Obese Horses Research Articles

Carbonyl reductase 1 catalyzes 20\u03b2-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity

Carbonyl Reductase 1 (CBR1) is a ubiquitously expressed cytosolic enzyme important in exogenous drug metabolism but the physiological function of which is unknown. Here, we describe a role for CBR1 in metabolism of glucocorticoids. CBR1 catalyzes the NADPH- dependent production of 20β-dihydrocortisol (20β-DHF) from cortisol. CBR1 provides the major route of cortisol metabolism in horses and is up-regulated in adipose tissue in obesity in horses, humans and mice. We demonstrate that 20β-DHF is a weak endogenous agonist of the human glucocorticoid receptor (GR). Pharmacological inhibition of CBR1 in diet-induced obesity in mice results in more marked glucose intolerance with evidence for enhanced hepatic GR signaling. These findings suggest that CBR1 generating 20β-dihydrocortisol is a novel pathway modulating GR activation and providing enzymatic protection against excessive GR activation in obesity.

The equine glucose-dependent insulinotropic polypeptide receptor: A potential therapeutic target for insulin dysregulation.

Metabolic disease is a significant problem that causes a range of species-specific comorbidities. Recently, a better understanding of glucose-dependent insulinotropic polypeptide (GIP) biology has led to the suggestion that inhibiting its action may attenuate obesity in several species. In horses, antagonism of GIP may also reduce hyperinsulinemia, which leads to insulin-associated laminitis, a painful comorbidity unique to this species. However, little is known about GIP in horses. The aims of this study were to examine the tissue distribution of equine GIP receptors (eGIPR), to determine whether eGIPR can be blocked using a GIP antagonist not tested previously in horses, and to establish whether there is any association between GIP concentrations and body mass in this species. Archived tissues from healthy horses were used to establish that eGIPR gene expression was strong in pancreas, heart, liver, kidney, and duodenum and absent in gluteal muscle. Pancreatic islets were isolated from fresh horse pancreas using collagenase digestion and layering through a density gradient. Islet viability was confirmed microscopically and by demonstrating that insulin production was stimulated by glucose in a concentration-dependent manner. Insulin release was also shown to be concentration-dependent with GIP up to 0.1µM, and the response to GIP was decreased ( = 0.037) by the antagonist (Pro3)GIP. As for the relationship between body mass and GIP in vivo postprandial GIP concentrations in archived plasma samples were positively correlated with body condition and cresty neck scores ( < 0.05). Thus, the eGIPR is a potential therapeutic target for insulin dysregulation and obesity in horses.

Time budgets of lean and obese horses kept in individual partially covered pens

Time budgets of lean and obese horses kept in individual partially covered pens

Daily caloric expenditure as estimated by heart rate in lean and obese horses

Daily caloric expenditure as estimated by heart rate in lean and obese horses

Prevalence and management of obese ponies and horses in Maryland

Prevalence and management of obese ponies and horses in Maryland

Genomewide association study reveals a risk locus for equine metabolic syndrome in the Arabian horse.

Equine obesity can cause life-threatening secondary chronic conditions, similar to those in humans and other animal species. Equine metabolic syndrome (EMS), primarily characterized by hyperinsulinemia, is often present in obese horses and ponies. Due to clinical similarities to conditions such as pituitary pars intermedia dysfunction (formerly equine Cushing's disease), conclusive diagnosis of EMS often proves challenging. Aside from changes in diet and exercise, few targeted treatments are available for EMS, emphasizing the need for early identification of at-risk individuals to enable implementation of preventative measures. A genomewide association study (GWAS) using Arabian horses with a history of severe laminitis secondary to EMS revealed significant genetic markers near a single candidate gene () that may play a role in cholesterol homeostasis. The best marker, BIEC2-263524 (chr14:69276814 T > C), was correlated with elevated insulin values and increased frequency of laminitis ( = 0.0024 and = 9.663 × 10, respectively). In a second population of Arabian horses, the BIEC2-263524 marker maintained its associations with higher modified insulin-to-glucose ratio (MIRG) values ( = 0.0056) and BCS ( = 0.0063). Screening of the predicted coding regions by sequencing identified a polymorphic guanine homopolymer and 5 haplotypes in the 3' untranslated region (UTR). An 11 guanine (11-G) allele at was correlated with elevated insulin values in the GWAS population ( = 0.0008) and, in the second population, elevated MIRG and increased BCS > 6.5 ( = 0.0055 and = 0.0162, respectively). The BIEC2-263524-C and the 3' UTR -11(G) polymorphisms were correlated at a 98% frequency, indicating strong linkage disequilibrium across this 150-kb haplotype. Assays for these markers could diagnose horses with a genetic predisposition to develop obesity. Additionally, discovery of FAM174A function may improve our understanding of the etiology of this troubling illness in the horse and warrants investigation of this locus for a role in metabolic- and obesity-related disorders of other species.

An investigation into the daily level of voluntary activity of stabled riding school horses

The importance of correct feeding practice has been highlighted by the increasing prevalence of obesity in horses. Human research has suggested that voluntary activity (VA) levels may influence digestible energy (DE) requirements, accounting for 15-50% of human daily energy expenditure. Therefore, the aim of this study was to investigate whether levels of non-structured exercise differed between stabled horses with similar bodyweight (BW) and similar structured workloads, but with different estimated DE intakes to maintain their BW. Twelve mature horses were selected based on their estimated DE intake and BW, and were paired according to their BW, breed, estimated DE intake, and structured exercise. Within each pair, one horse (L) was fed a relatively lower estimated DE intake than the other horse (H) to maintain a similar, constant BW and performing similar levels of structured exercise. Estimated DE intake was therefore significantly (P&lt;0.01) different between Group L and Group H. Each pair was observed for 72 h during which structured exercise and non-structured exercise were measured. Heart rate was used as a measure of workload during the structured exercise. Two RT3 accelerometers, located on a roller (RT3-R) and head collar (RT3-H), were used to measure VA levels when stabled in addition to visual observations using focal sampling between 07:00 and 18:00 h. RT3-R and RT3-H activity levels were not significantly (P&gt;0.05) different between individual horses. Median activity counts were significantly (P≤0.001) higher during the day time (06:30-18:29 h) compared to the night time (18:30-06:29 h). However, measured activity using RT3 accelerometers did not show a significant difference between horses in Group L and Group H (P&gt;0.05). It was therefore concluded, that differences in VA levels during stabling could not explain the difference in estimated DE requirements between horses with a similar BW and workload.

Sustained, Low-Intensity Exercise Achieved by a Dynamic Feeding System Decreases Body Fat in Ponies.

BackgroundObesity in horses is increasing in prevalence and can be associated with insulin insensitivity and laminitis. Current treatment strategies for obesity include dietary restriction and exercise. However, whether exercise alone is effective for decreasing body fat is uncertain.HypothesisOur hypothesis was that twice daily use of a dynamic feeding system for 3 months would induce sustained, low‐intensity exercise thereby decreasing adiposity and improving insulin sensitivity (SI).AnimalsEight, university‐owned, mixed‐breed, adult ponies with body condition scores (BCS) ≥5/9 were used.MethodsTwo treatments (“feeder on” or “feeder off”) were administered for a 3‐month period by a randomized, crossover design (n = 4/treatment). An interim equilibration period of 6 weeks at pasture separated the 2 study phases. Measurements of body mass (body weight, BCS, cresty neck score [CrNS], and morphometry), body fat (determined before and after the “feeder on” treatment only), triglycerides, and insulin sensitivity (SI; combined glucose‐insulin test) were undertaken before and after treatments.ResultsThe dynamic feeding system induced a 3.7‐fold increase in the daily distance travelled (n = 6), compared to with a stationary feeder, which significantly decreased mean BCS (6.53 ± 0.94 to 5.38 ± 1.71), CrNS (2.56 ± 1.12 to 1.63 ± 1.06) and body fat (by 4.95%). An improvement in SI did not occur in all ponies.Conclusions and Clinical ImportanceA dynamic feeding system can be used to induce sustained (daily), low‐intensity exercise that promotes weight loss in ponies. However, this exercise may not be sufficient to substantially improve SI.

Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015.

Andalusian horses have been proposed as a breed predisposed to equine metabolic syndrome (EMS) phenotype [1] because they are prone to exhibiting regional, generalised adiposity and tendency to laminitis [2]. Insulin dysregulation represents the main pathophysiological cause for all the features of EMS, however there are no epidemiological studies in this breed. To assess insulin dysregulation through insulin proxies in Andalusian horses with different levels of obesity. Cross-sectional study. One hundred and sixty-four Andalusians (78 stallions and 86 mares, 2-15 years) were scored for overall (body condition score, BCS) and neck (cresty neck score, CNS) adiposity. Grain concentrate was withheld for 12 h before sampling. Blood samples were collected between 06.00-10.00 h for basal glucose, insulin concentrations, RISQI and MIRG proxies calculation. Conditions were defined as: obese horses (Ob), BCS ≥ 7; cresty neck horses (CN), CNS ≥ 3; hyperinsulinaemia, insulin ≥20 μu/ml; low insulin sensitivity, RISQI<0.32[mu/l](-0.5) and increased insulin secretory response, MIRG>5.6muinsulin (2)/[10.l.mgglucose]. Regarding BCS 2 groups were created: Ob and non-Ob. These groups were subdivided depending on CNS: with CN and without it (nonCN). Ob-nonCN group (n = 2) was excluded for the statistics due to the low number of horses. Of the horses studied, 26.8% were Ob-CN, 42.1% were nonOb-CN and 31.1% were nonOb-nonCN. Ob horses presented higher insulin levels (P = 0.034) and lower RISQI values (P = 0.019) than all nonOb horses. When CN was considered, only RISQI was lower (P = 0.015) in Ob-CN group respect to nonOb-nonCN, however nonOb-CN group does not differ from the other 2 groups. Furthermore, the percentage of Ob-CN horses with hyperinsulinaemia (2.3%), abnormal RISQI (4.5%) and MIRG (9.1%) was very low. These results suggest that in Andalusians, increased adiposity was not clearly associated to insulin dysregulation and, similar to human beings, may coexist as a metabolically healthy but obese phenotype. Ethical animal research: Ethical University Committee approved all the procedures and owner informed consent was obtained. None. Competing interests: None declared.

Effect of increased adiposity on insulin sensitivity and adipokine concentrations in horses and ponies fed a high fat diet, with or without a once daily high glycaemic meal.

The relative influences of obesity and adaptation to high glycaemic diets on the development of insulin dysregulation in equids are unclear. To determine whether increased adiposity per se is responsible for the decreased insulin sensitivity often observed in obese horses or whether a dietary glycaemic response is critically important. Randomised controlled trial. Eighteen horses and ponies were studied over a 20-week period. They received ad libitum hay plus either a high fat (low glycaemic) diet (FAT; n = 6) or a similar (isocaloric) diet containing 1.5 g/kg bwt once daily glucose (GLU; n = 6) to induce obesity. A third group received a control ration (CON; n = 6). Adiposity was monitored using body condition score (BCS) and total body fat mass percentage (TBFM) determined using a deuterium oxide dilution technique. Insulin sensitivity was assessed using a frequently sampled i.v. glucose tolerance test. Plasma concentrations of glucose, insulin, leptin, adiponectin, tumour necrosis factor-α (TNF-α) and serum amyloid A (SAA) were measured. The FAT and GLU groups became obese (BCS ≥7) whereas the CON group maintained moderate condition (BCS ≤6). Total body fat mass and leptin concentrations were increased in the FAT and GLU groups than in the CON group (P<0.001 and P = 0.003, respectively). Values for both insulin-dependent (SI) and insulin-independent (Sg) glucose disposal were higher in the GLU group compared with the FAT and CON groups (P = 0.006 and P = 0.03, respectively). There were no differences in adiponectin, TNF-α or SAA between groups (all P≥0.4). Increased adiposity did not reduce insulin sensitivity in either the FAT or the GLU diet groups, suggesting that obesity per se might not be responsible for the lower SI values reported in previous studies. Contrary to expectations, once daily glucose appeared to increase insulin sensitivity. Further work is required into the dietary causes of insulin resistance in equids.

Preliminary investigation into a potential role for myostatin and its receptor (ActRIIB) in lean and obese horses and ponies.

Obesity is a widespread problem across the leisure population of horses and ponies in industrialised nations. Skeletal muscle is a major contributor to whole body resting energy requirements and communicates with other tissues through the secretion of myokines into the circulation. Myostatin, a myokine and negative regulator of skeletal muscle mass, has been implicated in obesity development in other species. This study evaluated gene and protein expression of myostatin and its receptor, ActRIIB in adipose tissues and skeletal muscles and serum myostatin concentrations in six lean and six obese animals to explore putative associations between these factors and obesity in horses and ponies. Myostatin mRNA expression was increased while ActRIIB mRNA was decreased in skeletal muscles of obese animals but these differences were absent at the protein level. Myostatin mRNA was increased in crest fat of obese animals but neither myostatin nor ActRIIB proteins were detected in this tissue. Mean circulating myostatin concentrations were significantly higher in obese than in lean groups; 4.98 ng/ml (±2.71) and 9.00 ng/ml (±2.04) for the lean and obese groups, respectively. In addition, there was a significant positive association between these levels and myostatin gene expression in skeletal muscles (average R2 = 0.58; p<0.05). Together, these results provide further basis for the speculation that myostatin and its receptor may play a role in obesity in horses and ponies.

Impact of water-soaking on the nutrient composition of UK hays

EQUINE metabolic syndrome (EMS), defined as obesity, insulin resistance and an increased risk of laminitis, is becoming increasingly recognised as an important condition with serious welfare implications (Frank and others...

Obesity and the health and welfare of the leisure horse

Abstract Obesity is defined as an accumulation of excess body fat and is a medical disease in which excess fat has accumulated to such an extent that it has an adverse effect on the general health of the horse. Obesity is recognised as a cause for concern with regards to the health and welfare of companion animals, with one in five horses kept for leisure purposes currently regarded as obese. While obesity is not widely regarded as a welfare issue by the general public, owners have a duty of care to prevent pain and suffering in horses, and evidence suggests that an obese horse is more at risk of developing painful conditions such as laminitis. Recognition of obesity in horses is an inherent problem, with many owners underestimating the body condition and weight of their horse; this being further complicated by the fact that with larger framed horses, or horses that are already overweight, assessing body condition is more difficult. There are a number of ways of assessing body condition, including measuring actual bodyweight, assigning a body condition score and using formulas such as the body mass index. Body condition scoring is regarded as subjective, but is the most practical means by which owners can regularly assess the body condition of their horse. As with many diseases/disorders, the cause of obesity is multifactorial; however, the most common reason for a horse to become obese is overfeeding coupled with a lack of exercise. Obesity can be addressed by client education, and the veterinary nurse can provide advice with regards to weight management programmes. However, these need to be tailored to the individual horse, and owners need to recognise that they are entering into a long-term commitment.

Fibre digestibility, abundance of faecal bacteria and plasma acetate concentrations in overweight adult mares.

The purpose of the present study was to compare digestibility of grass hay, faecal and plasma volatile fatty acid (VFA) concentrations, and faecal bacterial abundance in overweight and moderate-condition mares. Five overweight adult mixed-breed mares and five adult mixed-breed mares in moderate condition were housed individually and limit-fed orchard grass (Dactylis glomerata) hay at 20g/kg body weight (as fed) daily for 14 d. Forage DM and fibre digestibility were determined using AOAC methods; digestible energy was measured using bomb calorimetry; plasma and faecal VFA concentrations were determined by use of GC and MS; faecal Firmicutes, Bacteroidetes, Fibrobacter succinogenes, Ruminococcus flavefaciens and total bacteria abundance was determined by quantitative real-time PCR using previously designed phylum-specific 16S ribosomal RNA gene primers. No differences in hay digestibility, faecal VFA concentrations or faecal bacterial abundance were detected between overweight and moderate-condition mares. Mean plasma acetate concentrations were higher (P=0·03) in overweight (1·55 (range 1·43-1·65) mmol/l) v. moderate-condition (1·39 (range 1·22-1·47) mmol/l) mares. We conclude that the higher plasma acetate in overweight mares should be further investigated as a potential link between gut microbes and obesity in horses.

Prevalence and Risk Factors for Owner‐ Reported Obesity in Horses and Ponies in Great Britain

AimsTo estimate prevalence of owner‐reported obesity in British veterinary‐registered horses and ponies, and identify risk factors associated with obesity.MethodsThirty veterinary practices randomly selected horse owners to complete an ethically approved, self‐administered postal questionnaire. Owners estimated body condition score using a modified Carroll and Huntington method (1–6) and animals were classified as obese if they were scored as 5 (fat) or 6 (very fat). Factors associated with obesity were assessed using logistic regression analysis.ResultsOwner‐reported prevalence of obesity was 31.2% (n = 247/792, 95% CI 27.9–34.2). A greater proportion of obese animals (n = 47/225, 20.9%) had a history of laminitis compared with normal/underweight animals (n = 69/511, 13.5%, P = 0.01). Univariable logistic regression analysis identified several management and horse‐level risk factors. Data from 785 horses were included in the final multivariable logistic regression model, and factors associated with an increased risk of obesity were breed (P&lt;0.001), ease of maintaining weight (P&lt;0.001) and primary use (P = 0.002). Compared with Thoroughbreds, draught‐type (odds ratio [OR] 7.3; 95% CI 3.5–17.1), cob‐type (OR 5.8; 95% CI 2.6–12.8), native (OR 3.1; 95% CI 1.7–5.7), and Welsh breeds (OR 3.5; 95% CI 1.9–6.2) were more likely to be obese. Animals described as ‘good doers’ were more likely to be obese compared those described as readily maintaining normal weight (OR 3.7; 95% CI 2.6–5.3). Compared with animals whose primary use was competition, animals predominantly used for pleasure riding were more likely to be obese (OR 2.5; 95% CI 1.4–4.3), and risk increased in non‐ridden horses compared with competition horses (OR 2.9; 95% CI 1.5–5.5, P = 0.002).Conclusion and practical significanceIdentification of breed and other horse characteristics as risk factors for obesity will enable optimal targeting of owner education regarding preventive management to reduce the risk of obesity among the British horse population.Ethical animal researchOwner informed consent was obtained for the questionnaire. Sources of funding: This project was funded by World Horse Welfare. Competing interests: None.

Estimated digestible energy intakes in moderate and overweight horses

Estimated digestible energy intakes in moderate and overweight horses

Adiposity, Plasma Insulin, Leptin, Lipids, and Oxidative Stress in Mature Light Breed Horses

Increased blood insulin levels are associated with an increased risk of pasture-associated laminitis in equids. To determine the relationship between plasma insulin, leptin, and lipid levels, and measures of oxidative stress with adiposity in mature light breed horses. 300 randomly selected light breed horses, aged 4-20 years. A random sample of horses (140 mares, 151 geldings, and 9 stallions) was drawn from the VMRCVM Equine Field Service practice client list. Evaluations occurred June 15 - August 15, 2006, with all sampling performed between 0600 and 1200 hours. Concentrate feed was withheld for at least 10 hours before sampling. Plasma was analyzed for insulin, glucose, leptin, triglycerides, nonesterified fatty acids, and measures of oxidative stress. Body condition score was determined as the average of 2 independent investigators. Overconditioned and obese horses had higher plasma insulin (P < .001) and leptin (P < .01) levels than optimally conditioned horses. Obese horses had higher triglyceride levels (P = .006) and lower red blood cell gluthathione peroxidase activities (P = .001) than optimally conditioned horses. Maintaining horses at a BCS <7 might be important for decreasing the risk of pasture-associated laminitis.

Diurnal rhythm and effects of feeding, exercise and recombinant equine growth hormone on serum insulin concentrations in the horse

As growth hormone increases lean body mass, it could be a therapy for obese horses. However, growth hormone use induces hyperinsulinaemia in some species, so further investigation is warranted. To investigate the effects of feeding, exercise and growth hormone therapy on basal insulin concentrations in healthy horses. In vivo experimental study. Blood samples were obtained every 30 min from 12 geldings over 24 h, to establish basal serum insulin concentrations, before they underwent a 3-week exercise programme. Horses were allocated into 2 groups and exercised for another 4 weeks. Group A received daily i.m. injections of recombinant equine growth hormone; 5 mg/day for 5 days, then 12.5 mg/day for 16 days. Blood samples were taken daily before feeding. Insulin vs. time area under curve of Groups A and B were compared using a Student's unpaired t test. Horses demonstrated insulin peaks within 2 h of feeding of 577 ± 108.3 pmol/l at 09.30 h and 342.4 ± 75.7 pmol/l at 17.30 h, despite receiving the same meal. The nadir was between midnight and 07.30 h. Exercise had no effect on basal insulin concentrations prior to equine growth hormone administrations. The equine growth hormone injections increased serum insulin concentrations (P = 0.01) within Group A, from 44.4 ± 15.3 pmol/l initially to 320.9 ± 238.2 pmol/l by Day 12. Exogenous growth hormone caused variable hyperinsulinaemia, which was alleviated once equine growth hormone administration ceased. Single serum samples taken prior to the morning meal provide basal insulin concentrations. Exercise did not change basal insulin concentrations. However, equine growth hormone injections increased basal insulin concentrations, which were not ameliorated by exercise. This therapy is not recommended to address obesity in insulin-resistant equids.

Progress towards effective prevention and therapy for laminitis

Progress towards effective prevention and therapy for laminitis

Prevalence of Overconditioning in Mature Horses in Southwest Virginia during the Summer

The prevalence of obesity in horses in the eastern United States is not well documented. To determine body condition and risk factors for obesity in horses in Southwest Virginia during summer. A sample of 300 mature (4-20 years old), light breed horses (140 mares, 151 geldings, and 9 stallions) from the VMRCVM Equine Field Service practice equine database. The horses were from 114 farms and 138 owners. Horses were evaluated over a 60-day period in this cross-sectional, prospective study. A questionnaire was completed for each horse. Body condition score (BCS) was assigned using a scale of 1 (emaciated) to 9 (obese) by 2 independent scorers. Morphometric measurements included average neck circumference (ANC), girth, body length, and height at the withers. Horses were categorized based on BCS as underconditioned (BCS < 4), optimal condition (BCS 4-6), overconditioned (BCS 7), and obese condition (BCS 8-9). Five horses (1.7%) were underconditioned, 142 horses (47.3%) were optimally conditioned, 97 horses (32.3%) were overconditioned, and 56 (18.7%) were obese. Estimated body weight (EBW) (r = 0.14, P = .015), body mass index (BMI) (r = 0.46, P < .001), and neck circumference to height ratio (NCHR) (r = 0.50, P = .001) increased with increasing BCS. The prevalence of overconditioned and obese horses in this population was higher than reported in previous studies and indicates that obesity might be an emerging problem in horses.