammatory cytokines and adipocytokines. The current article focuses on visfatin and resistin, two such adipocytokines that have emerged over the last two decades as leading breast cancer promoting factors in obesity. The clinical association of circulating visfatin and resistin with breast cancer and their biological mechanisms are reviewed, in addition to their role in the context of tumor-stromal interactions in the breast cancer microenvironment. Recent findings have unraveled several mediators of visfatin and resistin that are involved in the crosstalk between breast cancer cells and adipose tissue in the breast tumor microenvironment, including growth differentiation factor 15 (GDF15), interleukin 6 (IL-6), and toll-like receptor 4 (TLR4). Finally, current therapeutics targeting visfatin and resistin and their respective pathways are discussed, including future therapeutic strategies such as new drug design or neutralizing peptides that target extracellular visfatin or resistin. These hold promise in the development of novel breast cancer therapies and are of increasing relevance as the prevalence of obesity-related breast cancer increases worldwide.

Fetal circulating human resistin increases in diabetes during pregnancy and impairs placental mitochondrial biogenesis

BackgroundDiabetes during pregnancy affects placental mitochondrial content and function, which has the potential to impact fetal development and the long-term health of offspring. Resistin is a peptide hormone originally discovered in mice as an adipocyte-derived factor that induced insulin resistance. In humans, resistin is primarily secreted by monocytes or macrophages. The regulation and roles of human resistin in diabetes during pregnancy remain unclear.MethodsFetal resistin levels were measured in cord blood from pregnancies with (n = 42) and without maternal diabetes (n = 81). Secretion of resistin from cord blood mononuclear cells (CBMCs) was measured. The actions of human resistin in mitochondrial biogenesis were determined in placental trophoblastic cells (BeWo cells) or human placental explant.ResultsConcentrations of human resistin in cord sera were higher in diabetic pregnancies (67 ng/ml) compared to healthy controls (50 ng/ml, P < 0.05), and correlated (r = 0.4, P = 0.002) with a measure of maternal glycemia (glucose concentration 2 h post challenge). Resistin mRNA was most abundant in cord blood mononuclear cells (CBMCs) compared with placenta and mesenchymal stem cells (MSCs). Secretion of resistin from cultured CBMCs was increased in response to high glucose (25 mM). Exposing BeWo cells or human placental explant to resistin decreased expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), mitochondrial abundance, and ATP production.ConclusionsResistin is increased in fetal circulation of infants exposed to the diabetic milieu, potentially reflecting a response of monocytes/macrophages to hyperglycemia and metabolic stresses associated with diabetes during pregnancy. Increased exposure to resistin may contribute to mitochondrial dysfunction and aberrant energy metabolism characteristic of offspring exposed to diabetes in utero.

Testosterone deficiency and non-alcoholic fatty liver disease in men with type 2 diabetes mellitus

BACKGROUND: Current studies investigated diseases associated with testosterone (T) deficiency; however, data on the combination of non-alcoholic fatty liver disease (NAFLD) with hypogonadism and diabetes mellitus (DM) in men are extremely limited.&#x0D; AIMS: To evaluate the effects of hypogonadism on the formation and progression of NAFLD in men with type 2 DM.&#x0D; METHODS: The study included 90 men with type 2 DM [age 54 (4957) years]. Patients underwent clinical examinations, biochemical analysis (alanine aminotransferase (ALT), aspartate aminotransferase, gamma-glutamyl transpeptidase (GGTP), fasting glucose, immunoreactive insulin, HOMA index, HbA1c, lipid profile), immune enzyme analysis (luteinising hormone, total T, sex hormone binding globulin, resistin, adiponectin, leptin) and magnetic resonance imaging with liver fat fraction determination were performed. Patients were divided into two groups: 132 eugonadal patients and 258 men with newly diagnosed hypogonadism.&#x0D; RESULTS: Increased insulin resistance, hyperinsulinemia, hypertriglyceridemia were observed in men with hypogonadism compared to eugonadal patients. Along with biochemical signs of impaired liver function, such as an increase in liver enzyme concentrations of ALT by 24.5% (p = 0.02), GGTP by 60.5% (p = 0.001), de Rytis coefficient by 60.4% (p = 0.047), of men in the 2nd group, the liver fat fraction also increased, which together indicates NAFLD progression. The proton density of the liver fat fraction according to MRI was 4.12 [2.255.30] % in the 1st group and 10.30 [7.78; 14.44] % in the 2nd group (p=0.001). This was accompanied by an increase in fat production of resistin by 2 times and leptin by 12 times (p 0.001) in patients of group 2 compared to 1.&#x0D; CONCLUSIONS: The combination of type 2 DM with hypogonadism in men leads not only to deterioration of carbohydrate and lipid metabolism but also to disturbance of liver function: increased ALT, GGTP concentrations and liver fat. Increased secretion of leptin and resistin in the adipose tissue is assumed to be a pathogenetically associated with the development of carbohydrate and lipid metabolism disorders, NAFLD and T deficiency.

Lmo4-resistin signaling contributes to adipose tissue-liver crosstalk upon weight cycling.

Repeated cycles of weight loss and regain, known as weight cycling, is often seen when people try to lose weight. The exact pathophysiological effects and the underlying mechanisms of weight cycling remain largely unclear. Here, we report that weight cycling induced by alternating feeding mice with a low-fat diet or a high-fat diet in a 1-week switch protocol caused further increased epididymal white adipose tissue (eWAT) weight, preadipocyte proliferation, hepatic inflammation, fasting blood glucose level, and glucose intolerance, compared with the continuously HF-fed mice. Combining the secretory protein database with RNA-sequencing and quantitative PCR (qPCR) results in eWAT, the mRNA levels of several adipokines, including Retn (encoding resistin), were found altered by weight cycling. A transcriptional co-factor Lmo4 was found regulated by weight cycling; Lmo4 enhanced preadipocyte proliferation, in vitro adipogenesis, transcription of Retn, and resistin secretion in 3T3-L1 cells. Primary mouse hepatocytes administrated with recombinant mouse resistin (rm-resistin), or exposed to media from Lmo4-overexpressed 3T3-L1 cells, showed increased inflammatory responses and gluconeogenesis. Furthermore, rm-resistin-injected normal chow-fed mice showed upregulated blood glucose level by increasing gluconeogenesis, and upregulated the hepatic inflammatory responses. Together, our results suggest a regulatory role of Lmo4-resistin signaling in weight cycling, indicating a crosstalk between the adipose tissue and liver.

Trelagliptin succinate: DPP-4 inhibitor to improve insulin resistance in adipocytes

Trelagliptin inhibits the enzyme dipeptidyl-4 (DPP-4) to treat type 2 diabetes and it may possess the potential to improve insulin resistance. However, the molecular mechanism is not known. In this study, the effect of trelagliptin succinate in improving insulin resistance was investigated. The differentiation system of 3T3-L1 mouse preadipocytes was used to determine the content of adipokines and the content of GLUT4 in the outer membrane. The expression of AKT, P-AKT, IRS-1 and P-IRS-1 in differentiated 3T3-L1 adipocytes was determined by western blotting. Our results demonstrated that trelagliptin succinate increased the expression of AKT, P-AKT, IRS-1 and P-IRS-1 in the PI-3K/AKT insulin signaling pathway. These events promote the trans-membrane function of GLUT4 and concomitant glucose intake in adipocytes. In addition, the secretion of free fatty acids and resistin were decreased. In conclusion, our study suggested that trelagliptin succinate improved insulin resistance in adipocytes via regulation of PI-3K/AKT/GLUT4 insulin signaling pathway.

Assessment of selected adipocytokines in obese women with postmenopausal osteoporosis.

Osteoporosis and obesity are considered civilisation diseases. Menopause is a time of increased bone resorption and increased mass of adipose tissue. Adipocytokines secreted by the adipose tissue are believed to be a potential factor in the pathogenesis of osteoporosis. The aim of this research was to assess leptin, adiponectin, and resistin secretion in obese postmenopausal women with osteoporosis and determine whether obesity might be a factor mitigating the risk of osteoporosis. The study involved 80 postmenopausal women with osteoporosis divided into groups: I with BMI of 30.0 34.9, obese; and II with BMI of 18-24.9, normoweight. Leptin, adiponectin and resistin concentrations were assessed, and bone mineral density (BMD) was measured in the L1-L4 section of the spine using the DXA densitometric method. The results of the comparison of the two groups indicate a statistically significant dependence in groups regarding leptin secretion; the group of obese women demonstrated significantly higher concentrations. No differences between the groups were demonstrated for adiponectin or resistin secretion. Higher leptin concentration and a positive correlation with BMI was confirmed in obese postmenopausal women with osteoporosis. It was also demonstrated that BMD increases with growing BMI. No effect of obesity on the secretion of adiponectin or resistin in women with postmenopausal osteoporosis was found. From among the investigated adipocytokines, only leptin can be considered a bone tissue protective factor in postmenopausal women.

2-OHOA supplementation reduced adiposity and improved cardiometabolic risk to a greater extent than n-3 PUFA in obese mice

ObjectiveWe aimed to assess whether 2-hydroxyoleic acid (2-OHOA) and n-3 polyunsaturated fatty acids (PUFA) could counteract changes on adipokine secretion and cardiometabolic risk biomarkers associated with high-fat diet-induced obesity in mice. MethodsFemale ICR/CD1 mice (8 weeks old) were divided into four groups receiving different diets (n=8/group): (1) standard chow (control) for 18 weeks; (2) 22% fat for 4 weeks + 60% fat for 14 weeks (obesogenic diet, OD); 3) OD + 2-OHOA (1500mgkg−1 diet) for the last 6 weeks (ODHO); and 4) OD+n-3 PUFA (eicosapentaenoic+docosahexaenoic acids, 1500+1500mgkg−1 diet) for the last 6 weeks (OD-N3). After 18 weeks, body weight, periovarian visceral fat, heart and liver weights were measured, as well as cardiometabolic parameters (systolic and diastolic blood pressure, blood glucose, insulin, HOMA index, triglycerides, total cholesterol, apolipoproteins A1 and E), plasma adipokines and inflammatory proteins (leptin, adiponectin, plasminogen activator inhibitor 1 [PAI1], soluble E-selectin [sE-selectin], matrix metalloproteinase-9 [MMP-9], fibrinogen, soluble intercellular adhesion molecule [sICAM] and soluble vascular adhesion molecule [sVCAM]), and secretion of pro-inflamatory cytokines and inflammatory biomarkers from periovarian adipocytes. ResultsOD mice had greater body and heart weights, and plasma leptin, and lower adiponectin and resistin secretion from adipocytes. Supplementation with 2-OHOA reduced body and heart weights, blood pressure, triglycerides and leptin, and restored adiponectin and resistin secretion, while n-3 PUFA only reduced triglyceride levels (all P<0.05). Conclusion2-OHOA supplementation was more effective in reducing adiposity, modulating adipokine secretion and ameliorating cardiometabolic risk than n-3 PUFA.

Association among resistin, adenylate cyclase-associated protein 1 and high-density lipoprotein cholesterol in patients with colorectal cancer: a multi-marker approach, as a hallmark of innovative predictive, preventive, and personalized medicine

Elevated concentrations of resistin have been reported in colorectal cancer (CRC), but its interactions with adenylate cyclase-associated protein 1 (CAP-1) are largely unexplored. We investigated resistin plasma concentration, peripheral blood mononuclear cells (PBMCs) resistin messenger ribonucleic acid (mRNA), and CAP-1 mRNA levels in CRC patients, as well as the impact of resistin gene polymorphism rs1862513 on the examined markers. We also explored associations of resistin with high-density lipoprotein cholesterol (HDL-C) and predictive potential of our parameters for CRC. Eighty-six patients with CRC and 75 healthy adults were included. Commercial ELISA kit was used for obtaining resistin's concentrations, while polymerase chain reaction (PCR) method was applied for evaluation of resistin and CAP-1 mRNA levels and rs1862513 polymorphism. Plasma resistin and CAP-1 mRNA levels were higher in CRC patients (p < 0.001 and p < 0.05, respectively), while resistin mRNA levels were lower (p < 0.001). Negative association existed among plasma resistin and HDL-C concentrations (ρ = - 0.280; p < 0.05). A model including age, body-mass index, HDL-C, low-density lipoprotein cholesterol (LDL-C), and plasma resistin concentrations as independent predictors of CRC showed very good diagnostic accuracy (AUC = 0.898). We found no associations of rs1862513 with the examined markers. Our study demonstrated increased plasma resistin and CAP-1 mRNA levels, implying their possible interaction in CRC. The association among plasma resistin and HDL-C might indicate that HDL-C is involved in alterations of resistin's secretion process. As a hallmark of personalized medicine, multi-marker approach in determination of resistin-related parameters might be useful for prediction and prevention of CRC development.

The effects of eight weeks anaerobic interval training on serum levels of resistin and vaspin and insulin resistance in obese men with type-2 diabetes

Background: Increased secretion of Resistin impaired the insulin function and glucose metabolism, and also Vaspin had an impact on insulin resistance and can play an anti-inflammatory role. This study aimed to investigate the effects of eight weeks anaerobic interval training on serum levels of Resistin and Vaspin and Insulin Resistance. Methods: This quasi-experimental study included obese men with type-2 diabetes that 28 people of them were selected and divided into two group Control and Experimental (n=14). The experimental group performed anaerobic interval exercises for 8 weeks, 3 sessions per week. The blood samples were collected from all the subjects before and after 8 weeks. The assumptions of homogeneity of the slope of the regression line and also the linearity of the relationship between the scores before and after the practice is used and after the confirmation, Covariance analysis test is used (The significance level was considered p≤0/05). Results: The anaerobic interval training has significantly reduce Vaspin (p= <0.0001, f=43.243), Resistin (p=<0.0001, f=40.957) and Insulin Resistance (p=< 0.001, f= 52.024). Conclusion: The anaerobic interval training by weight loss and body fat percentage reduction, leading to significant reduction in serum Resistin and Vaspin and also Insulin resistance, therefore it can be used as a complementary therapy for obese patients and patients with type-2 diabetes.

Evidence of an anti-inflammatory toll-like receptor 9 (TLR 9) pathway in adipocytes.

Adipocytes express various pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and actively participate in anti-bacterial and anti-viral host defence. Obesity is associated with adipose tissue PRR expression. The potential role of Toll-like receptor 9 (TLR9) in adipocytes has not yet been investigated. Here, we evaluated TLR9 expression during adipocyte differentiation (AD) of 3T3-L1 adipocytes, in primary murine adipocytes and in different murine and human adipose tissue depots by real-time PCR, immunocytochemistry and immunohistochemistry. TLR9 expression was inhibited using specific siRNA-mediated knockdown, and TLR9 signaling was induced using specific class A, B and C agonistic CpG-oligodeoxynucleotide (ODN) treatment vs ODN controls in 3T3-L1 adipocytes and in primary murine adipocytes from Tlr9wt/wt vs Tlr9-/- mice. We found that TLR9 gene expression is induced during AD and that TLR9 protein is expressed in murine gonadal and human visceral adipocytes. AD depends on intact TLR9 expression. Tlr9-/- mice demonstrate significantly reduced adiponectin serum levels, while siRNA-mediated TLR9 knockdown led to reduced adiponectin mRNA expression in adipocytes. TLR9 ligands (CpG-ODNs) inhibit pro-inflammatory resistin secretion in mature 3T3-L1 adipocytes. Tlr9-/- as compared to Tlr9wt/wt adipocytes exhibit increased resistin and MCP1 secretion and reduced adiponectin secretion into cell culture supernatants, while TLR9 ligands (ODNs) show differential effects in Tlr9-/- vs Tlr9wt/wt primary murine adipocytes. TLR9 expression is significantly increased in visceral compared to subcutaneous adipose tissue depots in non-diabetic obese patients and correlates with systemic resistin levels in a compartment-specific manner. Thus, adipocytic TLR9 is a putative, new protective factor during (obesity-associated) adipose tissue inflammation.

Soyasapogenols reduce cellular triglyceride levels in 3T3-L1 mouse adipocyte cells by accelerating triglyceride lipolysis

Soyasapogenol is a soyasaponin aglycone, which has been suggested to exert a more potent function than the glycoside form. In this study, the effect of soyasapogenol A and B on cultured adipocyte cell function was investigated using mouse 3T3-L1 adipocyte cells. 3T3-L1 cells were treated with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine for differentiation to adipocytes, and the cells were then cultured in the presence of soyasapogenol A or B (6.25 or 12.5 µM). The media were harvested and refreshed every 2 d. After a 10 d culture, the cells were harvested and the triglyceride content of the cells was determined. The triglyceride content of soyasapogenol B-treated cells was significantly lower than those of vehicle-treated cells. Glycerol and free fatty acid levels in the soyasapogenol-treated cell media were higher than those in vehicle cells. However, there was no difference in the level of adipose triglyceride lipase among soyasapogenol A-, soyasapogenol B-, and vehicle-treated cells. The secreted adiponectin and resistin levels of soyasapogenol-treated cell media were also different compared with those of vehicle-treated cells. Especially, the secreted resistin level in soyasapogenol B-treated cell media was obviously reduced compared with that of vehicle-treated cells. Taken together, these results suggest that soyasapogenol B exerted an anti-obesity and anti-diabetic effect on adipocytes by lowering the cellular triglyceride level by accelerating triglyceride lipolysis with reduced resistin secretion.

The Role of Single Nucleotide Polymorphisms in the GIPR Gene in Regulation of Secretion of Hormones and Adipokines in Obese Patients with Type 2 Diabetes Mellitus

The relationship between the rs2302382, rs8111428 and Glu354Gln (rs1800437) polymorphisms in the GIPR (glucose-dependent insulinotropic polypeptide receptor) gene and plasma levels of mediators involved in the regulation of carbohydrate metabolism has been investigated in obese patients with type 2 diabetes mellitus (T2DM) before and after test breakfast. The contribution of the polymorphic variants of rs2302382, rs8111428 in the GIPR gene contributed to T2DM genetic predisposition in Russian individuals belonging to the Slavic population. Polymorphisms rs2302382 and rs8111428 in the GIPR gene were characterized by the linkage disequilibrium. The decrease in the expression level of the GIPR gene in mesenteric adipose tissue of the small intestine in the carriers of the CC genotype rs2302382 and AA rs8111428 was associated with the increase in the plasma leptin level, whereas during its normal expression, the plasma content of insulin, and GIP (in persons with the CA genotype of the polymorphism rs2302382 and AG polymorphism rs8111428), resistin and ghrelin (in individuals with the CA genotype of the polymorphism rs2302382) increased. We propose the stimulating effect of GIP on the secretion of resistin, leptin and ghrelin, with an increase in insulin production in obese patients with T2DM.

Regulation and Role of Human Resistin in Diabetes during Pregnancy

Diabetes during pregnancy affects placental function, which impacts fetal development and the long-term health of offspring. Resistin is a peptide hormone originally discovered in mice as an adipocyte-derived factor that induced insulin resistance. Unlike rodent, human resistin is primarily secreted by monocytes or macrophages. Resistin may act differently in humans, which remains unclear. The present study examined the effects of maternal diabetes on fetal resistin levels and the actions of human resistin in placenta mitochondrial biogenesis pathway. Concentrations of human resistin in cord sera were higher in diabetic pregnancies (67 ng/ml, n=42) compared to healthy controls (50 ng/ml, n=81, P&amp;lt; 0.05), and correlated (r=0.4, P=0.002) with a measure of maternal glycemia (glucose concentration 2 h post challenge). Resistin mRNA was abundant in cord blood mononuclear cells (CBMCs). Secretion of resistin from cultured CBMCs was increased in response to high glucose (25 mM) treatment. Exposing placental trophoblastic cells (BeWo cells) or human placental explant to resistin decreased expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), as well as the abundance of mitochondria transcription factor A (TFAM). In human term placentae, the levels of PGC-1α promotor methylation were positively correlated with cord blood resistin concentrations (r= 0.45, p=0.04, n=16). In summary, we have shown that resistin is increased in the fetal circulation during diabetic pregnancy and that this potentially reflects the response of monocytes/macrophages to hyperglycemia and metabolic stresses associated with diabetic pregnancy. In addition, human resistin has the capacity to decrease mitochondrial biogenesis by affecting the epigenetic regulation of PGC-1α expression. Thus, increased exposure to resistin may contribute to mitochondrial dysfunction and long-term aberrant energy metabolism characteristic of the offspring of diabetic pregnancies. Disclosure S. Jiang: None. A.M. Teague: None. J.B. Tryggestad: None. T. Lyons: None. S. Chernausek: Advisory Panel; Self; Novo Nordisk Inc..