Revitalizing equine metabolism: how SHBG improves mitochondrial function and reduces inflammation

Abstract

Background: Equine metabolic syndrome (EMS) is associated with chronic low-grade inflammation, disruptions in mitochondrial dynamics and function, and an increased risk of developing laminitis. Recent research has highlighted that reduced levels of sex hormone-binding globulin (SHBG) in the bloodstream are linked to higher susceptibility to obesity, insulin resistance, and diabetes, potentially contributing to broader metabolic imbalances. This study aimed to evaluate whether exogenously administered SHBG could protect adipose-derived stem cells from horses affected by EMS (EqASCEMS) against mitochondrial dysfunction and inflammatory activation. Results: Following treatment with 50 nM of SHBG, analyses were conducted to assess cell viability, mitochondrial metabolism and dynamics, as well as the expression of inflammatory and anti-inflammatory markers. Results showed that SHBG significantly enhanced mitochondrial flexibility, as indicated by the upregulation of MFN-1, PARKIN, and PINK genes. SHBG also positively influenced the expression of genes related to mitoribosomes and the mitochondrial oxidative phosphorylation (OXPHOS) system. In addition, SHBG treatment markedly reduced EMS-induced inflammation by decreasing pro-inflammatory cytokines such as IL-1β as well as IL-6 and boosting anti-inflammatory cytokines gene expression (IL-10 and IL-13). Conclusion: Our findings suggest that SHBG exerts beneficial effects on the metabolic function of stem cells affected by EMS and holds promise as a potential therapeutic agent in the development of effective treatment strategies for this condition.