Abstract
Endocrine disorders are becoming an increasing problem in both human and veterinary medicine. In recent years, more and more horses worldwide have been suffering from equine metabolic syndrome (EMS). This metabolic disorder is characterized by pathological obesity, hyperinsulinaemia, hyperglycaemia and insulin resistance. Although metabolic disorders, including diabetes, have been extensively studied, there are still no data on the molecular effects of EMS in horses. Thus, the aim of this study was to evaluate apoptosis, oxidative stress, autophagy and microRNA (miR) expression in multipotent intestinal epithelial stem cells (IECs) and pancreatic islets (PIs) isolated post mortem form healthy and EMS diagnosed horses. Our group was the first to describe how EMS affects IEC and PI aging and senescence. First, we evaluated isolation and culture protocol for these cells and subsequently established their metabolic status in vitro. Both IECs and PIs isolated from EMS horses were characterized by increased apoptosis and senescence. Moreover, they accumulated elevated levels of reactive oxygen species (ROS). Here we have observed that autophagy/mitophagy may be a protective mechanism which allows those cells to maintain their physiological function, clear protein aggregates and remove damaged organelles. Furthermore, it may play a crucial role in reducing endoplasmic reticulum (ER) stress. This protective mechanism may help to overcome the harmful effects of ROS and provide building blocks for protein and ATP synthesis.
Highlights
Equine metabolic syndrome (EMS) has become one of the most frequent endocrine disorders in large animal veterinary medicine, especially in modern and developed countries [1]
Insulin resistance and laminitis are the cardinal signs of EMS phenotype, and all, when not properly treated, lead to devastation of the body and sometimes necessitate euthanasia
Adipose tissue inflammation leads to the deterioration of adipose stromal stem cells (ASCs), impairing their physiological functions and causing their senescence [5,6,7]
Summary
Equine metabolic syndrome (EMS) has become one of the most frequent endocrine disorders in large animal veterinary medicine, especially in modern and developed countries [1]. SSiimmiillaarrllyy,, tthhee aammoouunntt ooff NNOO wwaass aallssoo oobbsseerrvveedd ttoo bbee iinnccrreeaasseedd iinn tthhoossee cceellllss ((FFiigguurree 99BB)). Another study showed that elevated free fatty acids or glucose levels increased apoptosis in rat pancreatic islets, and these cytotoxic effects could be mediated by oxidative stress This could contribute to the beta-cell failure that occurred in most T2D patients a few years after the onset of clinical diabetes [44]. In the present study we have revealed that both IECs and PIs isolated from EMS individuals are characterized by deterioration in cellular physiology Those cells displayed increased apoptosis, senescence, autophagy, mitochondrial function deterioration and ROS accumulation. The obtained findings suggest that antioxidants might exert therapeutic effects in the prevention and management of diabetes, and the supplementation of EMS horses’ diet with antioxidants seems to be highly reasonable and may alleviate EMS symptoms
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