Sex hormone-binding globulin (SHBG) mitigates ER stress and improves viability and insulin sensitivity in adipose-derived mesenchymal stem cells (ASC) of equine metabolic syndrome (EMS)-affected horses
Authors: Nabila Bourebaba, Mateusz Sikora, B. Qasem, Lynda Bourebaba, Krzysztof Marycz
Journal: Cell Communication and Signaling : CCS
Summary
# Editorial Summary Equine metabolic syndrome remains a significant welfare and performance concern, characterised by insulin resistance, chronic low-grade inflammation and increased laminitis risk, yet therapeutic options remain limited. Researchers investigated whether exogenous sex hormone-binding globulin (SHBG)—a circulating protein known to correlate with metabolic health in humans—could ameliorate dysfunction in adipose-derived mesenchymal stem cells harvested from EMS-affected horses, testing two concentrations (50 and 100 nM) across 24–72-hour treatment periods and measuring cell viability, apoptosis, oxidative stress markers, endoplasmic reticulum (ER) stress indicators, and insulin signalling pathways. SHBG treatment substantially improved cell survival by suppressing pro-apoptotic mediators (p53 and p21), reduced reactive oxygen species accumulation through upregulation of antioxidant enzymes (SOD1, catalase, glutathione peroxidase) and nitric oxide modulation, alleviated ER stress via microRNA-7a-5p upregulation and restoration of protein chaperone function, and crucially restored insulin sensitivity through PI3K/Akt/GLUT4 pathway activation. These findings suggest SHBG may represent a novel therapeutic avenue for addressing the underlying cellular dysfunction in EMS, potentially offering a pathway toward adjunctive treatments that target metabolic dysregulation at the cellular level rather than managing symptoms alone; however, translation to in vivo efficacy and optimal dosing strategies in clinical settings will require further investigation.
Read the full abstract on PubMed
Practical Takeaways
- •SHBG may represent a novel therapeutic target for treating equine metabolic syndrome by improving cellular insulin sensitivity and reducing metabolic dysfunction at the molecular level
- •This in vitro research provides foundational evidence for potential future clinical trials investigating SHBG as a treatment for EMS, but in vivo studies are needed before clinical application
- •Understanding the mechanisms by which SHBG improves stem cell function in EMS could inform development of more targeted therapeutic protocols for insulin-resistant horses
Key Findings
- •Exogenous SHBG treatment at 50-100 nM significantly promoted adipose-derived stem cell proliferation and survival in EMS-affected horses by reducing pro-apoptotic markers p53 and p21
- •SHBG reduced oxidative stress and intracellular reactive oxygen species (ROS) accumulation by upregulating antioxidant enzymes (SOD1, CAT, GPx) and modulating nitric oxide levels
- •SHBG treatment alleviated endoplasmic reticulum (ER) stress through upregulation of miR-7a-5p and restoration of PDIA3 chaperone protein, with decreased ATF-6, CHOP, and eIF2α expression
- •SHBG substantially improved insulin sensitivity by modulating the Pi3K/Akt/Glut4 insulin signalling cascade in EMS adipose-derived stem cells