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Frontiers in molecular biosciences2023; 10; 1214961; doi: 10.3389/fmolb.2023.1214961

Sex hormone-binding globulin improves lipid metabolism and reduces inflammation in subcutaneous adipose tissue of metabolic syndrome-affected horses.

Abstract: Equine metabolic syndrome (EMS) is a steadily growing endocrine disorder representing a real challenge in veterinary practice. As a multifactorial condition, EMS is characterized by three main metabolic abnormalities including insulin resistance, increased adiposity or obesity and hoof laminitis. Adipose tissue dysfunction is recognized as a core pathophysiological determinant of EMS, as it strongly participates to lipotoxicity and systemic metaflammation, both of which have been closely linked to the development of generalized insulin resistance. Besides, sex hormone binding globulin (SHBG) is an important sex steroids transporters that has been recently proposed as an important metabolic mediator. Therefore, the aim of this study was to verify whether SHBG treatment may ameliorate subcutaneous adipose tissue metabolic failure under EMS condition in terms of lipidome homeostasis, lipid metabolism programs, insulin signalling and local inflammation. Subcutaneous adipose tissue (SAT) biopsies were collected post-mortem from healthy (n = 3) and EMS (n = 3) slaughtered horses. SHBG protein has been applied to SAT samples from EMS horses for 24 h at a final concentration of 50 nM, while control groups (healthy and untreated EMS) were cultured in the presence of SHBG-vehicle only. Tissues from all groups were afterwards secured for downstream analysis of gene expression using RT-qPCR, protein levels by Western blot and ELISA assay and lipidomics through GC-MS technique. Obtained results showcased that SHBG intervention efficiently normalized the altered fatty acids (FAs) profiles by lowering the accumulation of saturated and trans FAs, as well as the pro-inflammatory arachidonic and linoleic acids. Moreover, SHBG showed promising value for the regulation of adipocyte lipolysis and engorgement by lowering the levels of perilipin-1. SHBG exerted moderated effect toward SCD1 and FASN enzymes expression, but increased the LPL abundance. Interestingly, SHBG exhibited a negative regulatory effect on pro-adipogenic stimulators and induced higher expression of KLF3, IRF3 and β-catenin, known as strong adipogenesis repressors. Finally, SHBG protein showed remarkable ability in restoring the insulin signal transduction, IR/IRS/Pi3K/AKT phosphorylation events and GLUT4 transporter abundance, and further attenuate pro-inflammatory response by lowering IL-6 tissue levels and targeting the PDIA3/ERK axis. Overall, the obtained data clearly demonstrate the benefice of SHBG treatment in the regulation of adipose tissue metabolism in the course of EMS and provide new insights for the development of molecular therapies with potential translational application to human metabolic disorders.
Copyright © 2023 Bourebaba, Kępska, Qasem, Zyzak, Łyczko, Klemens, Mularczyk and Marycz.
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Publication Date: 2023-12-11 PubMed ID: 38146533PubMed Central: PMC10749534DOI: 10.3389/fmolb.2023.1214961Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates the effects of sex hormone-binding globulin (SHBG) on the metabolic failures of subcutaneous adipose tissue in horses affected by Equine metabolic syndrome (EMS). It finds that SHBG can potentially improve lipid metabolism, insulin signalling, and reduce inflammation, thus providing new insights for the development of therapies for human metabolic disorders.

Study Context

  • The research focuses on Equine Metabolic Syndrome (EMS), a complex and increasingly common endocrine disorder in horses. EMS is identified by insulin resistance, increased adiposity or obesity, and hoof laminitis.
  • Disruptions in adipose tissue function contribute significantly to EMS, leading to lipotoxicity and systemic metaflammation, which in turn result in widespread insulin resistance.
  • Sex hormone-binding globulin (SHBG), a transporter for sex steroids, has recently been suggested to be an important mediator for metabolism.
  • The researchers in this study sought to determine if SHBG could improve the metabolic failure in subcutaneous adipose tissue in horses with EMS, specifically looking at lipid homeostasis, lipid metabolism, insulin signalling, and local inflammation.

Methodology

  • Post-mortem subcutaneous adipose tissue (SAT) samples were collected from both healthy and EMS-affected horses.
  • SHBG protein was introduced to the EMS-affected horse samples, while the control groups (healthy and untreated EMS) were cultured with only the SHBG carrier.
  • Subsequently, all samples were analyzed to assess gene expression, protein levels, and lipidomics.

Findings

  • The results showed that SHBG treatment effectively normalized fatty acid (FA) profiles, reducing the buildup of saturated and trans FAs, as well as arachidonic and linoleic acids which can cause inflammation.
  • SHBG demonstrated potential in controlling adipocyte lipolysis and engorgement by reducing perilipin-1 levels. It also had a moderated effect on SCD1 and FASN enzymes expression and increased the quantity of LPL.
  • SHBG resulted in a suppressive effect on pro-adipogenic stimulators and triggered a higher expression of known adipogenesis repressors like KLF3, IRF3, and β-catenin.
  • Notably, SHBG significantly restored insulin signal transduction, IR/IRS/Pi3K/AKT phosphorylation events, and GLUT4 transporter abundance.
  • It was also found to significantly mitigate pro-inflammatory response by reducing IL-6 tissue levels and targeting the PDIA3/ERK axis.

Conclusions

  • The data demonstrates the potential benefits of SHBG treatment in regulating adipose tissue metabolism in the face of EMS.
  • These findings could also offer new insights for creating molecular therapies, with the possibility of translating these to treatments for human metabolic disorders.

Cite This Article

APA
Bourebaba L, Kępska M, Qasem B, Zyzak M, Łyczko J, Klemens M, Mularczyk M, Marycz K. (2023). Sex hormone-binding globulin improves lipid metabolism and reduces inflammation in subcutaneous adipose tissue of metabolic syndrome-affected horses. Front Mol Biosci, 10, 1214961. https://doi.org/10.3389/fmolb.2023.1214961

Publication

Frontiers in molecular biosciences
ISSN: 2296-889X
NlmUniqueID: 101653173
Country: Switzerland
Language: English
Volume: 10
Pages: 1214961

Researcher Affiliations

Bourebaba, Lynda
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
Kępska, Martyna
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
Qasem, Badr
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
Zyzak, Magdalena
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
Łyczko, Jacek
  • Department of Food Chemistry and Biocatalysis, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
Klemens, Marta
  • Department of Food Chemistry and Biocatalysis, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
Mularczyk, Malwina
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
  • International Institute of Translational Medicine, Wisznia Mała, Poland.
Marycz, Krzysztof
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
  • International Institute of Translational Medicine, Wisznia Mała, Poland.
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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