The Experts below are selected from a list of 351 Experts worldwide ranked by ideXlab platform
Krzysztof Marycz - One of the best experts on this subject based on the ideXlab platform.
-
cladophora glomerata methanolic extract promotes chondrogenic gene expression and cartilage phenotype differentiation in Equine adipose derived mesenchymal stromal stem cells affected by Metabolic Syndrome
Stem Cell Research & Therapy, 2019Co-Authors: Krzysztof Marycz, Izabela Michalak, Lynda Bourebaba, Meriem Baouche, Katarzyna KucharczykAbstract:Chondrogenesis represents a highly dynamic cellular process that leads to the establishment of various types of cartilage. However, when stress-related injuries occur, a rapid and efficient regeneration of the tissues is necessary to maintain cartilage integrity. Mesenchymal stem cells (MSCs) are known to exhibit high capacity for self-renewal and pluripotency effects, and thus play a pivotal role in the repair and regeneration of damaged cartilage. On the other hand, the influence of certain pathological conditions such as Metabolic disorders on MSCs can seriously impair their regenerative properties and thus reduce their therapeutic potential. In this investigation, we attempted to improve and potentiate the in vitro chondrogenic ability of adipose-derived mesenchymal stromal stem cells (ASCs) isolated from horses suffering from Metabolic Syndrome. Cultured cells in chondrogenic-inductive medium supplemented with Cladophora glomerata methanolic extract were experimented for expression of the main genes and microRNAs involved in the differentiation process using RT-PCR, for their morphological changes through confocal and scanning electron microscopy and for their physiological homeostasis. The different added concentrations of C. glomerata extract to the basic chondrogenic inductive culture medium promoted the proliferation of Equine Metabolic Syndrome ASCs (ASCsEMS) and resulted in chondrogenic phenotype differentiation and higher mRNA expression of collagen type II, aggrecan, cartilage oligomeric matrix protein, and Sox9 among others. The results reveal an obvious inhibitory effect of hypertrophy and a strong repression of miR-145-5p, miR-146-3p, and miR-34a and miR-449a largely involved in cartilage degradation. Treated cells additionally exhibited significant reduced apoptosis and oxidative stress, as well as promoted viability and mitochondrial potentiation. Chondrogenesis in EqASCsEMS was found to be prominent after chondrogenic induction in conditions containing C. glomerata extract, suggesting that the macroalgae could be considered for the enhancement of ASC cultures and their reparative properties.
-
Systemic Administration of Rejuvenated Adipose-Derived Mesenchymal Stem Cells Improves Liver Metabolism in Equine Metabolic Syndrome (EMS)- New Approach in Veterinary Regenerative Medicine
Stem Cell Reviews and Reports, 2019Co-Authors: Krzysztof Marycz, F. Geburek, J. Szłapka-kosarzewska, Katarzyna Kornicka-garbowskaAbstract:Equine Metabolic Syndrome (EMS) is characterized by adiposity, insulin dysregulation and increased risk for laminitis. Increased levels of specific liver enzymes in the peripheral blood are typical findings in horses diagnosed with EMS. Current management of EMS is based on caloric restriction and increased physical activity. However, new potential treatment options are arising such as the transplantation of autologous adipose stem cells (ASC). However, cytophysiological properties of ASC derived from EMS horses are impaired which strongly limits their therapeutic potential. We hypothesized, that in vitro pharmacotherapy of those cells with 5-azacytidine (AZA) and resveratrol (RES) before their clinical application can reverse the aged phenotype of those cells and improve clinical outcome of autologous therapy. A 9 year old Dutch Warmblood Horse used for driving, was presented with severe obesity, insulin resistance. After EMS diagnosis, the animal received three intravenous injections of autologous, AZA/RES treated ASCs at weekly intervals. The therapeutic effect was assessed by the analysis of liver specific enzymes in the blood. ASC-transplantation reduced levels of glutamate dehydrogenase (GLDH), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH) and aspartate transaminase (AST). This case report demonstrates the therapeutic potential of this intervention for EMS as well as apt utility of autologous, rejuvenated ASC injections.
-
nortropane alkaloids as pharmacological chaperones in the rescue of Equine adipose derived mesenchymal stromal stem cells affected by Metabolic Syndrome through mitochondrial potentiation endoplasmic reticulum stress mitigation and insulin resistance
Stem Cell Research & Therapy, 2019Co-Authors: Krzysztof Marycz, Lynda Bourebaba, Fatiha Bedjou, Michael RockenAbstract:Equine Metabolic Syndrome (EMS) refers to a cluster of associated abnormalities and Metabolic disorders, including insulin resistance and adiposity. The numerous biological properties of mesenchymal stem cells (MSCs), including self-renewal and multipotency, have been the subject of many in-depth studies, for the management of EMS; however, it has been shown that this cell type may be affected by the condition, impairing thus seriously their therapeutic potential. Therefore, an attempt to rescue EMS adipose-derived stem cells (ASCs) with calystegines (polyhydroxylated alkaloids) that are endowed with strong antioxidant and antidiabetic abilities was performed. ASCs isolated from EMS horses were subsequently treated with various concentrations of total calystegines. Different parameters were then assessed using flow cytometry, confocal as well as SE microscopy, and RT-qPCR. Our results clearly demonstrated that calystegines could improve EqASC viability and proliferation and significantly reduce apoptosis, via improvement of mitochondrial potentiation and functionality, regulation of pro- and anti-apoptotic pathways, and suppression of ER stress. Furthermore, nortropanes positively upregulated GLUT4 and IRS transcripts, indicating a possible sensitizing or mimetic effect to insulin. Most interesting finding in this investigation lies in the modulatory effect of autophagy, a process that allows the maintenance of cellular homeostasis; calystegines acted as pharmacological chaperones to promote cell survival. Obtained data open new perspectives in the development of new drugs, which may improve the Metabolic dynamics of cells challenged by MS.
-
metformin increases proliferative activity and viability of multipotent stromal stem cells isolated from adipose tissue derived from horses with Equine Metabolic Syndrome
Cells, 2019Co-Authors: Agnieszka Smieszek, Katarzyna Kornicka, Jolanta Szlapkakosarzewska, Peter Androvic, Lukas Valihrach, Lucie Langerova, Eva Rohlova, Mikael Kubista, Krzysztof MaryczAbstract:In this study, we investigated the influence of metformin (MF) on proliferation and viability of adipose-derived stromal cells isolated from horses (EqASCs). We determined the effect of metformin on cell metabolism in terms of mitochondrial metabolism and oxidative status. Our purpose was to evaluate the metformin effect on cells derived from healthy horses (EqASCHE) and individuals affected by Equine Metabolic Syndrome (EqASCEMS). The cells were treated with 0.5 μM MF for 72 h. The proliferative activity was evaluated based on the measurement of BrdU incorporation during DNA synthesis, as well as population doubling time rate (PDT) and distribution of EqASCs in the cell cycle. The influence of metformin on EqASC viability was determined in relation to apoptosis profile, mitochondrial membrane potential, oxidative stress markers and BAX/BCL-2 mRNA ratio. Further, we were interested in possibility of metformin affecting the Wnt3a signalling pathway and, thus, we determined mRNA and protein level of WNT3A and β-catenin. Finally, using a two-tailed RT-qPCR method, we investigated the expression of miR-16-5p, miR-21-5p, miR-29a-3p, miR-140-3p and miR-145-5p. Obtained results indicate pro-proliferative and anti-apoptotic effects of metformin on EqASCs. In this study, MF significantly improved proliferation of EqASCs, which manifested in increased synthesis of DNA and lowered PDT value. Additionally, metformin improved metabolism and viability of cells, which correlated with higher mitochondrial membrane potential, reduced apoptosis and increased WNT3A/β-catenin expression. Metformin modulates the miRNA expression differently in EqASCHE and EqASCEMS. Metformin may be used as a preconditioning agent which stimulates proliferative activity and viability of EqASCs.
-
characterization of apoptosis autophagy and oxidative stress in pancreatic islets cells and intestinal epithelial cells isolated from Equine Metabolic Syndrome ems horses
International Journal of Molecular Sciences, 2018Co-Authors: Katarzyna Kornicka, Krzysztof Marycz, Agnieszka śmieszek, Jolanta Szlapkakosarzewska, Jennifer Irwin M Houston, Michael RoeckenAbstract: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.
Katarzyna Kornicka - One of the best experts on this subject based on the ideXlab platform.
-
metformin increases proliferative activity and viability of multipotent stromal stem cells isolated from adipose tissue derived from horses with Equine Metabolic Syndrome
Cells, 2019Co-Authors: Agnieszka Smieszek, Katarzyna Kornicka, Jolanta Szlapkakosarzewska, Peter Androvic, Lukas Valihrach, Lucie Langerova, Eva Rohlova, Mikael Kubista, Krzysztof MaryczAbstract:In this study, we investigated the influence of metformin (MF) on proliferation and viability of adipose-derived stromal cells isolated from horses (EqASCs). We determined the effect of metformin on cell metabolism in terms of mitochondrial metabolism and oxidative status. Our purpose was to evaluate the metformin effect on cells derived from healthy horses (EqASCHE) and individuals affected by Equine Metabolic Syndrome (EqASCEMS). The cells were treated with 0.5 μM MF for 72 h. The proliferative activity was evaluated based on the measurement of BrdU incorporation during DNA synthesis, as well as population doubling time rate (PDT) and distribution of EqASCs in the cell cycle. The influence of metformin on EqASC viability was determined in relation to apoptosis profile, mitochondrial membrane potential, oxidative stress markers and BAX/BCL-2 mRNA ratio. Further, we were interested in possibility of metformin affecting the Wnt3a signalling pathway and, thus, we determined mRNA and protein level of WNT3A and β-catenin. Finally, using a two-tailed RT-qPCR method, we investigated the expression of miR-16-5p, miR-21-5p, miR-29a-3p, miR-140-3p and miR-145-5p. Obtained results indicate pro-proliferative and anti-apoptotic effects of metformin on EqASCs. In this study, MF significantly improved proliferation of EqASCs, which manifested in increased synthesis of DNA and lowered PDT value. Additionally, metformin improved metabolism and viability of cells, which correlated with higher mitochondrial membrane potential, reduced apoptosis and increased WNT3A/β-catenin expression. Metformin modulates the miRNA expression differently in EqASCHE and EqASCEMS. Metformin may be used as a preconditioning agent which stimulates proliferative activity and viability of EqASCs.
-
characterization of apoptosis autophagy and oxidative stress in pancreatic islets cells and intestinal epithelial cells isolated from Equine Metabolic Syndrome ems horses
International Journal of Molecular Sciences, 2018Co-Authors: Katarzyna Kornicka, Krzysztof Marycz, Agnieszka śmieszek, Jolanta Szlapkakosarzewska, Jennifer Irwin M Houston, Michael RoeckenAbstract: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.
-
evaluation of oxidative stress and mitophagy during adipogenic differentiation of adipose derived stem cells isolated from Equine Metabolic Syndrome ems horses
Stem Cells International, 2018Co-Authors: Krzysztof Marycz, Agnieszka śmieszek, Christine Weiss, Katarzyna KornickaAbstract:Mesenchymal stem cells (MSCs) are frequently used in both human and veterinary medicine because their unique properties, such as modulating the immune response and differentiating into multiple lineages, make them a valuable tool in cell-based therapies. However, many studies have indicated the age-, lifestyle-, and disease-related deterioration of MSC regenerative characteristics. However, it still needs to be elucidated how the patient's health status affects the effectiveness of MSC differentiation. In the present study, we isolated mesenchymal stem cells from adipose tissue (adipose-derived mesenchymal stem cells (ASCs)) from horses diagnosed with Equine Metabolic Syndrome (EMS), a common Metabolic disorder characterized by pathological obesity and insulin resistance. We investigated the Metabolic status of isolated cells during adipogenic differentiation using multiple research methods, such as flow cytometry, PCR, immunofluorescence, or transmission and confocal microscopy. The results indicated the impaired differentiation potential of ASCEMS. Excessive ROS accumulation and ER stress are most likely the major factors limiting the multipotency of these cells. However, we observed autophagic flux during differentiation as a protective mechanism that allows cells to maintain homeostasis and remove dysfunctional mitochondria.
-
advanced nutritional and stem cells approaches to prevent Equine Metabolic Syndrome
Research in Veterinary Science, 2018Co-Authors: Krzysztof Marycz, Izabela Michalak, Katarzyna KornickaAbstract:Horses Metabolic disorders have become an important problem of modern veterinary medicine. Pathological obesity, insulin resistance and predisposition toward laminitis are associated with Equine Metabolic Syndrome (EMS). Based on pathogenesis of EMS, dietary and cell therapy management may significantly reduce development of this disorder. Special attention has been paid to the diet supplementation with highly bioavailable minerals and mesenchymal stem cells (MSC) which increase insulin sensitivity. In nutrition, there is a great interests in natural algae enriched via biosorption process with micro- and macroelements. In the case of cellular therapy, Metabolic condition of engrafted cells may be crucial for the effectiveness of the therapy. Although, recent studies indicated on MSC deterioration in EMS individuals. Here, we described the combined nutritional and stem cells therapy for the EMS treatment. Moreover, we specified in details how EMS affects the adipose-derived stem cells (ASC) population. Presented here, combined kind of therapy- an innovative and cutting edge approach of Metabolic disorders treatment may become a new gold standard in personalized veterinary medicine.
-
spirulina platensis improves mitochondrial function impaired by elevated oxidative stress in adipose derived mesenchymal stromal cells ascs and intestinal epithelial cells iecs and enhances insulin sensitivity in Equine Metabolic Syndrome ems horses
Marine Drugs, 2017Co-Authors: Daria Nawrocka, Katarzyna Kornicka, Agnieszka śmieszek, Krzysztof MaryczAbstract:Equine Metabolic Syndrome (EMS) is a steadily growing life-threatening endocrine disorder linked to insulin resistance, oxidative stress, and systemic inflammation. Inflammatory microenvironment of adipose tissue constitutes the direct tissue milieu for various cell populations, including adipose-derived mesenchymal stromal cells (ASCs), widely considered as a potential therapeutic cell source in the course of the treatment of Metabolic disorders. Moreover, elevated oxidative stress induces inflammation in intestinal epithelial cells (IECs)-the first-line cells exposed to dietary compounds. In the conducted research, we showed that in vitro application of Spirulina platensis contributes to the restoration of ASCs' and IECs' morphology and function through the reduction of cellular oxidative stress and inflammation. Enhanced viability, suppressed senescence, and improved proliferation of ASCs and IECs isolated from Metabolic Syndrome-affected individuals were evident following exposition to Spirulina. A protective effect of the investigated extract against mitochondrial dysfunction and degeneration was also observed. Moreover, our data demonstrate that Spirulina extract effectively suppressed LPS-induced inflammatory responses in macrophages. In vivo studies showed that horses fed with a diet based on Spirulina platensis supplementation lost weight and their insulin sensitivity improved. Thus, our results indicate the engagement of Spirulina platensis nourishing as an interesting alternative approach for supporting the conventional treatment of Equine Metabolic Syndrome.
Molly E Mccue - One of the best experts on this subject based on the ideXlab platform.
-
Assessment of the FAM174A 11G allele as a risk allele for Equine Metabolic Syndrome.
Animal genetics, 2020Co-Authors: M. M. Roy, Nichol Schultz, E M Norton, Aaron Rendahl, James R Mickelson, Dianne Mcfarlane, Raymond J. Geor, Molly E MccueAbstract:An 11G nucleotide repeat in the 3' UTR of FAM174A was recently postulated as a risk allele with a dominant mode of inheritance for Equine Metabolic Syndrome (EMS) and laminitis status in Arabian horses. The objective of this project was to evaluate this hypothesis in a large and diverse across-breed population. A total of 301 ponies, 292 Morgans, 64 Arabians, 49 Tennessee Walking Horses and 59 Quarter Horses were genotyped for six observed G repeat alleles in the FAM174A 3' UTR. Phenotype data included laminitis status, baseline insulin, glucose, non-esterified fatty acids, triglycerides, adiponectin, leptin, ACTH, insulin and glucose post oral sugar test, and two proxies for insulin resistance. The 11G allele frequencies were 18.8, 6.9, 1.8, 0.2 and 0.0% in the Arabians, Tennessee Walkers, ponies, Morgans and Quarter Horses respectively. Association analyses between FAM174A genotype and EMS phenotypes, and between allele count and EMS phenotypes, identified no statistically significant associations. When a dominant effect for the 11G allele was evaluated, a statistically significant association with adiponectin levels was identified in the ponies, and pairwise comparisons revealed that the estimated marginal means were higher in ponies with the 11G allele vs. alternative alleles (i.e. the allele had a protective effect). In conclusion, our data do not support the FAM174A 11G allele as a risk allele for EMS in our studied breeds.
-
genome wide association analyses of Equine Metabolic Syndrome phenotypes in welsh ponies and morgan horses
Genes, 2019Co-Authors: E M Norton, Nichol Schultz, R J Geor, James R Mickelson, Dianne Mcfarlane, Molly E MccueAbstract:Equine Metabolic Syndrome (EMS) is a complex trait for which few genetic studies have been published. Our study objectives were to perform within breed genome-wide association analyses (GWA) to identify associated loci in two high-risk breeds, coupled with meta-analysis to identify shared and unique loci between breeds. GWA for 12 EMS traits identified 303 and 142 associated genomic regions in 264 Welsh ponies and 286 Morgan horses, respectively. Meta-analysis demonstrated that 65 GWA regions were shared across breeds. Region boundaries were defined based on a fixed-size or the breakdown of linkage disequilibrium, and prioritized if they were: shared between breeds or across traits (high priority), identified in a single GWA cohort (medium priority), or shared across traits with no SNPs reaching genome-wide significance (low priority), resulting in 56 high, 26 medium, and seven low priority regions including 1853 candidate genes in the Welsh ponies; and 39 high, eight medium, and nine low priority regions including 1167 candidate genes in the Morgans. The prioritized regions contained protein-coding genes which were functionally enriched for pathways associated with inflammation, glucose metabolism, or lipid metabolism. These data demonstrate that EMS is a polygenic trait with breed-specific risk alleles as well as those shared across breeds.
-
heritability of Metabolic traits associated with Equine Metabolic Syndrome in welsh ponies and morgan horses
Equine Veterinary Journal, 2019Co-Authors: E M Norton, Nichol Schultz, Aaron Rendahl, R J Geor, James R Mickelson, Dianne Mcfarlane, Molly E MccueAbstract:BACKGROUND: Equine Metabolic Syndrome (EMS) is a complex clinical disorder with both environmental and genetic factors contributing to EMS phenotypes. Estimates of heritability determine the proportion of variation in a trait that is attributable to genetics. OBJECTIVES: To provide heritability estimates for nine Metabolic traits associated with EMS in two high‐risk breeds. STUDY DESIGN: Retrospective cohort study. METHODS: High‐density single‐nucleotide polymorphism (SNP) genotype data was used to estimate the heritability (h²SNP) of nine Metabolic traits relevant to EMS in a cohort of 264 Welsh ponies and 286 Morgan horses. Traits included measurements of insulin, glucose, non‐esterified fatty acids (NEFA), triglycerides, leptin, adiponectin, ACTH, and glucose (GLU‐OST) and insulin (INS‐OST) following an oral sugar challenge. RESULTS: In Welsh ponies, seven of the nine traits had statistically significant h²SNP estimates that were considered moderately to highly heritable (h²SNP>0.20) including: triglycerides (0.313; s.e. = 0.146), glucose (0.408; s.e. = 0.135), NEFA (0.434; s.e. = 0.136), INS‐OST (0.440; s.e. = 0.148), adiponectin (0.488; s.e. = 0.143), leptin (0.554; s.e. = 0.132) and insulin (0.808; s.e. = 0.108). In Morgans, six of the nine traits had statistically significant h²SNP estimates that were also determined to be moderately to highly heritable including: INS‐OST (0.359; s.e. = 0.185), leptin (0.486; s.e. = 0.177), GLU‐OST (0.566 s.e. = 0.175), insulin (0.592; s.e. = 0.195), NEFA (0.684; s.e. = 0.164), and adiponectin (0.913; s.e. = 0.181). MAIN LIMITATIONS: Insufficient population size may have limited power to obtain statistically significant h²SNP estimates for ACTH (both breeds), glucose and triglycerides in Morgans and GLU‐OST in Welsh ponies. CONCLUSIONS: This study provides the first concrete evidence of a genetic contribution to key phenotypes associated with EMS. Eight of these nine traits had moderate to high h²SNP estimates in this cohort. These data demonstrate that continued research for identification of the genetic risk factors for EMS phenotypes within and across breeds is warranted.
-
associations between endocrine disrupting chemicals and Equine Metabolic Syndrome phenotypes
Chemosphere, 2019Co-Authors: S A Durwardakhurst, Nichol Schultz, E M Norton, Aaron Rendahl, Harrie Besselink, Peter A Behnisch, A Brouwer, R J Geor, James R Mickelson, Molly E MccueAbstract:Abstract Equine Metabolic Syndrome (EMS) is characterized by abnormalities in insulin regulation, increased adiposity and laminitis, and has several similarities to human Metabolic Syndrome. A large amount of environmental variability in the EMS phenotype is not explained by commonly measured factors (diet, exercise, and season), suggesting that other environmental factors play a role in EMS development. Endocrine disrupting chemicals (EDCs) are associated with Metabolic Syndrome and other endocrine abnormalities in humans. This led us to hypothesize that EDCs are detectable in horse plasma and play a role in the pathophysiology of EMS. EDCs acting through the aryl hydrocarbon and estrogen receptors, were measured in plasma of 301 horses from 32 farms. The median (range) TEQ (2,3,7,8-TCDD equivalent) and EEQ (17β-estradiol equivalent) were 19.29 pg/g (0.59–536.36) and 10.50 pg/ml (4.35–15000.00), respectively. TEQ was negatively associated with plasma fat extracted and batch analyzed. EEQ was positively associated with pregnancy and batch analyzed, and negatively associated with being male and superfund score ≤100 miles of the farm. Of particular interest, serum glucose and insulin, glucose and insulin post oral sugar challenge, and leptin concentrations were associated with EEQ, and serum triglyceride concentration was associated with TEQ. Overall, we demonstrated that EDCs are present in the plasma of horses and may explain some of the environmental variability in measured EMS phenotypes. This is the first example of EDCs being associated with clinical disease phenotype components in domestic animals.
-
evaluation of an hmga2 variant for pleiotropic effects on height and Metabolic traits in ponies
Journal of Veterinary Internal Medicine, 2019Co-Authors: E M Norton, Nichol Schultz, R J Geor, James R Mickelson, Felipe Avila, Molly E MccueAbstract:Background Ponies are highly susceptible to Metabolic derangements including hyperinsulinemia, insulin resistance, and adiposity. Hypothesis/objectives Genetic loci affecting height in ponies have pleiotropic effects on Metabolic pathways and increase the susceptibility to Equine Metabolic Syndrome (EMS). Animals Two hundred ninety-four Welsh ponies and 529 horses. Methods Retrospective study of horses phenotyped for Metabolic traits. Correlations between height and Metabolic traits were assessed by Pearson's correlation coefficients. Complementary genome-wide analysis methods were used to identify a region of interest (ROI) for height and Metabolic traits, determine the fraction of heritability contributed by the ROI, and identify candidate genes. Results There was an inverse relationship between height and baseline insulin (-0.26) in ponies. Genomic signature of selection and association analyses for both height and insulin identified the same ~1.3 megabase region on chromosome 6 that contained a shared ancestral haplotype between these traits. The ROI contributed ~40% of the heritability for height and ~20% of the heritability for insulin. High-mobility group AT-hook 2 was identified as a candidate gene, and Sanger sequencing detected a c.83G>A (p.G28E) variant associated with height in Shetland ponies. In our cohort of ponies, the A allele had a frequency of 0.76, was strongly correlated with height (-0.75), and was low to moderately correlated with Metabolic traits including: insulin (0.32), insulin after an oral sugar test (0.25), non-esterified fatty acids (0.19), and triglyceride (0.22) concentrations. Conclusions and clinical importance These data have important implications for identifying individuals at risk for EMS.
Lynda Bourebaba - One of the best experts on this subject based on the ideXlab platform.
-
cladophora glomerata methanolic extract promotes chondrogenic gene expression and cartilage phenotype differentiation in Equine adipose derived mesenchymal stromal stem cells affected by Metabolic Syndrome
Stem Cell Research & Therapy, 2019Co-Authors: Krzysztof Marycz, Izabela Michalak, Lynda Bourebaba, Meriem Baouche, Katarzyna KucharczykAbstract:Chondrogenesis represents a highly dynamic cellular process that leads to the establishment of various types of cartilage. However, when stress-related injuries occur, a rapid and efficient regeneration of the tissues is necessary to maintain cartilage integrity. Mesenchymal stem cells (MSCs) are known to exhibit high capacity for self-renewal and pluripotency effects, and thus play a pivotal role in the repair and regeneration of damaged cartilage. On the other hand, the influence of certain pathological conditions such as Metabolic disorders on MSCs can seriously impair their regenerative properties and thus reduce their therapeutic potential. In this investigation, we attempted to improve and potentiate the in vitro chondrogenic ability of adipose-derived mesenchymal stromal stem cells (ASCs) isolated from horses suffering from Metabolic Syndrome. Cultured cells in chondrogenic-inductive medium supplemented with Cladophora glomerata methanolic extract were experimented for expression of the main genes and microRNAs involved in the differentiation process using RT-PCR, for their morphological changes through confocal and scanning electron microscopy and for their physiological homeostasis. The different added concentrations of C. glomerata extract to the basic chondrogenic inductive culture medium promoted the proliferation of Equine Metabolic Syndrome ASCs (ASCsEMS) and resulted in chondrogenic phenotype differentiation and higher mRNA expression of collagen type II, aggrecan, cartilage oligomeric matrix protein, and Sox9 among others. The results reveal an obvious inhibitory effect of hypertrophy and a strong repression of miR-145-5p, miR-146-3p, and miR-34a and miR-449a largely involved in cartilage degradation. Treated cells additionally exhibited significant reduced apoptosis and oxidative stress, as well as promoted viability and mitochondrial potentiation. Chondrogenesis in EqASCsEMS was found to be prominent after chondrogenic induction in conditions containing C. glomerata extract, suggesting that the macroalgae could be considered for the enhancement of ASC cultures and their reparative properties.
-
nortropane alkaloids as pharmacological chaperones in the rescue of Equine adipose derived mesenchymal stromal stem cells affected by Metabolic Syndrome through mitochondrial potentiation endoplasmic reticulum stress mitigation and insulin resistance
Stem Cell Research & Therapy, 2019Co-Authors: Krzysztof Marycz, Lynda Bourebaba, Fatiha Bedjou, Michael RockenAbstract:Equine Metabolic Syndrome (EMS) refers to a cluster of associated abnormalities and Metabolic disorders, including insulin resistance and adiposity. The numerous biological properties of mesenchymal stem cells (MSCs), including self-renewal and multipotency, have been the subject of many in-depth studies, for the management of EMS; however, it has been shown that this cell type may be affected by the condition, impairing thus seriously their therapeutic potential. Therefore, an attempt to rescue EMS adipose-derived stem cells (ASCs) with calystegines (polyhydroxylated alkaloids) that are endowed with strong antioxidant and antidiabetic abilities was performed. ASCs isolated from EMS horses were subsequently treated with various concentrations of total calystegines. Different parameters were then assessed using flow cytometry, confocal as well as SE microscopy, and RT-qPCR. Our results clearly demonstrated that calystegines could improve EqASC viability and proliferation and significantly reduce apoptosis, via improvement of mitochondrial potentiation and functionality, regulation of pro- and anti-apoptotic pathways, and suppression of ER stress. Furthermore, nortropanes positively upregulated GLUT4 and IRS transcripts, indicating a possible sensitizing or mimetic effect to insulin. Most interesting finding in this investigation lies in the modulatory effect of autophagy, a process that allows the maintenance of cellular homeostasis; calystegines acted as pharmacological chaperones to promote cell survival. Obtained data open new perspectives in the development of new drugs, which may improve the Metabolic dynamics of cells challenged by MS.
Nicholas Frank - One of the best experts on this subject based on the ideXlab platform.
-
eceim consensus statement on Equine Metabolic Syndrome
Journal of Veterinary Internal Medicine, 2019Co-Authors: A E Durham, Ellen Roelfsema, Nicholas Frank, C M Mcgowan, N J Menziesgow, Ingrid Vervuert, Karsten Feige, Kerstin FeyAbstract:Equine Metabolic Syndrome (EMS) is a widely recognized collection of risk factors for endocrinopathic laminitis. The most important of these risk factors is insulin dysregulation (ID). Clinicians and horse owners must recognize the presence of these risk factors so that they can be targeted and controlled to reduce the risk of laminitis attacks. Diagnosis of EMS is based partly on the horse's history and clinical examination findings, and partly on laboratory testing. Several choices of test exist which examine different facets of ID and other related Metabolic disturbances. EMS is controlled mainly by dietary strategies and exercise programs that aim to improve insulin regulation and decrease obesity where present. In some cases, pharmacologic aids might be useful. Management of an EMS case is a long-term strategy requiring diligence and discipline by the horse's carer and support and guidance from their veterinarians.
-
comparison of plasma active glucagon like peptide 1 concentrations in normal horses and those with Equine Metabolic Syndrome and in horses placed on a high grain diet
Journal of Equine Veterinary Science, 2016Co-Authors: Kelly A Chameroy, Nicholas Frank, Sarah B Elliott, Raymond C BostonAbstract:Abstract Hyperinsulinemia is associated with laminitis in horses, and active glucagon-like peptide 1 (aGLP-1) stimulates insulin secretion. We hypothesized that plasma aGLP-1 concentrations measured during an oral sugar test (OST) would differ significantly between normal horses and those with Equine Metabolic Syndrome (EMS) and that aGLP-1 concentrations would increase when EMS horses were placed on a high-grain diet. An enzyme-linked immunosorbent assay for aGLP-1 was validated with Equine plasma and six horses with EMS, and 10 healthy Quarter horse crossbred mares were compared. Eleven months later, the same horses with EMS were placed on a high-grain diet for 8 weeks and aGLP-1 concentrations were measured during an oral glucose tolerance test at 0 and 8 weeks. Frequently sampled intravenous glucose tolerance tests were also performed. The assay was validated with Equine plasma and concentrations increased during the OST. Area under the aGLP-1 curve did not differ between normal and EMS horses. There was a weak trend ( P = .097) toward a higher maximum percentage increase in aGLP-1 concentrations during the OST in EMS horses compared with normal horses. Body weight increased ( P = .031) after 8 weeks when EMS horses were placed on a high-grain diet. Resting (fasted) insulin concentrations significantly increased ( P = .012), but plasma aGLP-1 concentrations did not change significantly. Our hypotheses were not supported because plasma aGLP-1 concentrations did not differ significantly between normal horses and those with EMS and did not increase when EMS horses were placed on a high-grain diet for 8 weeks. However, a trend toward higher percentage increases in aGLP-1 concentrations during the OST was detected in EMS horses, compared with normal horses, and this warrants further investigation.
-
effect of age season body condition and endocrine status on serum free cortisol fraction and insulin concentration in horses
Journal of Veterinary Internal Medicine, 2016Co-Authors: Kelsey A Hart, Dianne Mcfarlane, D M Wochele, Natalie Norton, Anne A Wooldridge, Nicholas FrankAbstract:Background Increased free cortisol fraction is associated with insulin dysregulation (ID) in people with Metabolic Syndrome and Cushing's Disease. Free cortisol has not been investigated in Equine endocrine disorders. Hypotheses (1) In healthy horses, sex, age, body condition score (BCS), and season impact free cortisol; (2) free cortisol is increased in horses with Pituitary Pars Intermedia Dysfunction (PPID) or Equine Metabolic Syndrome (EMS). Animals Fifty-seven healthy horses; 40 horses and ponies with PPID (n = 20) or EMS (n = 20). Methods Prospective study. Serum collected seasonally from healthy animals and archived serum from PPID and EMS animals was analyzed for insulin, total and free cortisol concentrations, and free cortisol fraction (FCF). Linear mixed models were used to determine effects of age, sex, season, and BCS on hormones in controls. Hormone measurements were compared between disease groups and age- and season-matched controls with t-tests. EMS and hyperinsulinemic PPID animals were combined in an ID (hyperinsulinemia) group. Results Free cortisol concentrations were increased in overweight/obese controls (0.3 ± 0.1 μg/dL) compared to lean controls (0.2 ± 0.1 μg/dL; P = .017). Mean FCF was significantly higher in animals with PPID (8.8 ± 5.8 μg/dL, P = .005) or ID (8.8 ± 10.2 μg/dL, P = .039) than controls (5.0 ± 0.9 μg/dL), but total cortisol concentrations were similar (P ≥ .350) (PPID: 4.2 ± 4.3 μg/dL; ID: 5.0 ± 4.5 μg/dL; controls: 4.6 ± 1.7 and 5.1 ± 2.1 μg/dL). Conclusions and Clinical Importance Increased FCF is associated with obesity in healthy horses and with ID (hyperinsulinemia) in horses and ponies with endocrine disease. Decreased plasma cortisol-binding capacity could be a component of these endocrine disorders in horses.
-
effects of Equine Metabolic Syndrome on inflammatory responses of horses to intravenous lipopolysaccharide infusion
American Journal of Veterinary Research, 2013Co-Authors: Elizabeth M. Tadros, Nicholas Frank, Robert L DonnellAbstract:Objective—To test the hypothesis that inflammatory responses to endotoxemia differ between healthy horses and horses with Equine Metabolic Syndrome (EMS). Animals—6 healthy horses and 6 horses with EMS. Procedures—Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline data were obtained 30 minutes before each infusion. After infusion, a physical examination was performed hourly for 9 hours and at 15 and 21 hours; a whole blood sample was collected at 30, 60, 90, 120, 180, and 240 minutes for assessment of inflammatory cytokine gene expression. Liver biopsy was performed between 240 and 360 minutes after infusion. Results—Following lipopolysaccharide infusion in healthy horses and horses with EMS, mean rectal temperature, heart rate, and respiratory rate increased, compared with baseline findings, as did whole blood gene expression of interleukin...
-
effects of intravenous lipopolysaccharide infusion on glucose and insulin dynamics in horses with Equine Metabolic Syndrome
American Journal of Veterinary Research, 2013Co-Authors: Elizabeth M. Tadros, Nicholas Frank, Fiamma Gomez De Witte, Raymond C BostonAbstract:Objective—To test the hypothesis that glucose and insulin dynamics during endotoxemia differ between healthy horses and horses with Equine Metabolic Syndrome (EMS). Animals—6 healthy adult mares and 6 horses with EMS. Procedures—Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline insulin-modified frequently sampled IV glucose tolerance tests were performed 27 hours before and then repeated at 0.5 and 21 hours after infusion. Results were assessed via minimal model analysis and area under the curve values for plasma glucose and serum insulin concentrations. Results—Lipopolysaccharide infusion decreased insulin sensitivity and increased area under the serum insulin concentration curve (treatment × time) in both healthy and EMS-affected horses, compared with findings following saline solution administration. The magnitude of increase in area und...