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

Shihab Kochumon,Fahd Al-Mulla,Rasheed Ahmad,Jaakko Tuomilehto,Sardar Sindhu,Reeby Thomas,Steve Shenouda,Hossein Arefanian

doi:10.3390/cells10102602

Shihab Kochumon, Fahd Al-Mulla + Show 6 more

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https://doi.org/10.3390/cells10102602

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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.

Highlights

This article is an open access articleSRA1 is a gene that encodes steroid receptor RNA activator 1 (SRA1) [1]
We found that SRA1 expression was significantly higher (n = 28, 2.19 ± 0.62 fold, p = 0.015)
Obesity induces a state of chronic, low-grade inflammation in the adipose tissue that is accompanied by the local secretion of several pro-inflammatory cytokines and chemokines, especially TNFα, attenuating insulin action and resulting in insulin resistance through activation of the JNK pathway [20,34]

Summary

Introduction

This article is an open access articleSRA1 is a gene that encodes steroid receptor RNA activator 1 (SRA1) [1]. It was reported that SRA1 can modulate gene transcription in the cell- and system-specific manners [1,2,3,4]. Other proteins that bind either directly or indirectly to DNA and serves as a natural organizer, regulating multiple physiological functions that govern the epigenetic modifications, modulation of chromatin modification, and gene expressions [5,6,7]. Higher expression levels of SRA1 in the human liver, muscle tissues, and in white and brown adipose tissues as key organs in the regulation of metabolic homeostasis compared to other tissues have been reported [1,8,13]. SRA1 is known to be associated with several diseases, including obesity, cardiovascular diseases, polycystic ovary syndrome (PCOS), laryngeal squamous cell carcinoma, and breast cancer [3,8,9,10,13,14,15,16,17]

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