1-Deoxynojirimycin containing Morus alba leaf-based food modulates the gut microbiome and expression of genes related to obesity.

BACKGROUND: Obesity is a serious disease with an alarmingly high incidence that can lead to other complications in both humans and dogs. Similar to humans, obesity can cause metabolic diseases such as diabetes in dogs. Natural products may be the preferred intervention for metabolic diseases such as obesity. The compound 1-deoxynojirimycin, present in Morus leaves and other sources has antiobesity effects. The possible antiobesity effect of 1-deoxynojirimycin containing Morus alba leaf-based food was studied in healthy companion dogs (n = 46) visiting the veterinary clinic without a history of diseases. Body weight, body condition score (BCS), blood-related parameters, and other vital parameters of the dogs were studied. Whole-transcriptome of blood and gut microbiome analysis was also carried out to investigate the possible mechanisms of action and role of changes in the gut microbiome due to treatment. RESULTS: After 90 days of treatment, a significant antiobesity effect of the treatment food was observed through the reduction of weight, BCS, and blood-related parameters. A whole-transcriptome study revealed differentially expressed target genes important in obesity and diabetes-related pathways such as MLXIPL, CREB3L1, EGR1, ACTA2, SERPINE1, NOTCH3, and CXCL8. Gut microbiome analysis also revealed a significant difference in alpha and beta-diversity parameters in the treatment group. Similarly, the microbiota known for their health-promoting effects such as Lactobacillus ruminis, and Weissella hellenica were abundant (increased) in the treatment group. The predicted functional pathways related to obesity were also differentially abundant between groups. CONCLUSIONS: 1-Deoxynojirimycin-containing treatment food have been shown to significantly improve obesity. The identified genes, pathways, and gut microbiome-related results may be pursued in further studies to develop 1-deoxynojirimycin-based products as candidates against obesity.

The role of endoplasmic reticulum stress in metabolic diseases and mammary epithelial cell homeostasis in dairy cows.

High-yielding dairy cows undergo various physiological stresses during the transitional phase of the calving cycle. In this period, they experience negative energy balance, subjecting the liver to significant metabolic stress from an influx of nonesterified fatty acids. This metabolic stress not only impairs liver function but also diminishes milk production. Early lactation dairy cows may develop endoplasmic reticulum (ER) stress in the liver, potentially leading to liver-related diseases and contributing to ER stress in mammary epithelial cells, resulting in decreased milk production. Natural products that alleviate ER stress have been identified, and if further in vivo studies confirm their efficacy, they have potential as feed additives to prevent disease and reduce milk yield. Conversely, physiological levels of ER stress play a role in mammary gland development and positively influence protein synthesis in milk. Understanding the threshold level of ER stress in mammary tissue and its detailed mechanisms will be crucial in dairy farming.

Synergistic anti-infectious bronchitis virus activity of Phillygenin combined Baicalin by modulating respiratory microbiota and improving metabolic disorders.

Phillygenin (PHI) and Baicalin (Bai) are the major chemical ingredients extracted from Forsythia suspensa and Scutellaria baicalensis, respectively. The mixture of Forsythia suspensa and Scutellaria baicalensis according to the theories of Traditional Chinese Veterinary Medicine, compounded formulation can effectively exert heat-clearing and detoxifying effect, but the synergistic anti-IBV activity of PHI combined with Bai was unclear. Here, the protection of PHI combined with Bai on avian infectious bronchitis virus (IBV) M41 infection and the change of respiratory microbiota and metabolomics profiles in broilers that infected with IBV were investigated. According to the experimental findings, the combination of PHI and Bai effectively alleviated broilers' slowing-growth weight and respiratory symptoms. This was accompanied by a reduction in viral copies and histopathological changes, as well as an increase of antiviral protein (G3BP1) level in tracheas and anti-IBV antibody levels in serum. In addition, 16s RNA sequencing revealed that IBV infection significantly changed respiratory microbiota composition at different taxonomic levels and respiratory metabolism composition in broilers. Interestingly, PHI combined with Bai modulated the composition of respiratory microfloras, especially the abundance of Firmicutes and Lactobacillaceae were upregulated, as well as the abundance of Proteobacteria was downregulated. The metabolomics results indicated that PHI combined with Bai involved in glucose, lipids, amino acids and nucleotide metabolism during IBV infection. In summary, PHI combined with Bai exhibited a synergistic effect on preventing infectious bronchitis (IB), with the protection being closely associated with the composition of respiratory microbiota and metabolites. Therefore, adding the mixture of PHI and Bai to the chicken drinking water is recommended to prevent and control IB in clinical.

A missense variant in DGKG as a recessive functional variant for hepatic fibrinogen storage disease in Wagyu cattle.

Hepatic fibrinogen storage disease (HFSD) was diagnosed in a 5-month-old Wagyu calf with a history of recurrent respiratory disease. It was characterized by lethargy, dehydration, acidemia, and increased liver enzyme activities. Histologically, disseminated hepatocytes were swollen and showed a single, sharply demarcated, faintly eosinophilic cytoplasmic inclusion with a ground-glass appearance, with the nucleus in an eccentric position. Cytoplasmic inclusions did not stain with the periodic acid-Schiff (PAS) reaction. Using a rabbit polyclonal antibody against fibrinogen, the cytoplasmic vacuoles in the hepatocytes stained intensely. Electron microscopy disclosed hepatocytes with membrane-bound cytoplasmic inclusions filled with fine granular material interspersed with a few coarse-grained electron-dense granules. A trio whole-genome sequencing approach identified a deleterious homozygous missense variant in DGKG (p.Thr721Ile). The allele frequency in 209 genotyped Wagyu was 7.2%. This is a report of a DGKG-related recessive inherited disorder in cattle and adds DGKG to the list of candidate genes for HFSD in other species.

Relationship between periparturient diseases, metabolic markers and the dynamics of hair cortisol concentrations in dairy cows.

Hair cortisol concentration (HCC) might represent a promising marker for retrospective welfare assessment of dairy cows. The objective of the study was to explore the dynamics of HCC in diseased and healthy cows from eight-week ante partum (AP) to eight-week post partum (PP). Twenty-four pregnant cows were followed from drying off to week eight PP. Tail hair was used to measure cortisol at five different time points. The occurrence of peripartum diseases, lameness and the body condition score (BCS) were monitored on a weekly basis. Blood ß-hydroxybutyric acid, non-esterified fatty acids, calcium and insulin-like growth factor-1 (IGF-1) concentrations were measured. The temperature-humidity index (THI) was continuously recorded. The median values of HCC in all cows were 0.4, 0.3, 0.6, 0.8 and 0.5 pg/mg at weeks eight, four AP, calving, weeks four, eight PP, respectively. There was no association between HCC and the occurrence of peripartum diseases (P ≥ 0.05). A positive correlation between HCC and BCS loss (P < 0.01) and THI (P < 0.05) was observed. The occurrence of peripartum diseases was associated with low IGF-1 during the study period but no relationship was found between cortisol and IGF-1 levels (P ≥ 0.05). Brown Swiss cows showed higher HCC (P < 0.01) at weeks eight, four AP, and week four PP and lower average milk yield (P < 0.05) than Holstein-Friesian cows. In conclusion, HCC was not a suitable marker for peripartum diseases but it could reflect a stress response, which is linked to BCS loss, heat stress and breed.

Ruminant Metabolic Diseases: Perturbed Homeorhesis.

The 6-week period encompassing parturition, termed the transition period, is recognized as the most fragile period in the life cycle of the ruminant animal. The period accounts for the greatest risk of health events that can adversely affect animal health, lactational performance, and future reproductive success. Critical endocrine and metabolic adaptations take place in allowing the animal to change nutrient priorities from supporting pregnancy to sustaining lactation. A reductionist perspective of underlying pathogenesis provided minimal metabolic disease prevalence improvement. Recent research has recognized metabolic regulatory complexity and role for activated inflammatory response underpinning dysregulation of homeorhesis during transition.

Metabolic Diseases in Beef Cattle.

Beef cattle are less prone to metabolic diseases as compared with dairy cattle; however, there are disease entities of concern in feedlot and cow-calf beef cattle operations. In one study, a prevalence of 2% was found for ruminant acidosis in a feedlot; however, there is little prevalence information published with regard to metabolic diseases in beef cattle.1 Metabolic diseases covered in this article are hypomagnesemia, ruminal acidosis, and all of the common sequelae, polioencephalomalacia, manganese deficiency, and protein-energy malnutrition (PEM).

Profound Perturbation in the Metabolome of a Canine Obesity and Metabolic Disorder Model.

Canine models are increasingly being used in metabolic studies due to their physiological similarity with humans. The present study aimed to identify changes in metabolic pathways and biomarkers with potential clinical utility in a canine model of obesity and metabolic disorders induced by a high-fat diet (HFD). Eighteen male beagles were included in this study, 9 of which were fed a HFD for 24 weeks, and the remaining 9 were fed normal chow (NC) during the same period. Plasma and urine samples were collected at weeks 12 and 24 for untargeted metabolomic analysis. Dogs fed a HFD showed a gradual body weight increase during the feeding period and had hyperlipidemia, increased leukocyte counts, and impaired insulin sensitivity at week 24. Plasma and urine metabonomics analysis displayed clear separations between the HFD-fed and NC-fed dogs. A total of 263 plasma metabolites varied between the two groups, including stearidonic acid, linolenic acid, carnitine, long-chain ceramide, 3-methylxanthine, and theophylline, which are mainly engaged in fatty acid metabolism, sphingolipid metabolism, and caffeine metabolism. A total of 132 urine metabolites related to HFD-induced obesity and metabolic disorders were identified, including 3-methylxanthine, theophylline, pyridoxal 5'-phosphate, and harmine, which participate in pathways such as caffeine metabolism and vitamin digestion and absorption. Eight metabolites with increased abundance (e.g., 3-methylxanthine, theophylline, and harmine) and 4 metabolites with decreased abundance (e.g., trigonelline) in both the plasma and urine of the HFD-fed dogs were identified. In conclusion, the metabolomic analysis revealed molecular events underlying a canine HFD model and identified several metabolites as potential targets for the prevention and treatment of obesity-related metabolic disorders.

Supplementation of omega-3 and dietary factors can influence the cholesterolemia and triglyceridemia in hyperlipidemic Schnauzer dogs: A preliminary report.

Primary hyperlipidaemia in Schnauzer is characterized by increased plasma triglycerides (TG) and/or total cholesterol (TC) concentration and is associated with an increased risk of developing pancreatitis, insulin resistance and seizures. In humans, omega-3 fatty acids in addition to a low-fat diet can be used to reduce TG and TC. This study evaluated the therapeutic efficacy of omega-3 fatty acids associated to a diet management with two different fat content in Schnauzer with primary hyperlipidaemia. Eighteen dogs with primary hyperlipidaemia were divided into two groups: group 1, n = 10, 8 females, 2 males, age (mean ± standard deviation) of 7.13 ± 2.70 years and body weight (BW) (mean ± standard deviation) of 7.25 ± 1.22 kg were treated with fish oil (approximately 730 mg/day of omega-3) associated with a low-fat and low-calorie diet (approximately 24g of fat/1000 kcal) for 90 days (T90); and group 2, n = 8 dogs, 6 females, 2 males, with 7.0 ± 1.77 years old and average BW of 8.36 ± 1.51 kg, treated with fish oil (approximately 730 mg/day of omega-3) and maintenance diet with moderate amount of fat (approximately 33g of fat/1000 kcal) for 90 days. Plasma TG and TC concentrations and lipoprotein (LP) profile (VLDL, LDL, HDL) were evaluated before and after treatment. TG and TC serum concentrations, expressed in mg/dL (mean ± standard deviation), before and after treatment in group 1 were: TG = 391.30 ± 487.86 (T0) and 118.7 ± 135.21 (T90); TC = 308.2 ± 63.06 (T0) and 139 ± 36.91 (T90). As for group 2, TG = 391.63 ± 336.89 (T0) and 250.75 ± 211.56 (T90); TC = 257.25 ± 92.88 (T0) and 207.25 ± 63.79 (T90). A reduction (p<0.05) of TG and TC was observed in both groups. The distribution of TG and TC among LP was not different between the pre (T0) and post treatment (T90) periods. After 90 days of treatment, the administration of omega-3 fatty acids, associated with a low-fat or maintenance diet reduced triglyceridemia and cholesterolemia without altering LP profile. The current investigation shows that both therapies were effective in reducing plasma TC and TG concentrations without altering LP profile.

Thiamine ameliorates metabolic disorders induced by a long-term high-concentrate diet and promotes rumen epithelial development in goats.

Data indicate that dietary thiamine supplementation can partly alleviate rumen epithelium inflammation and barrier function in goats fed a high-concentrate diet. The current work aimed to explore whether thiamine promotes rumen epithelium development by regulating carbohydrate metabolism during a long period of feeding high levels of concentrate. For the experiment, 24 female Boer goats (35.62 ± 2.4 kg of body weight) in parity 1 or 2 were allocated to 3 groups (8 goats per replicate) receiving a low-concentrate diet (concentrate:forage 30:70), a high-concentrate diet (HC; concentrate:forage 70:30), or a high-concentrate diet (concentrate:forage 70:30) supplemented with 200 mg of thiamine/kg of dry matter intake (HCT; concentrate:forage 70:30). On the last day of 12 wk, rumen fluid and blood samples were collected to measure ruminal parameters, endotoxin lipopolysaccharide, and blood inflammatory cytokines. Goats were slaughtered to collect ruminal tissue to determine differential metabolites, enzyme activities, and gene expression. Liquid chromatography-tandem mass spectrometry analysis revealed that the HCT group had significantly increased concentrations of d-glucose 6-phosphate, d-fructose 6-phosphate, glyceraldehyde 3-phosphate, thiamine pyrophosphate, oxaloacetate, acetyl-CoA, succinyl-CoA, sedoheptulose 7-phosphate, ribose 5-phosphate, and NADPH compared with the HC group. The pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase enzyme activities in the rumen epithelium of the HCT group were higher than those in the HC group. The plasma total antioxidant capacity values for the HCT group were greater than those for the HC group. The rumen epithelium ATP content in the HCT group was higher than that in the HC group. Compared with the HCT group, the HC group had a lower mRNA abundance of CCND1, CCNA2, CDK2, CDK4, CDK6, BCL2, PI3K, and AKT1. Taken together, the results suggest that dietary thiamine supplementation could ameliorate disorders in the tricarboxylic acid cycle and the pentose phosphate pathway induced by a long-term high-concentrate diet and could promote rumen epithelial growth.

Perturbations of the hepatic proteome behind the onset of metabolic disorders in mouse offspring developed following embryo manipulation.

Assisted Reproductive Technologies (ART) allowed the births of >8 million babies worldwide. Even if ART children are healthy at birth, several studies reported that ART may cause changes in foetal programming, leading to an increased predisposition to metabolic disorders in adulthood. Previous studies on mouse model showed obesity, glucose intolerance, and hepatic lipid accumulation in ART offspring. A cumulative effect of the different components of ART protocol has been previously described, for example, in the occurrence of epigenetic defects. Here, we investigated whether there is a cumulative effect of embryo transfer (ET), in vitro culture (IVC) and blastomere biopsy (BB) in the onset of metabolic disorders in mouse offspring vs those naturally conceived (Control - CTR). To this aim, proteomic analysis was performed on the livers from adult mouse offspring developed following ET, IVC and BB vs CTR. We observed deregulated expression of proteins involved in lipid, carbohydrate, energy metabolisms and cellular processes in ART offspring. Moreover, we found increased body weight in all ART offspring while i) insulin resistance in BB male, ii) females glucose intolerance and high level of triglycerides and cholesterol in BB females and iii) low levels of interleukin-6 in BB, IVC and ET males. In conclusion, our study suggests that the use of various embryo manipulations influences the metabolic health of adult offspring, resulting in an increased predisposition to hepatic diseases and metabolic syndrome in a sex-specific manner.

Milk yield and composition in dairy cows with post-partum disorders / [Produção e composição do leite em vacas com desordens no pós-parto]

This study aimed to determine the impact of different post-partum disorders on milk yield and composition. One hundred and fifteen Holstein cows from a commercial dairy farm located in the state of Rio Grande do Sul in southern Brazil were monitored up to 62 days post-partum. During this period, body condition score evaluation and animal clinical examination were conducted. Percentages of fat, protein, and lactose, as well as somatic cells score, were determined in milk samples. The AST activity and concentrations of NEFA, calcium, and BHBA, were analyzed in blood samples. The occurrence of clinical disorders was identified in 30 (26%) cows. Subclinical disorders were identified in 64 (56%) cows. Only 21 (18%) cows did not suffer any kind of disorder within the studied period. In this study, no significant differences were found in milk production, protein, and somatic cell count in clinical, subclinical, and healthy cows. Milk fat and the fat: protein quotient (F:P) were higher in cows with clinical disorders and the 6 to 21 days in milk, and lactose were lower in cows with clinical disorders and the 22 to 42 days in milk (P<0.05).(AU)

O objetivo deste estudo foi determinar o impacto de diferentes distúrbios após o parto na produção de leite e em sua composição. Cento e quinze vacas Holandesas de uma fazenda de gado leiteiro, localizada em estado da região Sul do Brasil, foram monitoradas até 62 dias após o parto. Durante esse período, foram realizadas avaliações do escore de condição corporal e exame clínico nos animais. As porcentagens de gordura, proteína e lactose, bem como o escore de células somáticas, foram determinadas nas amostras de leite. A atividade do AST e as concentrações de NEFA, cálcio e BHBA foram analisadas em amostras de sangue. A ocorrência de distúrbios clínicos foi identificada em 30 (26%) vacas, os distúrbios subclínicos foram identificados em 64 (56%) vacas. Apenas 21 (18%) vacas não sofreram nenhum tipo de distúrbio ao longo do período estudado. Neste estudo, não foram encontradas diferenças significativas na produção do leite, proteína e na contagem de células somáticas em vacas com doenças clínicas, subclínicas e saudáveis. No leite, a gordura e o quociente gordura e proteína (G:P) foram maiores em vacas com doença clínica no período de seis a 21 dias de lactação, e a lactose foi menor em vacas com doença clínica no período de 22 a 42 dias de lactação (P<0,05).(AU)

Buriti pulp oil did not improve high-fat diet-induced metabolic disorders in c57bl/6 mice.

Metabolic syndrome (MetS) and obesity are growing in many parts of the world, becoming public health problems. It is proposed that foods with functional properties can assist in the treatment of these diseases. Crude buriti pulp oil (BPO) is a food traditionally consumed by residents in the Pantanal, Cerrado and Brazilian Amazon. It is rich in oleic acid, tocopherols and carotenoids, emerging as a potential functional food. Thus, this study aimed to evaluate the effect of the supplementation of BPO on metabolic disorders caused by a high-fat diet. Four groups of C57BL6 mice were used, a lean group with AIN-93M diet and control oil supplementation, an obese group with a high-fat diet and control oil supplementation, and two obese groups with a high-fat diet and BPO supplementation in the amounts of 50 and 100 mg/kg. BPO worsened the metabolic state caused by the high-fat diet, worsening risk factors associated with MetS, as the abdominal circumference and retroperitoneal fat, serum levels of total cholesterol, uric acid, alanine transaminase, glucose and triglycerides, and renal fat, in addition to changes in glycaemic control and oxidative stress markers. C57BL/6 mice fed with a high-fat diet and supplemented with BPO presented a worsening in metabolic risk factors associated with MetS.

The Genetic Basis of Obesity and Related Metabolic Diseases in Humans and Companion Animals.

Obesity is one of the most prevalent health conditions in humans and companion animals globally. It is associated with premature mortality, metabolic dysfunction, and multiple health conditions across species. Obesity is, therefore, of importance in the fields of medicine and veterinary medicine. The regulation of adiposity is a homeostatic process vulnerable to disruption by a multitude of genetic and environmental factors. It is well established that the heritability of obesity is high in humans and laboratory animals, with ample evidence that the same is true in companion animals. In this review, we provide an overview of how genes link to obesity in humans, drawing on a wealth of information from laboratory animal models, and summarise the mechanisms by which obesity causes related disease. Throughout, we focus on how large-scale human studies and niche investigations of rare mutations in severely affected patients have improved our understanding of obesity biology and can inform our ability to interpret results of animal studies. For dogs, cats, and horses, we compare the similarities in obesity pathophysiology to humans and review the genetic studies that have been previously reported in those species. Finally, we discuss how veterinary genetics may learn from humans about studying precise, nuanced phenotypes and implementing large-scale studies, but also how veterinary studies may be able to look past clinical findings to mechanistic ones and demonstrate translational benefits to human research.

Epidemiological study to investigate the incidence and prevalence of clinical mastitis, peracute mastitis, metabolic disorders and peripartum disorders, on a dairy farm in a temperate zone in Japan.

BACKGROUND: Our aim was to investigate the incidence and prevalence of clinical mastitis, peracute mastitis, metabolic disorders, and peripartum disorders, and to examine factors affecting the prevalence of each disease in cows raised on a large dairy farm in a temperate climate in Japan. The present study was performed on a large commercial dairy farm with approximately 2500 Holstein cows. Data were collected from 2014 to 2018, and involved 9663 calving records for 4256 cows. RESULTS: The incidence rate on the farm was 21.9% for clinical mastitis, 10.4% for peracute mastitis, 2.9% for metabolic disorders, and 3.2% for peripartum disorders. The prevalence rates for clinical mastitis, peracute mastitis, metabolic disorders, and peripartum disorders were 28.0, 13.3, 3.7, and 4.0%, respectively. In all four diseases, the probability of time to occurrence for each disease was associated with parity and calving season (P < 0.05). Regarding metabolic disorders and peripartum disorders, the probability of occurrence decreased during the first 10 days after calving. CONCLUSIONS: Our results showed that clinical mastitis occurred most often in this temperate zone, and that metabolic disorders and peripartum disorders occurred from calving to day 10 post-calving.

Prognostic value of serum potassium level predicting the duration of recumbency in downer cows due to metabolic disorders.

Downer cows and variations in the treatment response are of great interest to farmers. Positively responded animals get up at different extended periods after receiving the same treatment protocol. The objective of this study is to determine if there is any association between the duration of recumbency and the level of serum biomarkers. Serum samples from 165 crossbred Holstein dairy cows (105 downer cows of metabolic causes only and 50 healthy) and from 65 cured cows after treatment were used for analysis of calcium (Ca), inorganic phosphorus (P), potassium (K), magnesium (Mg), creatine phosphokinase (CPK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), beta-hydroxybutyric acid (BHBA), non-esterified fatty acid (NEFA), and triglycerides (TG). Assessment of diagnostic performance of these biomarkers was performed using analysis of the receiver operating characteristic (ROC). Serum levels of Ca, P, K, and TG decreased significantly (P < 0.001), while CPK, AST, ALT, BHBA, and NEFA increased significantly (P < 0.001) in those downers compared with controls. They achieved high diagnostic performance in ROC curve analysis. Interestingly, 65 cows responded after treatment and stood up (cured cases) after a period of recumbency varying from 4 to 15 days and statistics revealed a significant association (P < 0.05) between those days of recumbency and only serum K levels. We concluded that only the serum potassium (K) level is a significant predictor of post-treatment recumbency period and that the serum P, CPK, and NEFA levels have the highest diagnostic performance.

Evaluation of biochemical profile of dairy cows with metabolic diseases in tropical conditions.

The aims of this study were to characterize the biochemical profile, the reproductive performance and to identify potential predictive biomarkers of disease state of dairy cows with hyperketonemia, lipomobilization and hypocalcemia raised in tropical conditions in southeastern Brazil. Dairy cows (n = 50) were divided into a group of healthy cows (n = 14), cows with lipomobilization (n = 14), cows with hypocalcemia (n = 11), and a group of cows with hyperketonemia (n = 11). Evaluation of body condition score (BCS), body weight (BW) and blood samples was performed on 21, 14, 7, 4 and 2 days before calving, parturition, 1, 7, 14, 21, 30, 45 and 60 days post-partum and milk production was recorded on days 7, 14, 21, 30, 45 and 60 after parturition. Blood samples were assayed for aspartate aminotransferase (AST), gamma-glutammyltransferase (GGT), albumin, total protein, globulin, fibrinogen, total cholesterol, triglyceride, urea and creatinine concentrations. The biochemical profile, BCS, BW, milk production and reproductive performance differed (p < .05) among the groups. Our findings indicate changes in the biochemical profile of dairy cows with metabolic diseases and impaired production and fertility of dairy cows in this group. Variable importance in projection plots demonstrated that cholesterol, urea, total protein, albumin and fibrinogen in the serum were the strongest discriminators between cows with hypocalcemia and healthy cows; and AST, cholesterol, urea and triglycerides for cows with hyperketonemia and healthy cows; and cholesterol, urea, triglycerides, total protein and fibrinogen for lipomobilization and healthy cows, which might be useful as predictive biomarkers of the disease state.

Genetics of Equine Endocrine and Metabolic Disease.

A role for a genetic contribution to equine metabolic syndrome (EMS) and pars pituitary intermedia dysfunction (PPID) has been hypothesized. Heritability estimates of EMS biochemical measurements were consistent with moderately to highly heritable traits. Further, genome-wide association analyses have identified hundreds of regions of the genome contributing to EMS and candidate variants have been identified. The genetics of PPID has not yet been proven. Continued research for the specific genetic risk factors for both EMS and PPID is crucial for gaining a better understanding of the pathophysiology of both conditions and allowing development of genetic tests.

Long-Term Survival of Transplanted Autologous Canine Liver Organoids in a COMMD1-Deficient Dog Model of Metabolic Liver Disease.

The shortage of liver organ donors is increasing and the need for viable alternatives is urgent. Liver cell (hepatocyte) transplantation may be a less invasive treatment compared with liver transplantation. Unfortunately, hepatocytes cannot be expanded in vitro, and allogenic cell transplantation requires long-term immunosuppression. Organoid-derived adult liver stem cells can be cultured indefinitely to create sufficient cell numbers for transplantation, and they are amenable to gene correction. This study provides preclinical proof of concept of the potential of cell transplantation in a large animal model of inherited copper toxicosis, such as Wilson's disease, a Mendelian disorder that causes toxic copper accumulation in the liver. Hepatic progenitors from five COMMD1-deficient dogs were isolated and cultured using the 3D organoid culture system. After genetic restoration of COMMD1 expression, the organoid-derived hepatocyte-like cells were safely delivered as repeated autologous transplantations via the portal vein. Although engraftment and repopulation percentages were low, the cells survived in the liver for up to two years post-transplantation. The low engraftment was in line with a lack of functional recovery regarding copper excretion. This preclinical study confirms the survival of genetically corrected autologous organoid-derived hepatocyte-like cells in vivo and warrants further optimization of organoid engraftment and functional recovery in a large animal model of human liver disease.

Serum acylcarnitine profile in endurance horses with and without metabolic dysfunction.

Mitochondrial ß-oxidation is essential in fat metabolism and can be monitored with blood acylcarnitine profiling, as partly degraded fatty acids accumulate as their carnitine esters. To guarantee continuous energy supply during long-distance exercise, endurance horses oxidise considerable amounts of fat in the mitochondrion. In endurance races over 80 km, glycogen depletion is evident in equine slow-twitch high oxidative muscle fibres and as a consequence, horses participating in endurance races over 80 km rely almost entirely on ß-oxidation of fatty acids. This study investigated mitochondrial fatty acid ß-oxidation in endurance horses exposed to long-distance exercise. Electrospray tandem mass spectrometry analysis of serum acylcarnitine profiles from 10 Arab horses was performed before and after a 160 km endurance race. Results were analysed statistically using ANOVA. Mean speed over the entire race in finishing horses was 16.7 ± 1.2 km/h. Endurance exercise increased mitochondrial ß-oxidation approximately eight-fold (pre-race, 5648.62 ± 1508.52 nmol/L; post-race, 44,243.17 ± 11,504.45 nmol/L; P = 0.001). In these horses, there was an approximately 17-fold increased lipolysis, as demonstrated by elevated serum concentrations of non-esterified fatty acids (NEFA; pre-race, 0.08 ± 0.08 mmol/L; post-race, 1.32 ± 0.36 mmol/L; P < 0.001). In comparison, four Arab horses with poor performance showed an approximately five-fold increase in mitochondrial ß-oxidation (pre-race, 5286.17 ± 3355.16 nmol/L; post-race, 26,660.57 ± 10,064.27 nmol/L; P = 0.009); there was a 29-fold increase in NEFA (pre-race, 0.02 ± 0.01 mmol/L; post-race, 0.58 ± 0.07 mmol/L; P = 0.006) in these horses. Similar post-exercise free carnitine:acetylcarnitine ratios in both groups suggest that the availability of carnitine in long-distance endurance horses might limit performance.