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

Abstract

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.

Expression of Steroid Receptor RNA Activator 1 (SRA1) in the Adipose Tissue Is Associated with TLRs and IRFs in Diabesity

“…TNFα also predicted SRA1 adipose expression in both normal weight and obese populations, regardless of diabetes status. Taken together, this study revealed specific association patterns of the adipose SRA1 expression with diverse immune markers, most of them being inflammatory by nature [ 42 ].…”

“…HbA1c levels of <5.7, 5.7–6.4%, and >6.4% represented normal, prediabetes, and diabetes status, respectively. Height, weight, waist and hip circumferences, BMI, and PBF were measured and calculated as previously described [ 42 ]. For the assessment of insulin resistance (HOMA-IR) and insulin sensitivity, fasting blood glucose and insulin levels were used to determine HOMA index [ 43 ].…”

“…The written informed consent was obtained from each participant at the time of enrolment in the study. The individuals with chronic diseases of the heart, liver, kidney, lung, or those with type 1 diabetes, immune dysfunction, hematologic disorders, pregnancy, or malignancy were excluded previously stated [ 42 , 44 ]. Clinical and demographic features of the study cohort are presented in Supplementary Table S1 .…”

“…Biopsies of the human adipose tissue, about 0.5 g in size, were collected from the abdominal subcutaneous adipose tissue, next to the umbilicus by using sterile surgical technique as described [ 42 , 45 ]. The sample was further cut into smaller pieces, about 50–100 mg in size, and added to RNAlater (Sigma-Aldrich Chemie GmbH, Taufkirchen, Germany) and stored at −80 °C until use for RNA extraction.…”

IL-1β and TNFα Cooperativity in Regulating IL-6 Expression in Adipocytes Depends on CREB Binding and H3K14 Acetylation

“…For each real-time PCR reaction, 50 ng of cDNA template was amplified using Inventoried TaqMan Gene Expression Assay products (mouse IL-6: Hs00446190_m1; 1) Pparg: Mm00440940_m1;Fabp4: Mm00445878_m1; mouse GAPDH:Mm99999915_g; human IL-6: Hs00985639_m1; Ppar g: Hs01115513_m1; PLIN2: Hs00605340_m1; 1; human GAPDH: 4310884E using two gene-specific primers, one TaqMan MGB probe (6-FAM dye-labeled), a TaqMan ® Gene Expression Master Mix (Applied Biosystems, Foster City, CA, USA), and a 7500 Fast Real-Time PCR System (Applied Biosystems, Foster City, CA, USA) [28][29][30][31]. The target mRNA levels were normalized against GAPDH mRNA relative to the control, and calculated using the 2 −∆∆CT method [32]. Relative mRNA expression was expressed as fold expression relative to the average of control gene expression.…”