scholarly journals Adipose Tissue Steroid Receptor RNA Activator 1 (SRA1) Expression Is Associated with Obesity, Insulin Resistance, and Inflammation

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2602
Author(s):  
Shihab Kochumon ◽  
Hossein Arefanian ◽  
Sardar Sindhu ◽  
Steve Shenouda ◽  
Reeby Thomas ◽  
...  

Steroid receptor RNA activator 1 (SRA1) is involved in pathophysiological responses of adipose tissue (AT) in obesity. In vitro and animal studies have elucidated its role in meta-inflammation. Since SRA1 AT expression in obesity/type 2 diabetes (T2D) and the relationship with immune-metabolic signatures remains unclear, we assessed AT SRA1 expression and its association with immune–metabolic markers in individuals with obesity/T2D. For this, 55 non-diabetic and 53 T2D individuals classified as normal weight (NW; lean), overweight, and obese were recruited and fasting blood and subcutaneous fat biopsy samples were collected. Plasma metabolic markers were assessed using commercial kits and AT expression of SRA1 and selected immune markers using RT-qPCR. SRA1 expression was significantly higher in non-diabetic obese compared with NW individuals. SRA1 expression associated with BMI, PBF, serum insulin, and HOMA-IR in the total study population and people without diabetes. SRA1 associated with waist circumference in people without diabetes and NW participants, whereas it associated inversely with HbA1c in overweight participants. In most study subgroups AT SRA1 expression associated directly with CXCL9, CXCL10, CXCL11, TNF-α, TGF-β, IL2RA, and IL18, but inversely with CCL19 and CCR2. TGF-β/IL18 independently predicted the SRA1 expression in people without diabetes and in the total study population, while TNF-α/IL-2RA predicted SRA1 only in people with diabetes. TNF-α also predicted SRA1 in both NW and obese people regardless of the diabetes status. In conclusion, AT SRA1 expression is elevated in people with obesity which associates with typical immunometabolic markers of obesity/T2D, implying that SRA1 may have potential as a biomarker of metabolic derangements.

2016 ◽  
Author(s):  
Luciana L A Ventura ◽  
Nathália C L Fortes ◽  
Helton C Santiago ◽  
Marcelo Vidigal Caliari ◽  
Maria A Gomes ◽  
...  

Background. Currently, the number of obese people in the world has reached alarming proportions. During the expansion of adipose tissue, a number of functions such as activation and release of cytokines and hormones may be affected. This causes the body to take a pro-inflammatory pattern, which may affect the proper functioning of many tissues. Thus, studying the mechanisms by which obesity induces physiological disorders is necessary, and may be facilitated by the use of animal models, in particular rodents. We sought to investigate whether the gerbil (Meriones unguiculatus) would be a good experimental model for the study of obesity and metabolic changes resulting from a diet rich in fats and sugars. Methods. 14 gerbils were divided according to weight into two experimental groups and received a a standard diet with 4,15kcal/g (CT; n = 7) or a diet rich in simple carbohydrates and fats with 5,86kcal/g (OB, n = 7) for 11 weeks. The animals had free access to water and food. The weight of each animal and food consumption of each cage were measured weekly and at the end of the experiment, blood, adipose tissue and liver were collected. The following parameters were determined: cholesterol (COL), triglycerides (TGL) and glycemia (GLI) in the plasma; cytokines (IL-6, IL-10 and TNF-α) and hormones (adiponectin and leptin) in adipose tissue; activity of superoxide dismutase (SOD) and catalase (CAT), extraction and differentiation of fat in the liver and liver histology. Results. The consumption of a diet rich in simple fats and carbohydrates led to an increase of total body weight, relative weights of liver and adipose tissue, glucose and triglycerides levels, and TNF-α concentration in adipose tissue. Animals of this group also showed a significant increase of total fat, cholesterol and triglyceride content in the liver, contributing to higher intensity of hepatic steatosis. On the other hand, depletion in the enzyme activity of SOD and CAT in the liver, as well as reduction of IL-10 and adiponectin levels were found in adipose tissue of these animals. Conclusion. Diet consumption consisting of an excess in saturated fat and simple carbohydrates establish the gerbil as an experimental model for the study of obesity and metabolic and liver abnormalities resulting from this disease.


2007 ◽  
Vol 292 (3) ◽  
pp. E740-E747 ◽  
Author(s):  
S. J. Creely ◽  
P. G. McTernan ◽  
C. M. Kusminski ◽  
ff. M. Fisher ◽  
N. F. Da Silva ◽  
...  

Type 2 diabetes (T2DM) is associated with chronic low-grade inflammation. Adipose tissue (AT) may represent an important site of inflammation. 3T3-L1 studies have demonstrated that lipopolysaccharide (LPS) activates toll-like receptors (TLRs) to cause inflammation. For this study, we 1) examined activation of TLRs and adipocytokines by LPS in human abdominal subcutaneous (AbdSc) adipocytes, 2) examined blockade of NF-κB in human AbdSc adipocytes, 3) examined the innate immune pathway in AbdSc AT from lean, obese, and T2DM subjects, and 4) examined the association of circulating LPS in T2DM subjects. The findings showed that LPS increased TLR-2 protein expression twofold ( P < 0.05). Treatment of AbdSc adipocytes with LPS caused a significant increase in TNF-α and IL-6 secretion (IL-6, Control: 2.7 ± 0.5 vs. LPS: 4.8 ± 0.3 ng/ml; P < 0.001; TNF-α, Control: 1.0 ± 0.83 vs. LPS: 32.8 ± 6.23 pg/ml; P < 0.001). NF-κB inhibitor reduced IL-6 in AbdSc adipocytes (Control: 2.7 ± 0.5 vs. NF-κB inhibitor: 2.1 ± 0.4 ng/ml; P < 0.001). AbdSc AT protein expression for TLR-2, MyD88, TRAF6, and NF-κB was increased in T2DM patients ( P < 0.05), and TLR-2, TRAF-6, and NF-κB were increased in LPS-treated adipocytes ( P < 0.05). Circulating LPS was 76% higher in T2DM subjects compared with matched controls. LPS correlated with insulin in controls ( r = 0.678, P < 0.0001). Rosiglitazone (RSG) significantly reduced both fasting serum insulin levels (reduced by 51%, P = 0.0395) and serum LPS (reduced by 35%, P = 0.0139) in a subgroup of previously untreated T2DM patients. In summary, our results suggest that T2DM is associated with increased endotoxemia, with AT able to initiate an innate immune response. Thus, increased adiposity may increase proinflammatory cytokines and therefore contribute to the pathogenic risk of T2DM.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2967 ◽  
Author(s):  
Luciana L.A. Ventura ◽  
Nathália C.L. Fortes ◽  
Helton C. Santiago ◽  
Marcelo V. Caliari ◽  
Maria A. Gomes ◽  
...  

Background Nowadays, the number of obese people in the world has reached alarming proportions. During the expansion of adipose tissue, a number of functions such as activation and release of cytokines and hormones may be affected. This leads the body to a pro-inflammatory pattern, which may affect the proper functioning of many tissues. Thus, studying the mechanisms by which obesity induces physiological disorders is necessary, and may be facilitated by the use of animal models, in particular rodents. We sought to characterize the metabolic and adipose tissue changes resulting from a diet rich in fats and simple sugars in gerbils. Methods We divided 14 gerbils into two experimental groups that received a diet rich in simple carbohydrates and fats with 5,86 kcal/g (OB, n = 7) or a standard diet with 4.15 kcal/g (CT; n = 7) for 11 weeks. The animals had free access to water and food. The animal weight and food consumption were measured weekly. Blood, adipose tissue and liver of each animal were collected at the end of experiment. The following parameters were determined: cholesterol (COL), triglycerides (TGL) and glycemia (GLI) in the plasma; cytokines (IL-6, IL-10 and TNF-α) and hormones (adiponectin and leptin) in adipose tissue; activity of superoxide dismutase (SOD) and catalase (CAT), extraction and differentiation of fat and histology in liver. Results The consumption of a diet rich in simple carbohydrates and fats led to increased total body weight and increased relative weights of liver and adipose tissue. In addition, we observed increased fasting glucose levels and circulating triglycerides, along with high TNF-α production in adipose tissue and increased total fat, cholesterol and triglyceride contents in the liver, contributing to higher intensity of hepatic steatosis. On the other hand, the animals of this group showed depletion in the enzyme activity of SOD and CAT in the liver, as well as reduction of IL-10 and adiponectin levels in adipose tissue. Discussion High intake of saturated fat and simple carbohydrates establish the gerbil as an experimental model for the study of metabolic and hepatic abnormalities resulting from obesity.


2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Akadiri Yessoufou ◽  
Kabirou Moutairou ◽  
Naim Akhtar Khan

Objective. This study is conducted on a model of insulin-resistant (IR) mice born to dams which were rendered diabetic by the administration of streptozotocin.Methods. Adult IR and control offspring were selected and we determined the mRNA expression of transcription factors known to modulate pancreatic and adipose tissue activities and inflammation.Results. We observed that serum insulin increased, and the mRNA of insulin gene transcription factors, Pdx-1, Nkx6.1 and Maf-A, were upregulated in IR mice pancreas. Besides, their pancreatic functional capacity seemed to be exhausted as evidenced by low expression of pancreatic Glut2 and glucokinase mRNA. Though IR offspring exhibited reduced epididymal adipose tissue, their adipocytes seemed to be differentiated into macrophage-like cells, as they exhibited upregulated CD14 and CD68 antigens, generally expressed by macrophages. However, there was no peripheral macrophages infiltration into epididymal adipose tissue, as the expression of F4/80, a true macrophage marker, was undetectable. Furthermore, the expression of IL-6, TNF-α and TLR-2, key players of insulin resistance, was upregulated in the adipose tissue of IR offspring.Conclusion. Insulin resistant state in mice, born to diabetic pregnancy, alters the expression of function-related genes in pancreas and epididymal adipose tissue and these offspring are prone to develop metabolic syndrome.


Perfusion ◽  
2016 ◽  
Vol 32 (4) ◽  
pp. 279-284 ◽  
Author(s):  
Lukas Mach ◽  
Helena Bedanova ◽  
Miroslav Soucek ◽  
Michal Karpisek ◽  
Tomas Konecny ◽  
...  

Background: Cardiac surgery and cardiopulmonary bypass (CPB) have been shown to stimulate a systemic inflammatory response which has been associated with adverse postoperative outcomes. Adipose tissue, both epicardial (EAT) and subcutaneous (SAT), is a known source of inflammatory cytokines, but its role in the pathophysiology of surgery- and CPB-induced systemic inflammatory response has not been fully elucidated. Therefore, we conducted a study to establish levels of selected cytokines in EAT and SAT prior to and after surgery with CPB. Methods: Adipose tissue samples were obtained from patients undergoing planned cardiac surgery on CPB. Samples from EAT and SAT were collected before and immediately after CPB. Levels of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), adipocyte fatty acid-binding protein (AFABP), leptin and adiponectin were determined by ELISA, which were adjusted for a total concentration of proteins in the individual samples. Results: Samples from 77 patients (mean age 67.68 ± 11.5 years) were obtained and analysed. Leptin, adiponectin, TNF-α and AFABP were shown to decrease their concentrations statistically significantly in the EAT after CPB while no statistically significant drop was observed in the SAT. On the contrary, IL-6 showed only a slight and statistically insignificant decrease in the EAT after CPB and it was in the SAT where a statistically significant drop was observed. Discussion: One of the most relevant findings of this study was the marked decrease in EAT levels of TNF-α, AFABP, leptin and adiponectin after the CPB termination. Our results suggest that EAT might serve as a pool of cytokines which are released into the circulation in reaction to surgery with CPB. Should these novel findings be confirmed, new strategies to assess and possibly reduce EAT contribution on adverse outcomes of cardiac surgery may be developed.


2016 ◽  
Author(s):  
Luciana L A Ventura ◽  
Nathália C L Fortes ◽  
Helton C Santiago ◽  
Marcelo Vidigal Caliari ◽  
Maria A Gomes ◽  
...  

Background. Currently, the number of obese people in the world has reached alarming proportions. During the expansion of adipose tissue, a number of functions such as activation and release of cytokines and hormones may be affected. This causes the body to take a pro-inflammatory pattern, which may affect the proper functioning of many tissues. Thus, studying the mechanisms by which obesity induces physiological disorders is necessary, and may be facilitated by the use of animal models, in particular rodents. We sought to investigate whether the gerbil (Meriones unguiculatus) would be a good experimental model for the study of obesity and metabolic changes resulting from a diet rich in fats and sugars. Methods. 14 gerbils were divided according to weight into two experimental groups and received a a standard diet with 4,15kcal/g (CT; n = 7) or a diet rich in simple carbohydrates and fats with 5,86kcal/g (OB, n = 7) for 11 weeks. The animals had free access to water and food. The weight of each animal and food consumption of each cage were measured weekly and at the end of the experiment, blood, adipose tissue and liver were collected. The following parameters were determined: cholesterol (COL), triglycerides (TGL) and glycemia (GLI) in the plasma; cytokines (IL-6, IL-10 and TNF-α) and hormones (adiponectin and leptin) in adipose tissue; activity of superoxide dismutase (SOD) and catalase (CAT), extraction and differentiation of fat in the liver and liver histology. Results. The consumption of a diet rich in simple fats and carbohydrates led to an increase of total body weight, relative weights of liver and adipose tissue, glucose and triglycerides levels, and TNF-α concentration in adipose tissue. Animals of this group also showed a significant increase of total fat, cholesterol and triglyceride content in the liver, contributing to higher intensity of hepatic steatosis. On the other hand, depletion in the enzyme activity of SOD and CAT in the liver, as well as reduction of IL-10 and adiponectin levels were found in adipose tissue of these animals. Conclusion. Diet consumption consisting of an excess in saturated fat and simple carbohydrates establish the gerbil as an experimental model for the study of obesity and metabolic and liver abnormalities resulting from this disease.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hassan Sadri ◽  
Morteza Hosseini Ghaffari ◽  
Katharina Schuh ◽  
Christian Koch ◽  
Helga Sauerwein

AbstractOver-conditioned dairy cows, classified by body condition score (BCS) and backfat thickness (BFT) are less able to metabolically adapt to the rapidly increasing milk yield after parturition. Based on serum metabolome and cluster analyses, high BCS cows (HBCS) could be classified into metabotypes that are more similar to normal (NBCS) cows, i.e., HBCS predicted normal (HBCS-PN) than the HBCS predicted high (HBCS-PH) cows—similar to the concept of obese but metabolically healthy humans. Our objective was to compare muscle metabolome and mRNA abundance of genes related to lipogenesis and lipolysis in adipose tissue between HBCS-PH (n = 13), HBCS-PN (n = 6), and NBCS-PN (n = 15). Tail-head subcutaneous fat was biopsied on d −49, 3, 21, and 84 relative to parturition. Potential differences in the oxidative capacity of skeletal muscle were assessed by targeted metabolomics in M. semitendinosus from d 21. Besides characteristic changes with time, differences in the mRNA abundance were limited to lipogenesis-related genes on d −49 (HBCS-PH > HBCS-PN). The HBCS-PH had more than two-fold higher muscle concentrations of short (C2, C4-OH, C6-OH) and long-chain acylcarnitines (C16, C18, and C18:1) than HBCS-PN, indicating a greater oxidative capacity for fatty acids (and utilization of ketones) in muscle of HBCS-PN than HBCS-PH cows.


Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 40
Author(s):  
Anna Virginia Adriana Pirozzi ◽  
Paola Imbimbo ◽  
Antonella D’Agostino ◽  
Virginia Tirino ◽  
Rosario Finamore ◽  
...  

Several plant extracts are acquiring increasing value because of their antioxidant activity and hypolipidemic properties. Among them, great interest has been recently paid to açai fruit as a functional food. The aim of this study was to test the ability of açai extract in reducing oxidative stress and modulating lipid metabolism in vitro using different cell models and different types of stress. In fact, lipid peroxidation as evaluated in a HepG2 model was reduced five-fold when using 0.25 µg/mL of extract, and it was further reduced (20-fold) with the concentration increase up to 2.5 µg/mL. With the non alcoholic fatty liver disease (NAFLD)in vitro model, all concentrations tested showed at least a two-fold reduced fat deposit. In addition, primary adipocytes challenged with TNF-α under hypoxic conditions to mimic the persistent subcutaneous fat, treated with açai extract showed an approximately 40% reduction of fat deposit. Overall, our results show that açai is able to counteract oxidative states in all the cell models analysed and to prevent the accumulation of lipid droplets. No toxic effects and high stability overtime were highlighted at the concentrations tested. Therefore, açai can be considered a suitable support in the prevention of different alterations of lipid and oxidative metabolism responsible for fat deposition and metabolic pathological conditions.


2017 ◽  
Vol 55 (4) ◽  
pp. 212-221 ◽  
Author(s):  
Ashok Kumar Ahirwar ◽  
Archana Singh ◽  
Anju Jain ◽  
Surajeet Kumar Patra ◽  
Binita Goswami ◽  
...  

AbstractIntroduction. Endothelial dysfunction has been considered as one of the important factors in pathogenesis of Metabolic Syndrome (Met S). Subclinical hypothyroidism (SCH) has also been reported to be associated with Met S. The aim of our study is to evaluate the association of raised TSH with mediators of endothelial dysfunction in Met S with Subclinical hypothyroidism as compared to healthy controls.Methods. Study population consisted of 100 subjects, out of which 50 were cases of Met S and 50 were healthy controls. Met S group were further divided into two, based on the presence & absence of SCH. Serum insulin, T3, T4, TSH were measured by chemiluminescence based immunoassay (CLIA). Serum nitric oxide (NO) levels were measured by Modified Griess’s method and serum endothelin-1 (ET-1) levels were measured by ELISA.Results. Out of 50 cases of Met S, SCH was diagnosed in 22. The mean serum TSH levels were significantly higher in Met S cases as compared to healthy controls (5.7 ± 1.2 μIU/mL vs. 2.3 ± 1.6 μIU/mL, P <0.0001). Mean serum NO levels were significantly lower in Met S cases as compared to healthy control (15.4 ± 10 μM vs. 21 ± 10 μM, p = 0.009). Mean serum ET-1 levels were significantly higher in Met S cases as compared to healthy controls (2.68 ± 1.7 fmol/mL vs. 2.1 ± 0.84 fmol/mL, p = 0.011). On Pearson’s correlation analysis, TSH showed positive correlation with ET-1 (r = 0.341, p = 0.001) and negative correlation with NO (r = −0.331, p = 0.001). Binary logistic regression analysis showed that TSH, NO and ET-1 has significant odd’s ratio for predicting Met S.Conclusion. Met S cases were screened for thyroid abnormalities and found to have 44% of SCH along with co-existing endothelial dysfunction. Raised TSH in SCH could cause endothelial dysfunction which may lead to Met S and associated co-morbidities. Present study gives new insight in linking endothelial dysfunction and raised TSH in Met S. Therefore, Met S cases should be screened for SCH and treated appropriately to attenuate endothelial dysfunction and associated comorbidities in Met S.


Author(s):  
Petra C. Vinke ◽  
Milou H. H. S. Luitjens ◽  
Karlien A. Blijleven ◽  
Gerjan Navis ◽  
Daan Kromhout ◽  
...  

Abstract The identification of early-life determinants of overweight is crucial to start early prevention. As weight gain accelerates between 2 and 6 years, we studied the association between diet quality in children aged 3 years and the change in BMI and overweight incidence in the following 7 years. From the Dutch GECKO Drenthe birth cohort, 1001 children born in 2006 or 2007 with complete data on diet (food frequency questionnaire at the age of 3 years) and growth at the age of 3 and 10 years were included. Diet quality was estimated with the evidence-based Lifelines Diet Score (LLDS). Measured height and weight at the age of 3 and 10 years were used to calculate BMI z-scores standardized for age and sex. The associations of the LLDS (in quintiles) with BMI-z change and overweight incidence were studied with linear and logistic regression analyses. Overweight prevalence in the total study population increased from 8.3% at the age of 3 years to 16.7% at the age of 10 years. The increase in overweight prevalence ranged from 14.7% in Q1 to 3.5% in Q5. Children with a better diet quality (higher quintiles of LLDS) increased significantly less in BMI-z (confounder adjusted βLLDS = −0.064 (−0.101; −0.026)). Children with a poor diet quality at the age of 3 years had a considerably higher risk for overweight at the age of 10 years (confounder adjusted OR for Q1 vs. Q5 was 2.86 (95% CI 1.34–6.13). These results show the importance of diet in healthy development in the early life following the first 1000 days when new habits for a mature diet composed of food groups with lifelong importance are developed, providing a relevant window for overweight prevention early in life.


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