Serum Of Obese Patients Research Articles

FABP4 in macrophages facilitates obesity-associated pancreatic cancer progression via the NLRP3/IL-1β axis

Obesity is an essential risk factor for pancreatic cancer (PC). Macrophage-induced inflammation plays a pivotal role in obesity-associated carcinogenesis and disease progression; however, the underlying molecular mechanisms remain unclear. In this study, we found that fatty acid-binding protein 4 (FABP4) overexpressed in serum of obese patients and was associated with poor overall survival. In vivo and in vitro experiments have revealed that FABP4 induces macrophage-related inflammation to promote cancer cell migration, invasion and metastasis under obese conditions. Mechanistically, FABP4 participates in transferring saturated fatty acid to induce macrophages pyroptosis in a caspase-1/GSDMD-dependent manner and mediates NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/IL-1β axis in macrophages, which further regulates epithelial-mesenchymal transition signals to promote the migration, invasion, and metastasis of PC cells. Our results suggest that FABP4 in macrophages is a crucial regulator of the NLRP3/IL-1β axis to promote the progression of PC under obese conditions, which could act as a promising molecular target for treating of PC patients with obesity.

Biochemical study of Visfatin Hormone and Some Biochemical Parameters in The Serum of Obese Patients in Nineveh Governorate

Biochemical study of Visfatin Hormone and Some Biochemical Parameters in The Serum of Obese Patients in Nineveh Governorate

ASK1-Interacting Protein 1 Acts as a Novel Predictor of Type 2 Diabetes.

Type 2 diabetes (T2D) mellitus is a chronic inflammatory disease characterized with high secretion of tumor necrosis factor (TNF)-α, but the regulatory pathway of TNF-α production in T2D has not been fully elucidated. ASK1-interacting protein 1 (AIP1) is a signaling scaffold protein that modulates several pathways associated with inflammation. In this study, we aimed to investigate the role of AIP1 in T2D development. Our results revealed that AIP1 was downregulated in omental adipose tissue (OAT) of obese patients with T2D compared with that in obese patients. In addition, Pearson’s correlation test showed that AIP1 was negatively correlated with the homeostatic model assessment for insulin resistance (HOMA-IR, r = -0.4829) and waist-to-hip ratio (r = -0.2614), which are major clinical indexes of T2D. As revealed by the proteomic analysis, immunohistochemistry, and ELISA, the OAT and the serum of obese patients with T2D presented high inflammatory status. And the increased inflammatory factors TNF-α and C-reactive protein C (CRP) in the serum of obese patients with T2D showed a positive correlation with HOMA-IR (TNF-α, r = 0.4728; CRP, r = 0.5522). Interestingly, AIP1 deficiency in adipocytes facilitated TNF-α secretion and retarded glucose uptake. Mechanistically, AIP1 deletion in human adipocytes activated JNK, p38 MAPK, and ERK1/2 signaling. Furthermore, inhibition of these signaling pathways using specific inhibitors could suppress these signal activation and insulin resistance caused by AIP1 deficiency. In addition, AIP1 and TNF-α expression in the OAT of patients with T2D recovered to normal levels after laparoscopic Roux-en-Y gastric bypass (RYGB) surgery. These findings indicate that AIP1 is negatively correlated with the clinical indexes of T2D. It modulates TNF-α expression in OAT via JNK, p38 MAPK, and ERK1/2 signaling.

PPARG expression patterns and correlations in obesity

BackgroundObesity is a result of excess fat storage in tissues and may lead to local insulin resistance and inflammation. Obesity is a multifactorial event and may include dysregulation of certain genes, such as peroxisome proliferator activated receptor gamma (PPARG). PPARG plays a key role in adipogenesis and adipocyte gene expression. AimOur study aimed to determine the regulatory role of PPARG in obesity. MethodsSerum samples from obese, non-obese(controls), diabetic obese and diabetic individuals were collected, and total RNA was extracted. RNA was reversed to cDNA and real time PCR technology was used to quantify differential PPARG gene expression in serum of obese patients and in diabetic obese patients (BMI > 30 kg/m2) versus non-obese and diabetic controls. Anthropometric parameters were recorded, and laboratory measurements were performed for each subject. Demographic and biochemical characteristics were studied for their correlation to PPARG mRNA in each group. The data were analyzed using an ANOVA analysis (p < 0.05). ResultsPPARG mRNA expression is most abundant in serum of obese patients both diabetic and non-diabetic. However, differential level of PPARG mRNA expression was seen in diabetic patients without obesity being only 40% of group subjects showed overexpressed PPARG in serum. A statistically significant differences were observed for mean TGs, TC, LDLc and HDLc levels among groups. There was a strong positive correlation between PPARG mRNA and the body mass index, waist circumference (WC) and waist–hip ratio (WHR) of obese patients.

Biochemical study of apelin hormone and its relationship to insulin and insulin resistance in the serum of obese patients in Nineveh Governorate

The research included (117) cases collected from AL Salam Teaching Hospital in Mosul city, the cases were divided into two group, the first group included (93) patients with obesity either the second group included (24) healthy cases, both groups were divided into three subgroups: (20-35) (36-50) (51 and over) year, and included estimation of Apelin hormone, insulin hormone, insulin resistance, body mass index (BMI), sugar, creatinine, urea, phosphorus and unsaturated iron binding capacity (UIBC) in blood serum of the group of patients with obesity and comparing with control group, the results showed significant increase in alpine, insulin, insulin resistanse, urea, createnine, glogouse but significant decrease in uibc, bmi. The results also showed a positive correlation between Apelin and insulin, urea, creatinine, phosphorus and a negative correlation between Apelin and insulin resistance, glucose, UIBC, BMI.

Serum Level of Inhibin B and Kisspeptin, as well as Their Correlation with Biochemical Factors in Obese Adult Patients.

Obesity is one of the most important global health problems causing serious health risks and early death in human. It is also associated with disturbance of homeostasis of hormones and immunological biochemical factors inside the human body. This study aimed to evaluate the serum level of inhibin B and kisspeptin among Iraqi obese adult people and other biochemical parameters correlated with obesity. Inhibin B and levels of kisspeptin were evaluated in the samples of serum from 40 Iraqi obese adult patients and 30 healthy non-obese individuals. A significant decrease (P<0.0001) was observed in the kisspeptin level in both males and females, compared to the control group. Moreover, inhibin B decreased significantly in obese females only (P<0.001), while there was no differences between males and the control group in this regard. Finally, body mass index, serum glutamic pyruvic transaminase (SGPT), and leptin showed negative correlation with kisspeptin (0.01, 0.5, and 0.01), respectively. However, a positive association was observed with the level of Ca in the serum. On the other hand, inhibin B confirmed a positive correlation with SGPT. The present study revealed a significant increase in inhibin B and kisspeptin, with SGPT and Ca in the serum of obese patients, which could lead to complications and health problems among these patients.

Identification of Differentially Expressed Proteins in Serum of Obese Patients by Isobaric Tags for Relative and Absolute Quantification (iTRAQ)-Coupled 2D LC-MS.

BackgroundThe aim of this study was to identify the differentially expressed proteins of obese patients compared with normal participants and to provide a potential target for future investigation of obesity.Material/MethodsWe enrolled 10 obese male adults and 10 matched normal subjects. Serum samples were collected to get total protein extraction, denaturation, deoxidation, and enzymatic hydrolysis. Differentially expressed proteins were distinguished with mass spectrometry after samples were labeled with iTRAQ.ResultsA total of 9622 differentially expressed peptides were identified, corresponding to 733 proteins; 118 proteins of these showed significant differential expression, with 15 upregulated and 103 downregulated.ConclusionsiTRAQ is an effective technique to identify differentially expressed proteins in obese patients. The development of obesity is correlated with a series of complex elements and mutual effects. The proteins identified in this study may provide novel directions and targets for future pathological studies of obesity.

Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction

Members of the interleukin-1 (IL-1) family are important mediators of obesity and metabolic disease and have been described to often play opposing roles. Here we report that the interleukin-36 (IL-36) subfamily can play a protective role against the development of disease. Elevated IL-36 cytokine expression is found in the serum of obese patients and negatively correlates with blood glucose levels among those presenting with type 2 diabetes. Mice lacking IL-36Ra, an IL-36 family signalling antagonist, develop less diet-induced weight gain, hyperglycemia and insulin resistance. These protective effects correlate with increased abundance of the metabolically protective bacteria Akkermansia muciniphila in the intestinal microbiome. IL-36 cytokines promote its outgrowth as well as increased colonic mucus secretion. These findings identify a protective role for IL-36 cytokines in obesity and metabolic disease, adding to the current understanding of the role the broader IL-1 family plays in regulating disease pathogenesis.

Bariatric Surgery Significantly Reduces Serum Concentration of Vascular Endothelial Growth Factor A and Increases Apelin-12 in Patients with Morbid Obesity

Introduction and Purpose: Obesity is widely known as a major health risk factor, and bariatric surgery has proved to be a sustainable and effective method to reduce body weight. The purpose of this study is to investigate whether bariatric surgery influences concentrations of vascular endothelial growth factor A (VEGF-A) and apelin-12 in the serum of obese patients and whether both hormones correlate with the body mass index (BMI). Materials and Methods: Thirty morbidly obese patients involved in the study underwent sleeve gastrectomy or gastric bypass surgery. Blood samples were obtained preoperatively, 6, 12, and 24 months after surgery. Levels of VEGF-A and apelin-12 in the sera were measured by the use of an enzyme-linked immunosorbent assay. Results and Conclusions: The BMI decreased after the bariatric procedure from 51.3 ± 9.1 to 37.5 ± 7.9 kg/m2 (p < 0.0001). VEGF-A concentration significantly decreased from 189.5 ± 17.2 pg/mL preoperatively to 110.8 ± 19.1 pg/mL after 24 months (p < 0.05). The serum concentration of apelin-12 significantly increased from 482.6 ± 66.6 to 2458.3 ± 499.8 pg/mL 2 years after the surgery (p < 0.0001). VEGF-A is positively correlated with the BMI (r = 0.45, p < 0.0001), whereas apelin-12 has a negative correlation with the BMI (r = −0.28, p < 0.01).

Abstract 17101: Vasoprotective Properties of HDL Improve Early Ater Roux-en-y Gastric Bypass but Not After Diet Treatment: The Superior Cardiometabolic Benefits of RYGB

Introduction: Roux-en-Y gastric bypass (RYGB) reduces cardiometabolic risk through different potential mechanisms. High density lipoprotein cholesterol (HDL-C) changes might explain part of this benefit. Hypothesis: We assessed the effect of RYGB on HDL vasoprotective properties in comparison with a hypocaloric diet-induced weight loss. Methods: HDL was isolated from serum of obese patients (BMI &gt; 35 kg/m2) before and 6 months after RYGB (n=32) or diet (n=32). In endothelial cells stimulated with HDL, we quantified nitric oxide (NO) production by DAF-2 fluorescence and paraoxonase-1 antioxidant activity (PON-1). Total cholesterol, low density lipoprotein (LDL-C), HDL-C, and triglycerides (TG) as well as glucose plasma fasting levels were measured. Results: At baseline there was no significant difference in mean body weight (BW) and BMI between RYGB and diet patients (119.9 Kg; 42kg/m2 vs. 110.9 kg; 37.4 kg/m2, respectively, p=0.06). At 6 months, BW and BMI were not different (RYGB: 94kg; 33 kg/m2; diet: 99kg; 33.4 kg/m2, p=ns). In both groups, mean total cholesterol and TG were reduced; LDL-C decreased only after RYGB. Total HDL-C increased 6 months after both interventions (RYGB: 1.2±0.5 baseline vs 1.3±0.4 after 6months; diet 1.1±0.25 baseline vs 1.3±0.3 after 6months, p&lt;0.05). However, only RYGB improved the vasoprotective HDL-stimulated NO production (RYGB: 234.2±178.0 vs diet 98.8±76.4 arbitrary units, p&lt;0.0001) and HDL-associated PON-1 activity (RYGB: 40% vs diet: 9% increase compared to baseline; p&lt;0.0001). Fasting glucose levels improved in both groups and were not different at 6 months between the two interventions. Conclusions: Our study shows that although HDL concentration increased after RYGB and diet-induced BW loss, only RYGB restored endothelial protective HDL properties even though patients were still obese. This suggests that BW loss is not sufficient or critical to improve the protective properties of HDL, unless accompanied by yet unknown surgery-specific effects.

Modulation of the leptin receptor mediates tumor growth and migration of pancreatic cancer cells.

Obesity has been implicated as a significant risk factor for development of pancreatic cancer. In the setting of obesity, a systemic chronic inflammatory response is characterized by alterations in the production and secretion of a wide variety of growth factors. Leptin is a hormone whose level increases drastically in the serum of obese patients. High fat diet induced obesity in mice leads to an overall increased body weight, pancreatic weight, serum leptin, and pancreatic tissue leptin levels. Here we report the contribution of obesity and leptin to pancreatic cancer growth utilizing an in vivo orthotopic murine pancreatic cancer model, which resulted in increased tumor proliferation with concomitant increased tumor burden in the diet induced obese mice compared to lean mice. Human and murine pancreatic cancer cell lines were found to express the short as well as the long form of the leptin receptor and functionally responded to leptin induced activation through an increased phosphorylation of AKT473. In vitro, leptin stimulation increased cellular migration which was blocked by addition of a PI3K inhibitor. In vivo, depletion of the leptin receptor through shRNA knockdown partially abrogated increased orthotopic tumor growth in obese mice. These findings suggest that leptin contributes to pancreatic tumor growth through activation of the PI3K/AKT pathway, which promotes pancreatic tumor cell migration.

Роль грелина и лептина в регуляции массы тела у пациентов с метаболическим синдромом

The variety of metabolic functions of protein hormones - leptin and ghrelin - determines the difference in the therapeutic approach to the treatment of patients with metabolic syndrome. This paper presents the results of a study of the leptin and ghrelin levels in serum of patients with metabolic syndrome. It was revealed that hyperleptinemia was observed in 20.2% of patients with the most obese women II and III than in men. Leptin resistance is also more common in women than in men by 36.4%. However, the ratio of leptin / BMI against compliance with the recommendations for the treatment of metabolic syndrome in men decreased by 2.1 times faster than that of women. Ghrelin levels remained high in patients with the metabolic syndrome by obesity III and IV degree after ingestion. In these patients the strength of lowering the ghrelin level is proportional to time. The rate of gastric emptying was delayed , and the feeling of satiety did not come. This has contributed to an increase in the amount of food intake and body weight gain at the expense of adipose tissue , producing high levels of leptin. The continued high drop it ghrelin and leptin in serum of obese patients significantly impede range of therapeutic interventions.

Gut Microbial Metabolites of Polyunsaturated Fatty Acids Correlate with Specific Fecal Bacteria and Serum Markers of Metabolic Syndrome in Obese Women

The aim of this human study was to assess the influence of prebiotic-induced gut microbiota modulation on PUFA-derived bacterial metabolites production. Therefore, we analyzed the circulating fatty acid profile including CLA/CLnA in obese women treated during 3months with inulin-type fructan prebiotics. In these patients, we had already determined gut microbiota composition by phylogenetic microarray and qPCR analysis of 16S rDNA. Some PUFA-derived bacterial metabolites were detected in the serum of obese patients. Despite the prebiotic-induced modulation of gut microbiota, including changes in CLA/CLnA-producing bacteria, the treatment did not impact significantly on the circulating level of these metabolites. However, some PUFA-derived bacterial metabolites were positively correlated with specific fecal bacteria (Bifidobacterium spp., Eubacterium ventriosum and Lactobacillus spp.) and inversely correlated with serum cholesterol (total, LDL, HDL). These correlations suggest a potential beneficial effect of some of these metabolites but this remains to be confirmed by further investigation.

Patients affected by metabolic syndrome show decreased levels of circulating platelet derived growth factor (PDGF)-BB

The development and/or progression of metabolic syndrome (MetS) in overweight and obese individuals have been associated to low-grade inflammation, but few studies have simultaneously analyzed the circulating levels of several cytokines. In this pilot study, a group of 27 cytokines and growth factors was analyzed in the serum of obese patients (n=40) diagnosed for MetS in comparison with sex- and age-matched control subjects without MetS (n=53) by using a multiplex immunoassay. Release of cytokines was measured in culture supernatants of human primary endothelial cells, THP-1 macrophagic cells and HuH-7 hepatoma cells upon exposure to a high fat mixture. While the majority of cytokines did not show significant differences between the investigated groups, the circulating levels of CXCL10/IP-10 and IL-6 were higher in the MetS group versus overweight control group. In contrast, PDGF-BB serum levels were significantly decreased in MetS patients. The invitro addition of a high fat mixture increased the release of IL-6 and/or CXCL10/IP-10 in the culture supernatant of human primary endothelial cells and THP-1 macrophagic cells, while the same mixture significantly decreased the release of PDGF-BB by human THP-1 macrophagic and HuH-7 hepatoma cells. The current demonstration that MetS is associated with decrease of the pro-fibrotic PDGF cytokine is a completely novel finding, which adds complexity to the interplay between inflammation and fibrosis in patients affected by MetS.

Effects of Green Tea Supplementation on Elements, Total Antioxidants, Lipids, and Glucose Values in the Serum of Obese Patients

The consumption of green tea has been associated with cardiovascular and metabolic diseases. There have been some studies on the influence of green tea on the mineral status of obese subjects, but they have not yielded conclusive results. The aim of the present study is to examine the effects of green tea extract on the mineral, body mass, lipid profile, glucose, and antioxidant status of obese patients. A randomized, double-blind, placebo-controlled study was conducted. Forty-six obese patients were randomly assigned to receive either 379 mg of green tea extract, or a placebo, daily for 3 months. At baseline, and after 3 months of treatment, the anthropometric parameters, blood pressure, and total antioxidant status were assessed, as were the levels of plasma lipids, glucose, calcium, magnesium, iron, zinc, and copper. We found that 3 months of green tea extract supplementation resulted in decreases in body mass index, waist circumference, and levels of total cholesterol, low-density cholesterol, and triglyceride. Increases in total antioxidant level and in zinc concentration in serum were also observed. Glucose and iron levels were lower in the green tea extract group than in the control, although HDL-cholesterol and magnesium were higher in the green tea extract group than in the placebo group. At baseline, a positive correlation was found between calcium and body mass index, as was a negative correlation between copper and triglycerides. After 3 months, a positive correlation between iron and body mass index and between magnesium and HDL-cholesterol, as well as a negative correlation between magnesium and glucose, were observed. The present findings demonstrate that green tea influences the body's mineral status. Moreover, the results of this study confirm the beneficial effects of green tea extract supplementation on body mass index, lipid profile, and total antioxidant status in patients with obesity.

Chemerin/ChemR23 pathway: a system beyond chemokines

Chemerin is a chemokine that, through the engagement of its counter-receptor, ChemR23, attracts pro-inflammatory cells. However, chemerin has been shown to play other functions and a recent study by Berg and colleagues demonstrates that chemerin/ChemR23 is a system beyond chemokines. Human articular chondrocytes produce chemerin and express ChemR23, and upon stimulation with recombinant chemerin increase the production of pro-catabolic cytokines and metalloproteinases. The latter are up-regulated in osteoarthritic cartilage and cause extracellular matrix breakdown. Since an increase of chemerin in fat tissue and serum of obese patients has been reported, this new feature of chemerin may represent a functional link between obesity and osteoarthritis.

Gender-based dimorphic pattern for interleukin-1 receptor antagonist in type 2 diabetes mellitus

Adipose tissue secretes a variety of cytokines, some of which are increased in the serum of obese patients. The anti-inflammatory interleukin-1 receptor antagonist (IL-1Ra) is the most highly elevated known cytokine in human obesity, and its serum levels are strongly associated with the degree of insulin resistance in non-diabetic patients. Aim The present study examined serum levels of IL-1Ra in type 2 diabetic patients (T2DM) and their relationships with three other adipokines (leptin, interleukin-6 [IL-6], adiponectin). Their correlation with anthropometric and biochemical variables was examined, as well as their intraindividual fluctuations. Methods Fifty T2DM patients, aged 58 ± 13 years, were consecutively recruited among those electively hospitalized for a one-week intensive training course with our Diabetes Education Service. Anthropometric measurements and blood samples were taken after an overnight fast on admission (baseline) and after four days. Results Mean serum levels of IL-1Ra and leptin, but not of IL-6 and adiponectin, were significantly higher in women than in men ( P < 0.0006), and this difference persisted after correction for body mass index (BMI) ( P < 0.0004). In addition, IL-1Ra and leptin were strongly correlated with the BMI ( P < 0.0004). By contrast, no significant correlations were observed between IL-1Ra and glucose-control parameters. Finally, all four adipokines exhibited wide interindividual variability, but with limited intraindividual fluctuations over the short time period. Conclusion IL-1Ra, leptin and adiponectin serum levels exhibit marked interindividual variation with high intraindividual consistency. A gender-based dimorphic pattern for IL-1Ra, independent of the degree of adiposity and glucose control, was also found.

From Fat to Inflammation

From Fat to Inflammation

Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents

The IL-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine known to antagonise the actions of IL-1. We have previously shown that IL-1Ra is markedly upregulated in the serum of obese patients, is correlated with BMI and insulin resistance, and is overexpressed in the white adipose tissue (WAT) of obese humans. The aim of this study was to examine the role of IL-1Ra in the regulation of glucose homeostasis in rodents. We assessed the expression of genes related to IL-1 signalling in the WAT of mice fed a high-fat diet, as well as the effect of Il1rn (the gene for IL-1Ra) deletion and treatment with IL-1Ra on glucose homeostasis in rodents. We show that the expression of Il1rn and the gene encoding the inhibitory type II IL-1 receptor was upregulated in diet-induced obesity. The blood insulin:glucose ratio was significantly lower in Il1rn ( -/- )animals, which is compatible with an increased sensitivity to insulin, reinforced by the fact that the insulin content and pancreatic islet morphology of Il1rn ( -/- ) animals were normal. In contrast, the administration of IL-1Ra to normal rats for 5 days led to a decrease in the whole-body glucose disposal due to a selective decrease in muscle-specific glucose uptake. The expression of genes encoding inhibitors of IL-1 signalling is upregulated in the WAT of mice with diet-induced obesity, and IL-1Ra reduces insulin sensitivity in rats through a muscle-specific decrease in glucose uptake. These results suggest that the markedly increased levels of IL-1Ra in human obesity might contribute to the development of insulin resistance.

Decreased Fat Mass in Interleukin-1 Receptor Antagonist–Deficient Mice

Interleukin (IL)-1 is a regulator of inflammation but is also implicated in the control of energy homeostasis. Because the soluble IL-1 receptor antagonist (IL-1Ra) is markedly increased in the serum of obese patients and is overexpressed in white adipose tissue in obesity, we studied the metabolic consequences of genetic IL-1Ra ablation in mice. We have shown that IL-1Ra-/- mice have a lean phenotype due to decreased fat mass, related to a defect in adipogenesis and increased energy expenditure. The adipocytes were smaller in these animals, and the expression of genes involved in adipogenesis was reduced. Energy expenditure as measured by indirect calorimetry was elevated, and weight loss in response to a 24-h fast was increased in IL-1Ra-/- animals compared with wild-type mice. Lipid oxidation of IL-1Ra-/- mice was higher during the light period, reflecting their reduction in diurnal food intake. Interestingly, IL-1Ra-/- and IL-1Ra+/- mice presented an attenuation in high-fat diet-induced caloric hyperphagia, indicating a better adaptation to hypercaloric alimentation, which is in line with the role of IL-1Ra as a mediator of leptin resistance. Taken together, we show that IL-1Ra is an important regulator of adipogenesis, food intake, and energy expenditure.