Sex hormone-binding globulin (SHBG) enhances mitochondrial dynamics and biogenesis while attenuating inflammation in adipose-derived mesenchymal stem cells (ASCs) derived from equine metabolic syndrome (EMS)-affected horses.

Equine metabolic syndrome (EMS) is a prevalent endocrine disorder affecting horses, ponies and donkeys, characterized by dysregulated mitochondrial dynamics, chronic low-grade inflammation, and an increased susceptibility to laminitis. EMS poses significant health risks and is associated with obesity, insulin resistance, and diabetes. Recent studies have shown that low serum levels of sex hormone-binding globulin (SHBG) are linked to these metabolic dysregulations. To investigate whether exogenous SHBG could ameliorate mitochondrial dysfunction and inflammation in adipose-derived stromal stem cells from EMS-affected horses (EqASCEMS), we conducted a comprehensive study. EqASCEMS cultures were treated with 50 nM of SHBG for 24 hours. We evaluated various parameters including mitochondrial dynamics and biogenesis as well as the expression of pro-inflammatory and anti-inflammatory markers. Our findings demonstrated that exogenous SHBG treatment significantly enhanced mitochondrial biogenesis. This enhancement was evidenced by increased expression of key genes and proteins associated with mitochondrial dynamics, such as MFN, PARKIN, PINK, Cytochrome C, as well as genes related to mitoribosomes and the mitochondrial oxidative phosphorylation system (NDUFA9, COX4L1, COX4L2 and MTERF4). Furthermore, SHBG exhibited anti-inflammatory properties by reducing the expression of pro-inflammatory cytokine genes (IL-1β, IL-6, TNF-α) and promoting the expression of anti-inflammatory markers (IL-4, IL-10, IL-13) in EqASCEMS. Our study highlights the potential therapeutic value of SHBG in modulating ASC metabolic activities and suggests its importance as a target for the development of effective treatment protocols for EMS. These findings provide valuable insights into mitigating the metabolic and inflammatory consequences of EMS in horses, potentially improving their overall health and well-being.