Abstract: 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 (EqASC) against mitochondrial dysfunction and inflammatory activation. 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). 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. [Image: see text] The online version contains supplementary material available at 10.1186/s12917-025-05033-y.
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Overview
This study investigates how sex hormone-binding globulin (SHBG) treatment can improve mitochondrial function and reduce inflammation in stem cells derived from horses with equine metabolic syndrome (EMS), a condition associated with obesity, insulin resistance, and inflammation.
The research highlights SHBG’s potential to restore cell metabolic health and modulate inflammatory responses, offering a promising therapeutic approach for EMS.
Introduction to Equine Metabolic Syndrome (EMS)
EMS is a common condition in horses characterized by:
Chronic low-grade inflammation
Dysfunction in mitochondrial dynamics and function
Increased risk of laminitis, a painful hoof disease
Associated metabolic disturbances include obesity, insulin resistance, and predisposition to diabetes.
SHBG, a protein that binds sex hormones in the bloodstream, is found at reduced levels in individuals with metabolic imbalances.
Rationale for SHBG Treatment
Decreased SHBG has been linked to higher risks of metabolic disorders such as obesity and diabetes.
This study hypothesized that administering SHBG externally might protect and improve cellular function in EMS-affected cells.
Specifically, the focus was on adipose-derived stem cells from EMS horses (EqASC) as a model for investigating mitochondrial and inflammatory status.
Methodology
Adipose-derived stem cells isolated from horses diagnosed with EMS were cultured.
Cells were treated with 50 nM concentrations of SHBG.
Post-treatment analyses included:
Cell viability assessments to ensure treatments were not toxic
Measurement of mitochondrial metabolism and dynamics markers
Gene expression profiling of inflammatory and anti-inflammatory cytokines
Key Findings
Mitochondrial Function Improvements:
SHBG increased mitochondrial flexibility, vital for adapting to cellular energy demands.
Upregulation of genes related to mitochondrial dynamics:
PARKIN and PINK1: involved in mitophagy, the removal of damaged mitochondria
Enhanced expression of genes related to mitoribosomes and the mitochondrial oxidative phosphorylation system, which are essential for energy production.
Reduction of Inflammation:
SHBG treatment decreased expression of pro-inflammatory cytokines:
IL-1β
IL-6
Increased expression of anti-inflammatory cytokine genes:
IL-10
IL-13
Implications of the Research
The findings suggest that SHBG has a protective role in counteracting EMS-related mitochondrial dysfunction and inflammation.
By improving mitochondrial health and reducing inflammation, SHBG could help restore normal metabolism in stem cells affected by EMS.
This lays the groundwork for considering SHBG as a therapeutic agent for managing EMS and potentially other metabolic disorders.
Future therapies could focus on modulating SHBG levels to improve equine metabolic health and reduce complications such as laminitis.
Overall Conclusion
The study provides strong evidence that SHBG administration improves key cellular functions related to energy metabolism and inflammation in EMS-affected equine stem cells.
These beneficial effects of SHBG support its potential use in developing novel treatments aimed at alleviating the pathological features of EMS.
Cite This Article
APA
Bourebaba N, Domagała J, Bourebaba L.
(2025).
Revitalizing equine metabolism: how SHBG improves mitochondrial function and reduces inflammation.
BMC Vet Res, 21(1), 620.
https://doi.org/10.1186/s12917-025-05033-y
Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, Wrocław, 50-375, Poland. nabila.bourebaba@upwr.edu.pl.
Domagała, Justyna
Department of Internal Medicine and Clinic of Diseases of Horses, Dogs and Cats, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Grunwaldzki Sq. 47, Bldg. B2, Room 1-207a, Wrocław, 50-366, Poland.
Bourebaba, Lynda
Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, Wrocław, 50-375, Poland. lynda.bourebaba@upwr.edu.pl.
Conflict of Interest Statement
Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
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