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The purpose of the current study was to examine the influence of dietary composition on short-term endurance training-induced adaptations of substrate partitioning and time trial exercise performance. Eight untrained males cycled for 90 min at approximately 54% aerobic capacity while being infused with [6,6(2)H]glucose before and after two 10-d experimental phases separated by a 2-week washout period. Time trial performance was measured after the 90-min exercise trials before and after the 2nd experimental phase. During the first 10-d phase, subjects were randomly assigned to consume either a high carbohydrate or high fat diet while remaining inactive (CHO or FAT). During the second 10-d phase, subjects consumed the opposite diet, and both groups performed identical daily supervised endurance training (CHO+T or FAT+T). CHO and CHO+T did not affect exercise metabolism. FAT reduced glucose flux at the end of exercise, while FAT+T substantially increased whole body lipid oxidation during exercise and reduced glucose flux at the end of exercise. Despite these differences in adaptation of substrate use, training resulted in similar improvements in time trial performance for both groups. We conclude that (a) 10-d high fat diets result in substantial increases in whole body lipid oxidation during exercise when combined with daily aerobic training, and (b) diet does not affect short-term training-induced improvements in high-intensity time trial performance. [ABSTRACT FROM AUTHOR]

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., (© 2020 Stichting International Foundation for Animal Genetics.)

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 (h 2 SNP ) 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 h 2 SNP estimates that were considered moderately to highly heritable (h 2 SNP >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 h 2 SNP 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 h 2 SNP 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 h 2 SNP 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., (© 2018 EVJ Ltd.)

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., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Physical activity has been shown to improve insulin sensitivity in subjects with insulin resistance, but the effect of athletic conditioning on subjects with normal insulin sensitivity has received less scrutiny. Because strenuous exercise can be limited by the availability of substrates, it is reasonable to hypothesize that conditioning would increase the capacity for muscle uptake of substrates like glucose and to the extent that improvement in this process would include upregulation of the portions of the glucose uptake pathway in muscle, this increased capacity would also be reflected in insulin sensitivity. Therefore, we tested the hypothesis that conditioning for endurance exercise would result in increased insulin sensitivity using elite racing sled dogs., Methods: A frequent-sampled intravenous glucose tolerance test was performed on these dogs before and after a full 7-month season of conditioning in preparation for a 1600-km race., Results: Compared with the results in unconditioned dogs, conditioned dogs rapidly cleared the intravenous glucose bolus through increases in both glucose mediated (7.6%·min ± 3.4%·min vs 3.0%·min ± 2.2%·min, P = 0.008) and insulin-mediated (36.3 ± 18.4 × 10 L·min·mU vs 11.5 ± 8.0 × 10 L·min·mU, P = 0.007) mechanisms. The more modest increase in serum insulin after the intravenous glucose bolus in conditioned dogs failed to suppress lipolysis and serum concentrations of nonesterified fatty acids remained constant in the conditioned dogs throughout the 4-h test., Conclusions: These results, in particular the increase in insulin-independent peripheral uptake of glucose, describe novel alterations in metabolism induced by athletic conditioning that arguably result in near-continuous provision of oxidizable substrates to peripheral muscle in support of sustained muscular work typical of these dogs.

Background: Age and diet may affect insulin sensitivity (SI) but these factors have received limited investigation in horses., Objectives: To measure minimal model parameters during an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) after adaptation to a forage only diet (HAY) or forage supplemented with either starch/sugar-rich (SS) or oil/fibre-rich (FF) concentrate feeds; and to assess glucose and insulin responses to a standardised meal challenge (SMC, 4 g/kg BW of SS) after diet adaptation in adult and aged mares., Study Design: Latin square design with eight adult (5-12 years) and nine aged (>19 years) healthy mares., Methods: Diets were fed for 6 weeks, and the FSIGTT and SMC were performed after 31-32 and 41 days on each diet respectively. Data were analysed by a mixed ANOVA for repeated measures., Results: Acute insulin response to glucose (AIRg) was greater and SI was lower in aged horses, compared with adults, regardless of diet. Both AIRg and SI were greater in aged mares after adaptation to SS, as compared with HAY. Similar trends, although not statistically significant, were observed after adaptation to SS in adult mares. Peak insulin concentration and area under the insulin vs. time curve during the SMC were greater in aged than adult mares with all diets. Furthermore, area under the glucose vs. time curve was lower after adaptation to SS, when compared with other diets, in both groups., Main Limitations: Transient weight loss occurred at the beginning of the study and only one sex was included. Incomplete ingestion of the SMC by four mares was another limitation., Conclusions: Insulin responses to i.v. and enteral nonstructural carbohydrate challenge increase with age in healthy horses, regardless of diet fed., (© 2018 EVJ Ltd.)

OBJECTIVE To investigate risk factors for the development of pasture- and endocrinopathy-associated laminitis (PEAL) in horses and ponies in North America. DESIGN Case-control study. ANIMALS 199 horses with incident cases of PEAL and 351 horses from 2 control populations (healthy horses [n = 198] and horses with lameness not caused by laminitis [153]) that were evaluated in North America between January 2012 and December 2015 by veterinarian members of the American Association of Equine Practitioners. PROCEDURES North American members of the American Association of Equine Practitioners were contacted to participate in the study, and participating veterinarians provided historical data on incident cases of PEAL, each matched with a healthy control and a lameness control. Conditional logistic regression analysis was used to compare data on PEAL-affected horses with data on horses from each set of controls. RESULTS Horses with an obese body condition (ie, body condition score ≥ 7), generalized or regional adiposity (alone or in combination), preexisting endocrinopathy, or recent (within 30 days) glucocorticoid administration had increased odds of developing PEAL, compared with horses that did not have these findings. CONCLUSIONS AND CLINICAL RELEVANCE The present study identified several risk factors for PEAL that may assist not only in managing and preventing this form of laminitis, but also in guiding future research into its pathogenesis.

Background: Metabolomics, the study of small-molecule metabolites, has increased understanding of human metabolic diseases, but has not been used to study equine metabolic syndrome (EMS)., Objectives: (1) To examine the serum metabolome of Welsh Ponies with and without insulin dysregulation before and during an oral sugar test (OST). (2) To identify differences in metabolites in ponies with insulin dysregulation, obesity, or history of laminitis., Animals: Twenty Welsh Ponies (mean ± SD; 13.8 ± 9.0 years) classified as non-insulin dysregulated [CON] (n = 10, insulin < 30 mU/L) or insulin dysregulated [ID] (n = 10, insulin > 60 mU/L) at 75 minutes after administration of Karo syrup, obese (n = 6) or nonobese (n = 14), and history of laminitis (n = 9) or no history of laminitis (n = 11)., Methods: Case-control study. Metabolomic analysis was performed on serum obtained at 0 minutes (baseline) and 75 minutes during the OST. Data were analyzed with multivariable mixed linear models with significance set at P ≤ .05., Results: Metabolomic analysis of 646 metabolites (506 known) detected significant metabolite differences. At baseline, 55 metabolites (insulin response), 91 metabolites (obesity status), and 136 metabolites (laminitis history) were different. At 75 minutes, 51 metabolites (insulin response), 102 metabolites (obesity status), and 124 metabolites (laminitis history) were different., Conclusions and Clinical Importance: Use of metabolomics could have diagnostic utility for early detection of EMS and provide new knowledge regarding the pathophysiology of metabolic perturbations associated with this condition that might lead to improved clinical management., (Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Diagnosis of equine pituitary pars intermedia dysfunction (PPID) remains a challenge as multiple factors (stress, exercise, and time of year) influence ACTH and cortisol concentrations. To assess endocrine status in a study designed to evaluate the effects of age and diet on glucose and insulin dynamics, we performed thyrotropin-releasing hormone (TRH) stimulation tests and overnight dexamethasone suppression tests in March, May, August, and October on 16 healthy Thoroughbred and Standardbred mares and geldings. Horses were grouped by age: adult (mean ± SD; 8.8 ± 2.9 yr; n = 8) and aged (20.6 ± 2.1 yr; n = 8). None of the horses showed clinical signs (hypertrichosis, regional adiposity, skeletal muscle atrophy, lethargy) of pituitary pars intermedia dysfunction. Horses were randomly assigned to groups of 4, blocked for age, and fed grass hay plus 4 isocaloric concentrate diets (control, starch-rich, fiber-rich, and sugar-rich) using a balanced Latin square design. Data were analyzed using a multivariable linear mixed regression model. Baseline ACTH was significantly higher in aged horses (mean ± standard error of the mean; 60.0 ± 10.7 pg/mL) adapted to the starch-rich diet compared to adult horses (15.7 ± 12.0 pg/mL) on the same diet (P = 0.017). After controlling for age and diet, baseline ACTH concentrations were significantly increased in October (57.7 ± 7.1 pg/mL) compared to March (13.2 ± 7.1 pg/mL; P < 0.001), May (12.4 ± 7.1 pg/mL; P < 0.001), and August (24.2 ± 7.1 pg/mL; P < 0.001), whereas post-TRH ACTH was higher in August (376.6 ± 57.6 pg/mL) and October (370.9 ± 57.5 pg/mL) compared to March (101.9 ± 57.3 pg/mL; P < 0.001) and May (74.5 ± 57.1 pg/mL; P < 0.001). Aged horses had significantly higher post-dexamethasone cortisol on the starch-rich diet (0.6 ± 0.1 μg/dL) compared to the sugar-rich diet (0.2 ± 0.1 μg/dL; P = 0.021). Post-dexamethasone cortisol was significantly higher in October (0.6 ± 0.1 μg/dL) compared to March (0.3 ± 0.1 μg/dL; P = 0.005), May (0.2 ± 0.1 μg/dL; P < 0.001), and August (0.3 ± 0.1 μg/dL; P = 0.004). Breed did not influence ACTH or cortisol measurements. In conclusion, in addition to age and time of year, diet is a potential confounder as animals on a starch-rich diet may be incorrectly diagnosed with pituitary pars intermedia dysfunction., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Glucose and insulin dynamics may be different in adult and aged horses., Objectives: To determine the effects of age and dietary carbohydrates on glucose and insulin dynamics in healthy horses., Study Design: Balanced Latin square with four isocaloric diets: CONTROL (hay plus restricted-starch-and-sugar fortified pellets), STARCH (control plus kibbled corn), FIBER (control plus unmolassed sugar beet pulp/soybean hull pellets) and SUGAR (control plus dextrose powder)., Methods: A total of 16 healthy Thoroughbreds and Standardbreds divided into two age groups: ADULT (8.8 ± 2.9 years; n = 8) and AGED (20.6 ± 2.1 years; n = 8). Following dietary adaptation, horses underwent an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT), modified oral sugar test (OST) and dietary meal challenge. Outcome variables included: insulin sensitivity (SI), disposition index (DI), glucose effectiveness (Sg) and acute insulin response to glucose (AIRg) from the FSIGTT; peak glucose, peak insulin, time to peak, area under the curve for glucose (AUCg) and insulin (AUCi) from the OST and dietary meal challenge. Data were analyzed using multivariable linear mixed regression modelling., Results: AIRg was higher in AGED (mean [95% confidence interval]; 582.0 [455.0-709.0]) vs. ADULT (358.0 [224.0-491.0]; P = 0.03). ADULT and AGED horses had a higher SI on STARCH (adult: 3.3 [2.3-4.2]; aged: 2.8 [1.9-3.7]) and SUGAR (adult: 3.4 [2.5-4.3]; aged: 4.0 [3.1-4.9]) diets compared with CONTROL (adult: 2.0 [1.1-2.9], P = 0.029 (starch), P = 0.009 (sugar); aged: 1.4 [0.5-2.2], P = 0.009 (starch), P < 0.001 (sugar)). Feeding a STARCH (adult: 21581.0 [15029.0-28133.0]; aged: 35205.0 [29194.0-41216.0]) or SUGAR (adult: 26050.0 [19885.0-32215.0]; aged: 25720.0 [19770.0-31670.0]) meal resulted in postprandial hyperinsulinaemia (AUCi)., Main Limitations: Study cohort contained two insulin-sensitive breeds and no insulin-resistant breeds., Conclusions: Age and diet should be considered when evaluating glucose and insulin dynamics., (© 2017 EVJ Ltd.)

Background: Insulin dysregulation, obesity, and exposure to high-nonstructural carbohydrate (NSC) forage are risk factors for equine metabolic syndrome-associated laminitis (EMSAL); high systemic insulin concentrations in EMSAL are proposed to induce cellular dysregulation in the digital lamellae through activation of the insulin-like growth factor-1 receptor., Objectives: To use a dietary challenge model (DCM) and a euglycaemic-hyperinsulinaemic clamp (EHC) model to assess lamellar growth factor-related signalling., Study Design: Lamellar phospho (P)-protein concentrations of signalling proteins important in growth factor-related signalling were assessed in 2 models: 1) lean and obese ponies on a low- or high-NSC diet; and 2) EHC model using Standardbred horses., Methods: Ponies stratified for body condition (lean [LN, n = 11] and obese [OB, n = 11]) were exposed to a low-NSC diet (LO, n = 5 per group for LN LO and OB LO) or a high NSC diet (HI, n = 6 per group for LN HI and OB HI groups) for 7 days. For the EHC model, horses were administered insulin (constant rate infusion [6 mIU/kg bwt/min] combined with 50% dextrose, EHC group, n = 8)] or saline (0.57 mL/kg bwt/h, CON group, n = 8) for 48 h. Immunoblotting was employed to assess concentrations of activated/phosphorylated and total protein for members of the PI3K/Akt/mTORC1 and Ras/ERK pathways in lamellar samples from both models., Results: In the DCM, lamellar P-(Ser 240/244) RPS6 was increased in OB HI ponies (vs. OB LO, P<0.05); positive correlations existed (P<0.05; r>0.5) between Day 7 basal serum insulin concentrations and lamellar concentrations of P-p70S6K and P-(Ser 240/244) RPS6. In the EHC model, lamellar concentrations of P-Akt, P-p70S6K, P-ERK 1/2, P-p90RSK, and both P-(Ser 235/236) and P-(Ser 240/244) RPS6 were increased in the EHC group (vs. CON, P<0.05)., Main Limitations: The primary limitations of this study are the small number of animals per group in the DCM study, and the fact that many animals did not develop laminitis as that was not the endpoint of either study., Conclusions: These results support further investigation of mTORC1/RPS6 signalling as a potential therapeutic target(s) in EMSAL. The Summary is available in Chinese - see Supporting Information., (© 2017 EVJ Ltd.)

Reasons for Performing Study: Hyperinsulinaemia is implicated in the pathogenesis of endocrinopathic laminitis. Insulin can bind to different receptors: two insulin receptor isoforms (InsR-A and InsR-B), insulin-like growth factor-1 receptor (IGF-1R) and InsR/IGF-1R hybrid receptor (Hybrid). Currently, mRNA expression of these receptors in equine tissues and the influence of body type and dietary carbohydrate intake on expression of these receptors is not known., Objectives: The study objectives were to characterise InsR-A, InsR-B, IGF-1R and Hybrid expression in lamellar tissue (LT) and insulin responsive tissues from horses and examine the effect of dietary nonstructural carbohydrate (NSC) on mRNA expression of these receptors in LT, skeletal muscle, liver and two adipose tissue (AT) depots of lean and obese ponies., Study Design: In vivo experiment., Methods: Lamellar tissue samples were evaluated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) for receptor mRNA expression (n = 8) and immunoblotting for protein expression (n = 3). Archived LT, skeletal muscle, liver and AT from lean and obese mixed-breed ponies fed either a low (~7% NSC as dry matter; 5 lean, 5 obese) or high NSC diet (~42% NSC as dry matter; 6 lean, 6 obese) for 7 days were evaluated by RT-qPCR to determine the effect of body condition and diet on expression of the receptors in different tissues. Significance was set at P≤0.05., Results: Lamellar tissue expresses both InsR isoforms, IGF-1R and Hybrid. LT IGF-1R gene expression was greater than either InsR isoform and InsR-A expression was greater than InsR-B (P≤0.05). Obesity significantly lowered IGF-1R, InsR-A and InsR-B mRNA expression in LT and InsR-A in tailhead AT. High NSC diet lowered expression of all three receptor types in liver; IGF-1R and InsR-A in LT and InsR-A in tailhead AT., Conclusions: Lamellar tissue expresses IGF-1R, InsR isoforms and Hybrids. The functional characteristics of these receptors and their role in endocrinopathic laminitis warrants further investigation., (© 2015 EVJ Ltd.)

Reasons for Performing Study: Increased serum nonesterified fatty acids (NEFA) and decreased serum electrolytes are linked to abdomasal displacements in post partum dairy cattle. Post partum colic in mares may be associated with metabolic changes specific to pregnancy and the periparturient period., Objectives: To determine if fluctuations in serum NEFA, ionised calcium (iCa) and magnesium (iMg) occurred in periparturient mares and if these alterations were associated with post partum colic., Study Design: Longitudinal observational study., Methods: Mares from 3 farms in central Kentucky were enrolled. Blood samples were collected 14 days prior to the estimated foaling date, within 4 days post parturition, and 14 and 28 days after foaling for batch analysis of serum NEFA, iCa and iMg. Health information was provided by farm managers and veterinarians. Data were analysed using Kruskal-Wallis χ(2) statistic for nonparametric data and a matched case/control approach. Repeated measures logistic regression models were developed., Results: Serum NEFAs were higher at 14-1 day before foaling (mean ± s.d., mmol/l), 0.28 ± 0.12, P = 0.04 and from foaling to 4 days after foaling, 0.29 ± 0.20 (P = 0.05) in mares that developed colic compared with those that did not colic, 0.19 ± 0.05 and 0.21 ± 0.14, respectively. Ionised calcium was lower at 15-28 days post foaling in mares that showed colic, 1.50 ± 0.17 compared to mares that did not colic, 1.60 ± 0.12, P = 0.02. Risk of colic in post partum mares increased 38% for each 0.1 mmol/l increase in serum NEFA (odds ratio = 1.38, 95% confidence interval 1.06-1.81, P = 0.02)., Conclusions: Mares with post partum colic had significantly higher serum NEFA and lower iCa prior to the colic episode compared with mares that did not develop colic. Monitoring these metabolic alterations may lead to predictive and preventive colic strategies for post partum mares., (© 2015 EVJ Ltd.)

Reasons for Performing Study: Acute, massive enteral carbohydrate overload is associated with laminar inflammation in equids; it is unclear if the same is true for a more prolonged period of moderate dietary carbohydrate intake., Objectives: To characterise laminar inflammation in ponies exposed to a dietary carbohydrate challenge meant to mimic acute pasture exposure., Study Design: In vivo experiment., Methods: Mixed-breed ponies (n = 22) received a diet of hay chop (nonstructural carbohydrate [NSC] ∼7% on a dry matter [DM] basis) for 4 weeks prior to initiation of the experimental feeding protocol. Following dietary acclimation, ponies were stratified into either Lean (n = 11, body condition score [BCS] ≤4) or Obese (n = 11, BCS ≥7) groups and each group further stratified to either remain on the control, low NSC diet (n = 5 each for Obese and Lean) or receive a high NSC diet (hay chop supplemented with sweet feed and oligofructose, total diet ∼42% NSC; n = 6 each for Obese and Lean) for a period of 7 days. Laminar samples were collected following euthanasia and sections stained immunohistochemically for CD163, MAC387/calprotectin and cyclo-oxygenase-2 (COX-2) using commercially available antibodies. The number of CD163 (+) and MAC387(+) cells was quantified for each section; the distribution of COX-2 expression was qualitatively assessed. Laminar mRNA concentrations of several proinflammatory molecules (interleukin-1β [IL-1β], IL-6, tumour necrosis factor-α [TNFα], IL-8, IL-10, monocyte chemoattractant protein-1 [MCP-1], MCP-2), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), E-selectin, plasminogen activator inhibitor-1 (PAI-1) and COX-2 were evaluated using real-time quantitative polymerase chain reaction (qPCR)., Results: High carbohydrate feeding resulted in no increase in laminar proinflammatory cytokine expression; laminar COX-2 expression was increased by high carbohydrate feeding. No laminar leucocyte infiltration was observed in response to high carbohydrate feeding., Conclusions: These results suggest that the marked laminar inflammation observed in models of sepsis-associated laminitis may not play a central role in the pathophysiology of pasture-associated laminitis., (© 2014 EVJ Ltd.)

Objective: To compare, in horses, estimates of insulin sensitivity obtained from minimal model analysis (MMA) of a frequently sampled IV glucose tolerance test (FSIGTT) with estimates from the euglycemic-hyperinsulinemic clamp (EHC) and to evaluate the validity of surrogate estimates of insulin sensitivity derived from an oral glucose tolerance test (OGTT)., Animals: 18 mature Standardbreds (mean ± SD body weight, 428.9 ± 35.9 kg; mean ± SD body condition score, 4.4 ± 1.0 [on a scale of 1 to 9])., Procedures: All horses underwent at least 2 of the 3 procedures (EHC [n = 15], insulin-modified FSIGTT [18], and OGTT [18]) within a 10-day time frame to evaluate insulin sensitivity., Results: Insulin sensitivity variables derived from the EHC and FSIGTT were strongly correlated (r = 0.88). When standardized to the same units of measure, these measures were still strongly correlated (r = 0.86) but were not equivalent. Area under the curve, peak insulin concentration, insulin concentration at 120 minutes, and 2 calculated indices from glucose and insulin data from the OGTT were significantly correlated with the EHC- and FSIGTT-derived estimates of insulin sensitivity., Conclusions and Clinical Relevance: In healthy Standardbreds with moderate body condition score, insulin sensitivities from the EHC and FSIGTT were strongly correlated but not equivalent. Estimates derived from an OGTT also may be useful to estimate insulin sensitivity.

Reasons for Performing the Study: Recent research suggested that prophylactic digital cryotherapy (ICE) improved lameness scores, diminished histological changes and early laminar inflammatory signalling in horses following oligofructose administration. In clinical practice, horses at risk for sepsis-associated laminitis receive ICE. Evidence to support this practice is lacking., Objectives: To determine factors associated with development of laminitis in horses diagnosed with colitis, including ICE., Study Design: Multicentre retrospective case series., Methods: Medical records for horses admitted to 2 university hospitals diagnosed with colitis with evidence of systemic inflammatory response from 2002 to 2012 were reviewed. Horses were excluded if they exhibited signs of laminitis at admission, were ponies, miniature or draught breeds, or <2 years old. Data were analysed using univariate and multivariate logistic regression., Results: Twenty-seven of 130 horses (21%) developed laminitis. Seven of 69 (10%) horses treated with ICE developed laminitis compared with 20/61 (33%) horses that developed laminitis but did not receive ICE. Factors associated with laminitis included site of hospitalisation, admission respiratory rate (↑) and blood L-lactate (↑), and ICE (↓), P<0.05. Horses treated with ICE had 10 times less odds of developing laminitis compared with horses treated without ICE (odds ratio 0.11, 95% confidence limit 0.03-0.44). Sixteen horses (16/130, 12%) were subjected to euthanasia in hospital. Fourteen of these horses had laminitis and 2 did not develop laminitis. Survival for horses with colitis that developed laminitis was 13/27 (48%) compared with survival for horses with colitis that did not develop laminitis, 101/103 (98%)., Conclusion: Laminitis occurred in more clinically compromised horses. Use of ICE reduced the incidence of clinical laminitis in the study population suggesting that digital cryotherapy is an effective prophylactic strategy for the prevention of laminitis in horses with colitis., (© 2013 EVJ Ltd.)

Background: In EMS-associated laminitis, laminar failure may occur in response to energy failure related to insulin resistance (IR) or to the effect of hyperinsulinemia on laminar tissue. 5'-Adenosine-monophosphate-activated protein kinase (AMPK) is a marker of tissue energy deprivation, which may occur in IR., Hypothesis/objectives: To characterize tissue AMPK regulation in ponies subjected to a dietary carbohydrate (CHO) challenge., Animals: Twenty-two mixed-breed ponies., Methods: Immunohistochemistry and immunoblotting for total AMPK and phospho(P)-AMPK and RT-qPCR for AMPK-responsive genes were performed on laminar, liver, and skeletal muscle samples collected after a 7-day feeding protocol in which ponies stratified on body condition score (BCS; obese or lean) were fed either a low-CHO diet (ESC + starch, approximately 7% DM; n = 5 obese, 5 lean) or a high-CHO diet (ESC + starch, approximately 42% DM; n = 6 obese, 6 lean)., Results: 5'-Adenosine-monophosphate-activated protein kinase was immunolocalized to laminar keratinocytes, dermal constituents, and hepatocytes. A high-CHO diet resulted in significantly decreased laminar [P-AMPK] in lean ponies (P = .03), but no changes in skeletal muscle (lean, P = .33; obese, P = .43) or liver (lean, P = .84; obese, P = .13) [P-AMPK]. An inverse correlation existed between [blood glucose] and laminar [P-AMPK] in obese ponies on a high-CHO diet., Conclusions and Clinical Importance: Laminar tissue exhibited a normal response to a high-CHO diet (decreased [P-AMPK]), whereas this response was not observed in liver and skeletal muscle in both lean (skeletal muscle, P = .33; liver, P = .84) and obese (skeletal muscle, P = .43; liver, P = .13) ponies., (Copyright © 2014 by the American College of Veterinary Internal Medicine.)

Little is known about the role insulin plays in regulating whole-body and muscle protein metabolism in horses. The objective of this study was to determine the effects of graded rates of insulin infusion on plasma amino acid concentrations and the activation of factors in the mechanistic target of rapamycin signaling pathway in the skeletal muscle of horses. Isoglycemic, hyperinsulinemic clamp procedures were conducted in 8 mature, thoroughbred mares receiving 4 rates of insulin infusion: 0 mU · kg(-1) · min(-1) (CON), 1.2 mU · kg(-1) · min(-1) (LOWINS), 3 mU · kg(-1) · min(-1) (MEDINS), and 6 mU · kg(-1) · min(-1) (HIGHINS). Blood samples were taken throughout the clamp procedures to measure plasma amino acid concentrations, and a biopsy from the gluteus medius muscle was collected at the end of the 2-h clamp to measure phosphorylation of protein kinase B, eukaryotic initiation factor 4E-binding protein 1, and riboprotein S6. Plasma concentrations of most of the essential amino acids decreased (P < 0.05) after 120 min of insulin infusion in horses receiving the LOWINS, MEDINS, and HIGHINS treatments, with the largest decreases occurring in horses receiving the MEDINS and HIGHINS treatments. Phosphorylation of protein kinase B, 4E-binding protein 1, and riboprotein S6 increased with all 3 rates of insulin infusion (P > 0.05), relative to CON, with maximum phosphorylation achieved with MEDINS and HIGHINS treatments. These results indicate that insulin stimulates whole-body and muscle protein synthesis in mature horses., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The objective of this study was to determine whether the rate of insulin infusion during isoglycemic hyperinsulinemic clamp procedures affected measures of insulin action, including glucose disposal and plasma non-esterified fatty acid, endothelin-1, and nitric oxide concentrations, in mature, healthy horses. Eight thoroughbred mares were studied during a 2-h hyperinsulinemic clamp procedure, conducted at each of 4 rates of insulin infusion: 0 (CON), 1.2 (LOWINS), 3 (MEDINS), and 6 (HIGHINS) mU · kg(-1) · min(-1). The infusion rate of a dextrose solution was adjusted throughout the clamp procedures to maintain blood glucose levels within 10% of baseline glucose concentrations. Plasma insulin concentrations were measured throughout the clamp procedures, and used with the rate of glucose infusion to calculate the plasma insulin concentration-to-rate of glucose infusion ratio, a measure of insulin action on glucose disposal. The rate of glucose infusion increased with rate of insulin infusion (P < 0.05). The plasma insulin concentration-to-rate of glucose infusion ratio was highest for the LOWINS treatment (P < 0.05) and decreased by 62% (P < 0.05) and 84% (P < 0.05) for the MEDINS and HIGHINS treatments, respectively. Although plasma non-esterified fatty acid concentrations were lower than baseline by t = 30 min of the clamp procedures in the LOWINS, MEDINS, and HIGHINS treatments (P < 0.05), the decline was similar for all 3 rates of insulin infusion. Jugular vein plasma nitric oxide and endothelin-1 concentrations were not affected by insulin infusion rate (P > 0.05). The data indicate that it is important to standardize insulin infusion rate if data are to be compared between hyperinsulinemic clamp studies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Reasons for Performing Study: Hypoxia-inducible factor-1α (HIF-1A) is an important protein in the regulation/induction of many genes in the cellular and tissue response to hypoxia and a central mediator in inflammatory signalling. As both hypoxia and inflammatory events are purported to occur in the lamellar epidermis in sepsis-related laminitis in the equid, HIF-1A may play a central role in this disease process., Objectivess: To assess the regulation of HIF-1A and HIF-1A-related genes in the equine keratinocyte in vitro and in the lamellar tissue of horses with sepsis-related laminitis., Study Design: In vivo and in vitro experiments., Methods: Real-time quantitative PCR (RT-qPCR) and immunoblotting were performed to assess the mRNA and protein concentrations of HIF-1A and the mRNA concentrations of HIF-1A-related genes in cultured equine keratinocytes and in lamellar samples from black walnut extract (BWE)- and carbohydrate overload (CHO)-induced laminitis. Hypoxia-inducible factor-1α was further localised via indirect immunofluorescence in frozen lamellar tissue sections., Results: Hypoxia-inducible factor-1α appears to be regulated primarily at the post transcriptional level in the cultured equine keratinocyte, resulting in increased HIF-1A in response to hypoxia but not to lipopolysaccharide exposure. Hypoxia-inducible factor-1α is present at high concentrations in the normal equine lamina, and is increased in Obel grade 1 (OG1) stage laminitis in the CHO model of laminitis. Equine lamellar mRNA concentrations of cyclo-oxygenase-2 and inducible nitric oxide synthase, but not glucose transporter 1, are increased in the BWE and CHO models of laminitis., Conclusions and Potential Relevance: These data indicate that the normal equine lamellae are profoundly hypoxic in comparison with other tissues. The increased mRNA concentrations of cyclo-oxygenase-2 and inducible nitric oxide synthase 2 in equine keratinocytes exposed to hypoxia and lipopolysaccharide, and in lamellar tissue from BWE and CHO models of sepsis-related laminitis, suggest that the marked lamellar inflammatory gene expression in sepsis-related laminitis may be due to an interaction of constitutively high lamellar keratinocyte HIF-1A signalling with inflammatory signalling, possibly induced by circulating inflammatory mediators., (© 2013 EVJ Ltd.)

Faecal samples were collected from seventeen animals, each fed three different diets (high fibre, high fibre with a starch rich supplement and high fibre with an oil rich supplement). DNA was extracted and the V1-V2 regions of 16SrDNA were 454-pyrosequenced to investigate the faecal microbiome of the horse. The effect of age was also considered by comparing mature (8 horses aged 5-12) versus elderly horses (9 horses aged 19-28). A reduction in diversity was found in the elderly horse group. Significant differences between diets were found at an OTU level (52 OTUs at corrected Q<0.1). The majority of differences found were related to the Firmucutes phylum (37) with some changes in Bacteroidetes (6), Proteobacteria (3), Actinobacteria (2) and Spirochaetes (1). For the forage only diet,with no added starch or oil, we found 30/2934 OTUs (accounting for 15.9% of sequences) present in all horses. However the core (i.e. present in all horses) associated with the oil rich supplemented diet was somewhat smaller (25/3029 OTUs, 10.3% ) and the core associated with the starch rich supplemented diet was even smaller (15/2884 OTUs, 5.4% ). The core associated with samples across all three diets was extremely small (6/5689 OTUs accounting for only 2.3% of sequences) and dominated by the order Clostridiales, with the most abundant family being Lachnospiraceae. In conclusion, forage based diets plus starch or oil rich complementary feeds were associated with differences in the faecal bacterial community compared with the forage alone. Further, as observed in people, ageing is associated with a reduction in bacterial diversity. However there was no change in the bacterial community structure in these healthy animals associated with age.

This study tested the hypotheses that age-induced alteration in cortisol, ACTH, and glucose concentrations are due to differences in the response of the hypothalamic-pituitary-adrenal axis and that exercise training would attenuate these differences. Six old (22.0±0.7 yr; mean±SE) and 6 young (7.3±0.6 yr) unfit Standardbred mares ran 3 graded exercise tests (GXT): before (GXT1), after 8 wk of training (GXT2), and at study end at 15 wk (GXT3). Mares trained 3 d/wk at 60% maximum heart rate. Each mare underwent 5 endocrine stimulation tests pre- and posttraining: 1) control (CON), 2) adrenocorticotropin hormone (ACTHtest), 3) combined dexamethasone suppression/ACTH (DEX/ACTH), 4) dexamethasone suppression (DEX), and 5) combined DEX/corticotropin releasing factor (DEX/CRF). For CON, there was no difference in plasma cortisol between age groups pretraining (P=0.19), but young mares had a 102% higher mean (P=0.02) plasma cortisol concentration than old mares posttraining. The pretraining ACTHtest showed young mares had a 72% higher (P=0.05) overall plasma cortisol concentration compared to old. There was no overall age difference in cortisol in the posttraining ACTHtest, but old mares still had lower cortisol concentrations at 30 min during the test, suggesting decreased adrenal response to ACTH stimulation. There was no difference in cortisol response between old and young mares in DEX, DEX/ACTH, or DEX/CRF tests. Young mares had higher (P=0.02) overall plasma cortisol concentration posttraining in response to DEX/ACTH, but old mares showed no change. In CON and DEX/CRF, there were no age differences in plasma ACTH concentration, pre- or posttraining. Pretraining, there was no age difference in glucose response to DEX, but posttraining old mares had a 4% (P=0.04) lower overall plasma glucose concentration compared to young. Posttraining, old mares had lower mean plasma glucose concentrations during DEX compared to pretraining (P=0.02), but there was no change pre- vs. posttraining in young mares (P=0.19). Old and young mares had lower plasma glucose concentrations posttraining during DEX/ACTH (P<0.001 and P=0.05, respectively) and DEX/CRF (P<0.001 and P=0.003, respectively) compared to pretraining. Both the pituitary and adrenal glands experience a decline in function with age although the exact mechanisms behind such changes remain unknown. Exercise training facilitates the counteraction of these deficits.

Reasons for Performing Study: Hyperinsulinaemia has been implicated in the pathogenesis of laminitis; however, laminar cell types responding to insulin remain poorly characterised., Objectives: To identify laminar cell types expressing insulin receptor (IRc) and/or insulin-like growth factor-1 receptor (IGF-1R); and to evaluate the effect of dietary nonstructural carbohydrate (NSC) on their expression., Methods: Mixed-breed ponies (n = 22) received a conditioning hay chop diet (NSC ∼6%); following acclimation, ponies were stratified into lean (n = 11, body condition score [BCS]≤4) or obese (n = 11, BCS ≥7) groups and each group further stratified to remain on the low NSC diet (n = 5 each for obese and lean) or receive a high NSC diet (total diet ∼42% NSC; n = 6 each for obese and lean) for 7 days. Laminar samples were collected at the end of the feeding protocol and stained immunohistochemically for IRc and IGF-1R. The number of IRc(+) cells was quantified; distribution of IGF-1R was qualitatively described. Laminar IRc content was assessed via immunoblotting., Results: The number of IRc(+) cells was greater in the laminae of high NSC ponies than low NSC ponies (P = 0.001); there was a positive correlation between the change in serum insulin concentration and number of IRc(+) cells (r(2) = 0.74; P<0.0001). No epithelial IRc(+) cells were observed; IRc(+) cells were absent from the deep dermis. Analysis of serial sections identified IRc(+) cells as endothelial cells. The distribution of IGF-1R was more extensive than that of IRc, with signal in vascular elements, epithelial cells and fibroblasts., Conclusions: Increased dietary NSC results in increased laminar endothelial IRc expression. Laminar keratinocytes do not express IRc, suggesting that insulin signalling in laminar epithelial cells must be mediated through other receptors (such as IGF-1R)., Potential Relevance: Manipulation of signalling downstream of IRc and IGF-1R may aid in treatment and prevention of laminitis associated with hyperinsulinaemia., (© 2012 EVJ Ltd.)

Background: Increased blood insulin levels are associated with an increased risk of pasture-associated laminitis in equids., Objective: To determine the relationship between plasma insulin, leptin, and lipid levels, and measures of oxidative stress with adiposity in mature light breed horses., Animals: 300 randomly selected light breed horses, aged 4-20 years., Methods: 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., Results: 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., Conclusions and Clinical Importance: Maintaining horses at a BCS <7 might be important for decreasing the risk of pasture-associated laminitis., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

High glycaemic feeds are associated with the development of insulin resistance in horses. However, studies that evaluated the effect of high glycaemic feeds used horses that either ranged in body condition from lean to obese or were fed to increase body condition over a period of months; thus, the ability of high glycaemic feeds to induce insulin resistance in lean horses has not been determined. This study evaluated the insulin sensitivity of 18 lean horses fed a 10% (LO; n = 6), 20% (MED; n = 6) or 60% (HI; n = 6) non-structural carbohydrate complementary feed for 90 days. Although both the MED and HI diets increased insulinaemic responses to concentrate feeding in relation to the LO diet (p > 0.05), neither induced insulin resistance, as assessed by glucose tolerance test, following the 90-day feeding trial. Interestingly, the post-feeding suppression of plasma non-esterified fatty acids was less pronounced in HI-fed horses (p = 0.054) on days 30 and 90 of the study, potentially indicating that insulin-induced suppression of adipose tissue lipolysis was reduced. As insulin-resistant animals often have elevated plasma lipid concentrations, it is possible that altered lipid metabolism is an early event in the development of insulin resistance. The effects of high glycaemic feeds that are fed for a longer duration of time, on glucose and lipid metabolism, should be investigated further., (© 2011 Blackwell Verlag GmbH.)

Background: Obesity and hyperinsulinemia increase the risk of laminitis in horses and ponies. In mares, obesity also has been associated with increased circulating concentrations of the proinflammatory cytokine, tumor necrosis factor (TNF)-α. The association of other proinflammatory cytokines with body condition score (BCS) and insulin requires further determination., Hypothesis: Plasma concentrations of TNF, interleukin (IL)-1β, IL-6, and serum amyloid A (SAA) will positively correlate with BCS or insulin or both in horses. Furthermore, inflammatory protein concentrations will correlate with age and variables associated with BCS, including plasma insulin, triglycerides, nonesterified fatty acids, and leptin concentrations., Animals: One hundred and ten mixed light-breed horses, including mares, geldings, and stallions, aged 4-20 years., Methods: Samples were selected from a larger population of plasma samples previously collected during June-July of 2006. Samples were analyzed for TNF, IL-1β, IL-6, and SAA using commercially available ELISAs and simple correlations were used to determine relationships with BCS, insulin, age, and sex., Results: Plasma TNF (P = .047) and IL-6 (P = .021) concentrations were higher in females than males, whereas IL-6 concentrations correlated (P = .001) with age. Plasma SAA concentrations correlated with both insulin (P < .001) and BCS (P = .007)., Conclusions and Clinical Importance: This study provides evidence for factors, including age and sex, that may be associated with plasma concentrations of inflammatory proteins. Concentrations of SAA correlated with BCS and insulin, independent of age or sex. Because BCS and insulin correlate with increased SAA, it is possible that SAA is a component of laminitis pathophysiology., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Background: The prevalence of obesity in horses in the eastern United States is not well documented., Objective: To determine body condition and risk factors for obesity in horses in Southwest Virginia during summer., Animals: 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., Methods: 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)., Results: 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., Conclusions and Clinical Importance: 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., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Understanding the mechanisms involved in the development of insulin resistance in horses should enable development of effective treatment and prevention strategies. Current knowledge of these mechanisms is based upon research in obese humans and rodents, in which there is evidence that the increased production of pro-inflammatory cytokines by adipose tissue negatively influences insulin signaling in insulin-responsive tissues. In horses, plasma concentrations of the cytokine, tumor necrosis factor-α, have been positively correlated with body fatness and insulin resistance, leading to the hypothesis that inflammation may reduce insulin sensitivity in horses. However, little evidence has documented a tissue site of production and a direct link between inflammation and induction of insulin resistance has not been established. Several mechanisms are reviewed in this article, including the potential for macrophage infiltration, hyperinsulinemia, hypoxia, and lipopolysaccharide to increase pro-inflammatory cytokine production by adipose tissue of obese horses. Clearly defining the role of cytokines in reduced insulin sensitivity of horses will be a very important step in determining how obesity and insulin resistance are related.

In nonruminant herbivores, microbially derived AA could contribute to whole-body AA homeostasis and thus decrease predicted AA requirements. However, postileal capacity of AA uptake is currently unknown. Therefore, to test the hypothesis that Lys is transported across the large colon mucosal apical membrane with capacity similar to that of the small intestinal mucosa in the pony and pig, we examined Lys transport in vitro using brush border membrane vesicles (BBMV). Mucosa was collected from the distal jejunum (DJ) and proximal large colon (PLC) of growing pigs (n = 3) and ponies (n = 4), flash frozen in liquid nitrogen, and stored at -80°C. Jejunal and colonic BBMV were manufactured by Mg(2+) precipitation and used to determine initial rates and kinetics [the maximal transport rate (V(max)) and the Michaelis constant (K(M))] of l-Lys transport into apical epithelia by rapid filtration technique in Na(+)-gradient incubation buffer. Initial rates of total l-Lys uptake did not differ between the PLC and DJ in either the pig or the pony, or between the pony and the pig, at each l-Lys concentration. In the pig, compared with the DJ, l-Lys transport V(max) in the PLC did not differ (121 ± 26 and 180 ± 26 pmol•mg of protein(-1)•s(-1), respectively; P = 0.14) and l-Lys K(M) in the PLC tended to be greater (0.23 ± 0.22 and 0.89 ± 0.22 mM, respectively; P = 0.09). In the pony, compared with the DJ, l-Lys transport V(max) in the PLC was greater (62 ± 25 and 149 ± 25 pmol•mg of protein(-1)•s(-1), respectively; P = 0.04) and l-Lys K(M) in the PLC was greater (0.08 ± 0.22 and 1.05 ± 0.22 mM, respectively; P = 0.02). l-Lysine diffusion was not different between segments; however, total intestinal diffusion was greater (P = 0.03) in the pony than in the pig (115 ± 10 and 73 ± 10 pmol·mg of protein(-1)•s(-1), respectively). These results demonstrate that the large colon is capable of l-Lys transport across the apical epithelial membrane with greater capacity and less affinity than the jejunum, indicating that the large colon may play a significant role in l-Lys absorption and homeostasis in hindgut fermenters.

Equine metabolic syndrome (EMS) is a condition of obese horses characterized by insulin resistance, systemic inflammation, and an increased risk of laminitis. The pathogenesis of EMS is thought, in part, to be due to inflammatory proteins produced by adipose tissue. Reducing inflammation may decrease the incidence of laminitis in horses with EMS. Pioglitazone hydrochloride, a thiazolidinedione, has efficacy to reduce obesity associated inflammation in humans. Eight normal, adult, horses were administered 1mg/kg pioglitazone for 14 days, and eight horses served as controls. Physical examination and hematologic variables, transcript abundance of pro-inflammatory cytokines in skeletal muscle and adipose tissue, and circulating concentrations of the acute phase protein, serum amyloid A and pro-inflammatory cytokine, TNF-α were assessed prior to, and following, an LPS infusion (35 ng/kg). The objective was to determine if pre-treatment with pioglitazone would mitigate the development of inflammation and associated clinical markers of inflammation following LPS administration. Lipopolysaccharide administration induced systemic inflammation, as assessed by clinical and hematological aberrations, increased TNF-α, SAA and adipose tissue IL-6 mRNA abundance, however no mitigating effects of pioglitazone were detected. A longer treatment period or higher dose might be indicated for future experiments., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Laminitis is a painful, inflammatory disease of the equine hoof that often results in euthanasia. Elevated plasma insulin concentrations are a predictive factor for laminitis, and in previously healthy horses and ponies, laminitis was induced by infusion of insulin. Thus, we chose to determine if an infusion of insulin would increase plasma concentrations of inflammatory cytokines and cytokine mRNA abundance in subcutaneous adipose tissue, skeletal muscle, and white blood cells. Ten mature Thoroughbred mares received an insulin infusion that elevated plasma insulin concentrations for 6h or an equivalent volume of isotonic saline in a switchback design. Insulin infusion altered plasma concentrations of both TNF (P=0.037) and IL-6 (P=0.044), but did not result in consistent changes to either skeletal muscle or adipose tissue cytokine mRNA. Insulin may be involved in the production of inflammatory cytokines, and this could be a mechanism for insulin increasing the risk of laminitis., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Pioglitazone is a thiazolidinedione class of antidiabetic agent with proven efficacy in increasing insulin sensitivity in humans with noninsulin-dependent diabetes mellitus, a syndrome of insulin resistance sharing similarities with equine metabolic syndrome. The purpose of this study was to determine the pharmacokinetics of pioglitazone in adult horses following multiple oral dose administration. Pioglitazone hydrochloride (1 mg/kg) was administered orally for 11 doses at 24-h intervals, and plasma samples were collected. Initially, a pilot study was performed using one horse; and thereafter the drug was administered to six horses. Samples were analyzed by liquid chromatography with tandem mass spectrometry, and pharmacokinetic parameters were calculated using noncompartmental modeling. The maximum plasma concentration was 509.1 ± 413.5 ng/mL achieved at 1.88 ± 1.39 h following oral administration of the first dose, and 448.1 ± 303.5 ng/mL achieved at 2.83 ± 1.81 h (mean ± SD) following the eleventh dose. Apparent elimination half-life was 9.94 ± 4.57 and 9.63 ± 5.33 h after the first and eleventh dose, respectively. This study showed that in healthy horses, pioglitazone administered at a daily oral dose of 1 mg/kg results in plasma concentrations and total drug exposure approximating, but slightly below, those considered therapeutic in humans., (© 2010 Blackwell Publishing Ltd.)

Objective: To characterize the effects of pregnancy on insulin sensitivity (SI) and glucose dynamics in pasture-maintained mares fed supplemental feeds of differing energy composition., Animals: Pregnant (n = 22) and nonpregnant (10) healthy Thoroughbred mares., Procedures: Pregnant and nonpregnant mares underwent frequently sampled intravenous glucose tolerance tests at 2 times (period 1, 25 to 31 weeks of gestation; period 2, 47 weeks of gestation). Following period 1 measurements, mares were provided a high-starch (HS; 39% starch) or high-fat and -fiber (14% fat and 70% fiber) supplemental feed. From a subset of mares (n = 12), blood samples were collected hourly for 24 hours to assess glycemic and insulinemic response to feeding while pastured. The minimal model of glucose and insulin dynamics was used to estimate SI, glucose effectiveness, and acute insulin response to glucose from tolerance testing data., Results: Pregnant mares during period 1 had a lower SI and glucose effectiveness and higher acute insulin response to glucose than did nonpregnant mares. The SI value decreased in nonpregnant but not pregnant mares from periods 1 to 2. Pregnant mares fed HS feed had a greater glycemic and insulinemic response to feeding than did any other group., Conclusions and Clinical Relevance: Pregnant mares had slower glucose clearance and greater insulin secretion at 28 weeks of gestation than did nonpregnant mares. Glucose and insulin responses to meal feeding, particularly with HS feed, were greater in pregnant mares, indicating that pregnancy enhanced the postprandial glycemic and insulinemic effects of starch-rich feed supplements.

Plasma insulin concentrations are elevated (hyperinsulinemia) in horses with obesity-associated insulin resistance. In other species, insulin resistance is partly due to reduced levels of insulin receptor and the insulin-sensitive glucose transporter, and, in vitro, chronic hyperinsulinemic conditions reduce the expression of these proteins. Consumption of grain-based concentrate feeds results in postprandial hyperinsulinemia in horses, and adaptation to these diets is associated with insulin resistance. As such, it is possible that the repeated, chronic postprandial hyperinsulinemia associated with these diets could contribute to the development of insulin resistance. The purpose of the current study was to investigate the influence of a 6-h insulin infusion that increased plasma insulin concentrations to >1,000 mIU/L, on the expression of insulin receptor and glucose and lipid transporters in skeletal muscle and adipose tissue of lean, insulin-sensitive horses. Insulin infusion decreased transcript abundance of the glucose transporter 4 (P<0.05), glucose transporter 1 (GLUT1; P<0.09), and the insulin receptor (P<0.001) in adipose tissue, while increasing transcript abundance of GLUT1 (P<0.09) and decreasing protein abundance of the insulin receptor (P<0.09) in skeletal muscle. The acute, 6 hyperinsulinemic conditions achieved in this experiment resulted in alterations to mechanisms of glucose transport that could promote insulin resistance via reduced insulin-stimulated glucose disposal. Insulin infusion also reduced transcript abundance of the lipid transporters CD36 (P<0.001) and fatty acid transporter protein (FATP; P<0.05) in adipose tissue while increasing FATP (P<0.05) and lipoprotein lipase (P<0.01) in skeletal muscle. The reduction in adipose tissue lipid transporters could have been due to the decreased plasma lipid concentrations, whereas the increase in skeletal muscle may indicate that insulin stimulates lipid uptake into equine skeletal muscle. This report provides preliminary evidence that severe hyperinsulinemia alters glucose and lipid transporter expression that could promote an insulin-resistant state; these should be further investigated in horses consuming grain-based concentrates., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To investigate the effects of a continuous rate infusion (CRI) of dextrose solution or dextrose solution and insulin on glucose and insulin concentrations in healthy and endotoxin-exposed horses., Animals: 9 adult mares., Procedures: During phase 1, treatments consisted of saline (0.9% NaCl) solution (control group; n = 4) or 20% dextrose solution (group 1; 4) administered IV as a 360-minute CRI. During phase 2, treatments consisted of 360-minute CRIs of 20% dextrose solution and insulin administered simultaneously at 367.6 mg/kg/h (30 kcal/kg/d) and 0.07 U/kg/h, respectively, in healthy horses (group 2; n = 4) or horses administered 35 ng of lipopolysaccharide/kg, IV, 24 hours before starting the dextrose solution and insulin CRIs (group 3; 4). A balanced crossover study design was used in both phases. Blood samples were collected for measurement of plasma glucose and insulin concentrations., Results: Infusion of dextrose solution alone resulted in hyperglycemia for most of the 360-minute CRI. Insulin concentration increased significantly in group 1, compared with that in the control group. Mean insulin concentration of group 2 was significantly higher throughout most of the infusion period, compared with concentrations of the control group and group 1. Mean glucose concentration did not differ significantly between groups 2 and 3., Conclusions and Clinical Relevance: Insulin infusion at a rate of 0.07 U/kg/h was found to be effective for the prevention of hyperglycemia when administered concurrently with dextrose solution. This rate was considered to be safe because horses did not become hypoglycemic during infusions of dextrose solution.

Background: Obesity and insulin resistance increase the risk of laminitis in horses. Pioglitazone (PG) is an insulin-sensitizing drug used in humans that is absorbed after oral administration to horses., Hypothesis: PG treatment will increase insulin sensitivity and transcript abundance of glucose and lipid transporters in adipose and skeletal muscle tissues., Animals: Sixteen lean, healthy horses., Methods: Eight horses were administered PG (1 mg/kg bodyweight PO) for 12 days before induction of insulin resistance through IV administration of lipopolysaccharide (LPS). Treated and untreated controls (CN; n = 8) were subjected to testing of peripheral insulin sensitivity and biopsies of both subcutaneous (nuchal ligament) adipose tissue and skeletal muscle before and after treatment, and 24 hours after LPS administration., Results: PG treatment did not improve basal insulin sensitivity (CNs: 1.4 ± 0.3, PG-treated: 1.9 ± 1.3; P > .4) or mitigate LPS-induced insulin resistance (CNs: 0.4 ± 0.3, PG-treated: 0.4 ± 0.3); however, transcript abundance of glucose and lipid transporters was altered in both skeletal muscle and subcutaneous adipose tissue., Conclusions and Clinical Importance: Either a higher dose or longer treatment period might be required for physiological effects to be observed. PG is a novel therapeutic agent requiring further investigation in horses in order to determine treatment efficacy., (Copyright © 2011 by the American College of Veterinary Internal Medicine.)

Objective: To determine the effect of refeeding following an 18-hour period of feed withholding on the phosphorylation of translation initiation factors in the skeletal muscle of mature horses., Animals: 8 adult horses., Procedures: Following an 18-hour period of feed withholding, horses either continued to have feed withheld (postabsorptive state) or were fed 2 g/kg of a high-protein feed (33% crude protein) at time 0 and 30 minutes (postprandial state). Blood samples were taken throughout the experimental period. At 90 minutes, a biopsy specimen was taken from the middle gluteal muscle to measure the phosphorylation of translation initiation factors and tissue amino acid concentrations. Plasma glucose, insulin, and amino acid concentrations were also measured., Results: Horses in the postprandial state had significantly higher plasma insulin, glucose, and amino acid concentrations than did those in the postabsorptive state at the time of biopsy. Refeeding significantly increased the phosphorylation state of riboprotein S6 and eukaryotic initiation factor 4E binding protein 1., Conclusions and Clinical Relevance: In mature horses, feeding resulted in increased mammalian target of rapamycin signaling and the mechanism appeared to be independent of an increase in Akt phosphorylation at Ser⁴⁷³. Results indicate that adult horses may be able to increase rates of muscle protein synthesis in response to feeding and that dietary amino acids appear to be the main mediators of this effect.

Obesity and insulin resistance are risk factors for laminitis in horses and ponies, and diet can play an important role in modulating these risk factors. Dietary supplementation with prebiotic fibers, such as short-chain fructo-oligosaccharides (scFOS), has resulted in improvement of insulin sensitivity in obese dogs and rodents. Thus, we hypothesized that scFOS may reduce insulin resistance in obese horses and designed a study to evaluate the effect of dietary supplementation with scFOS on insulin sensitivity. Eight mature Arabian geldings (BW = 523.0 ± 56.5 kg) with an average BCS of 8 were included in a crossover study. In each period, 4 horses were provided 45 g/d per horse of maltodextrin (control) and 4 horses received the same amount of scFOS for 6 wk, with a 3-wk washout between periods. Resting plasma concentrations of glucose, insulin, triglycerides, and leptin were measured. Minimal model analysis of a frequently sampled intravenous glucose tolerance test was used to evaluate insulin sensitivity, glucose effectiveness, acute insulin response to glucose, and disposition index. Without affecting BW and BCS, dietary supplementation with scFOS increased (P < 0.05) insulin sensitivity and reduced (P < 0.05) acute insulin response to glucose in comparison with maltodextrin but did not alter (P > 0.05) glucose effectiveness and disposition index. Resting serum insulin concentration also was reduced (P < 0.05) by scFOS supplementation but not by maltodextrin (P > 0.05). There was no effect (P > 0.05) of scFOS supplementation on plasma glucose or serum triglyceride and leptin concentrations. This study demonstrated that scFOS can moderately improve insulin sensitivity of obese horses, a finding that has potential relevance to the dietary management of obese, insulin-resistant horses at increased risk for laminitis.

Reasons for Performing Study: Tools and criteria to evaluate and understand glucose metabolism are essential to optimise equine energy utilisation for exercise performance and reduced metabolic health risks., Objectives: To re-evaluate models of glucose kinetics in the horse at rest and during endurance type exercise using a single injection technique and compartmental modelling., Methods: Twelve exercise trained Arabian geldings received a bolus of 100 µmol/kg bwt [6,6-(2) H]glucose i.v. while at rest and while running at ∼ 4 m/s on a treadmill. Tracer and tracee glucose curves from 4-150 min after the bolus dose (while the subject maintained its resting or exercising state) were described by a 2 term exponential decay curve. Compartmental modelling was performed simultaneously for each horse's resting and exercise curves using an 'exercise effect' parameter for each compartmental exchange rate during exercise., Results: Exercise increased all rate constants and transport flows for glucose between compartments by 110-145% (P ≤ 0.004). Total glucose transport through the system increased from 8.9 ± 0.6 µmol/min/kg/bwt at rest to 25.0 ± 1.1 µmol/min/kg bwt during exercise (P < 0.001). Exercise decreased the volume of the primary glucose compartment by 8% (P = 0.006) and increased plasma glucose clearance rate by almost 200% (P < 0.001). Turnover times and mean residence times were decreased approximately 60% by exercise (P < 0.001), whilst turnover rates were increased 125% (P < 0.001)., Conclusions: Single-injection tracer kinetics and compartmental modelling represent a valuable tool to quantify tracee availability to and use by tissue., Potential Relevance: This technique could represent a beneficial tool for future studies exploring the role of glucose metabolism in equine exercise performance and metabolic disease., (© 2010 EVJ Ltd.)

Reasons for Performing Study: There is evidence that extensive training in cool conditions results in improvements to heat dissipation that contribute to successful acclimatisation. In horses, the effects of a less extensive training regimen have not been determined., Objective: This study investigated whether 10 consecutive days of moderate intensity treadmill training in cool conditions would improve thermoregulatory and sweating responses of horses to exercise in the heat., Methods: Six unfit Thoroughbred horses completed a standardised treadmill exercise test (SET) in hot, dry conditions (32-34 °C, 45-55% RH) before (SET1) and after (SET2) 10 consecutive days of running at 55% VO2max for 60 min in cool conditions (19-21°C, 45-55% RH). Each SET consisted of a 5 min warm-up and cool down at a walk, 40 min of trotting (50% VO2max), 7 min at 75% VO2max and a 30 min standing recovery. Bodyweight was determined pre- and post SET. Heart rate, rectal, skin, pulmonary artery and muscle temperatures were measured throughout the SETs and sweating rate (SR) and sweat ion losses determined for each 5 min interval., Results: Following training, mean VO2max increased by 8.9% (P < 0.05). In SET2, PCV was lower during the last 30 min of exercise and end-exercise rectal, muscle and pulmonary artery temperatures were decreased by 1.5 ± 0.2, 0.8 ± 0.1 and 1.0 ± 0.2 °C, respectively (P < 0.05). Peak SR and the pattern of sweat ion losses during exercise was unchanged post training whereas SR and sweat losses during recovery were decreased (P < 0.05)., Conclusions: Similar SRs for a given core temperature during exercise but a more rapid decrease in recovery resulted in an overall reduction in sweat fluid losses with no change in sweat ion losses after training., Relevance: The results provide insight into the extent to which short-term training can improve the capacity of horses to exercise in hot conditions., (© 2010 EVJ Ltd.)

Reasons for Performing Study: There is limited information about factors regulating glucose utilisation post exercise in horses., Objectives: To determine the effects of a single bout of moderate intensity exercise on measures of insulin-mediated (IMGU) and noninsulin-mediated (NIMGU) glucose uptake during a hyperglycaemic clamp (HC)., Methods: Hyperglycaemic clamps were administered in random order to 8 Standardbreds under 4 conditions: 1) rest, insulinopenia (R-L); 2) rest, hyperinsulinaemia (R-H); 3) post exercise (45 min at ∼ 50% VO2peak), insulinopenia (Ex-L) and 4) post exercise, hyperinsulinaemia (Ex-H). In the R-L and Ex-L trials, somatostatin was infused to suppress insulin secretion and induce insulinopenia. After 30 min, a 2 h HC was initiated with plasma glucose concentrations maintained at ∼ 10 mmol/l by variable glucose infusion. In R-H and Ex-H, regular insulin (1.0 mu/kg bwt/min) was also administered to induce physiological hyperinsulinaemia. Serum insulin and C-peptide concentrations were measured in samples obtained at 10 min intervals. Glucose uptake was calculated from mean glucose infusion rate (GIR) during the last 60 min of the HC., Results: In all HCs C-peptide remained below baseline concentrations, evidence of suppression of insulin secretion by somatostatin. Overall, mean ± s.e. insulin concentrations during the final 60 min of the HC in R-L and Ex-L were 5.7 ± 1.1 and 6.9 ± 1.9 mu/l respectively, and corresponding values in R-H and Ex-H were 64.1 ± 11.1 and 61.2 ± 10.9 mu/l. Prior exercise affected IMGU but not NIMGU. Over the final 60 min of the HC, mean GIR was higher (P < 0.001) in Ex-H (5.6 ± 1.1 mg/kg bwt/min) than in R-H (3.3 ± 0.9 mg/kg bwt/min), whereas mean GIR did not differ (P = 0.26) between R-L (1.2 ± 0.3 mg/kg bwt/min) and Ex-L (1.8 ± 0.5 mg/kg bwt/min)., Conclusions: A single bout of moderate intensity exercise increased glucose uptake during a hyperglycaemic clamp under hyperinsulinaemic conditions but not under somatostatin-induced insulinopenia., (© 2010 EVJ Ltd.)

Reasons for Performing Study: Providing protein or amino acid mixtures in combination with glucose to post exercise in man has resulted in increases in the post feeding insulin response and in muscle glycogen and protein synthesis rates. However, whether protein and/or amino acids can modify the post exercise insulin responses in horses remains to be fully elucidated., Objectives: To determine whether whey protein or leucine addition to a glucose solution affects the post gavage plasma insulin, glucose and amino acid responses in horses and whether these responses are different following a period of exercise vs. rest., Methods: Six mature, conditioned Thoroughbreds received a nasogastric gavage containing either 1 g/kg bwt glucose (G), G + 0.3 g/kg bwt whey protein (GW) or G + 0.3 g/kg bwt leucine (GL), following a period of either rest (R) or an exercise test on a high speed treadmill (EX). Each horse was studied under all 6 treatment conditions, separated by 10 day intervals. Blood samples were collected pre-exercise/rest, pregavage and at regular intervals up to 300 min post gavage. Plasma was analysed for glucose and amino acid concentrations and serum insulin concentrations were determined., Results: There was a significantly (P < 0.05) greater insulin response in GL-R and GL-EX when compared to the other treatments. When compared to rest, post exercise plasma glucose responses were lower in G and GW but unchanged following GL administration. Plasma alanine concentrations were elevated post exercise in all EX treatments. With the exception of markedly elevated plasma leucine concentrations after GL-R and GL-EX, the plasma concentrations of all indispensable amino acids decreased during the post gavage period., Conclusions: Leucine but not whey protein augmented the serum insulin response to an oral glucose load. Leucine supplementation warrants further investigation as a means to increase the rate of post exercise muscle glycogen synthesis in horses., (© 2010 EVJ Ltd.)

Reasons for Performing Study: Starch rich (S) feeds reduce insulin sensitivity in untrained horses when compared to high fat (F) feeds, but insulin sensitivity is not affected when S or F are fed during exercise training. The effects of S vs. F on training-associated alterations in skeletal muscle glucose metabolism are unknown., Objectives: To determine the effects of dietary energy source on training-associated changes in insulin sensitivity, skeletal muscle GLUT4 protein and hexokinase (HK) and glycogen synthase (GS) activities in horses., Methods: After a baseline period on an all forage diet (Phase 1), horses were adapted to high starch (S) or high fat (F) diets (n = 7/group) for 6 weeks (Phase 2) and then completed 7 weeks of exercise training (Phase 3) on the same diets. To measure insulin sensitivity (SI), minimal model analysis of a frequently-sampled i.v. glucose tolerance test was performed at the end of each phase. Middle gluteal muscle biopsies to measure GLUT-4 protein content, muscle glycogen and HK and GS activities were taken before and after euglycaemic-hyperinsulinaemic clamps administered after each phase. Data were analysed by repeated measures ANOVA., Results: In S, SI was 36% lower (P < 0.05) after Phase 2 when compared to Phase 1 but was unchanged in F. After Phase 3, SI was increased (P < 0.01) in S and F compared to Phase 2 and did not differ (P > 0.05) between diets. Middle gluteal muscle GLUT-4 protein and post clamp HK activity were increased (P < 0.05) in S after Phase 3, with higher (P < 0.01) GLUT4 in S than in F. GS activities were unchanged in both diets., Conclusions: Adaptation to S resulted in decreased SI mitigated by moderate physical conditioning. Increased GLUT-4 protein content and HK activity in S may have contributed to higher SI after training., (© 2010 EVJ Ltd.)

Epidemiologic studies indicate that most laminitis cases occur in horses and ponies kept at pasture, hence the term 'pasture-associated laminitis'. Clinical cases of laminitis most often occur under conditions that favor accumulation of rapidly fermentable nonstructural carbohydrates (fructans, simple sugars, or starches) in pasture, and animals with an equine metabolic syndrome (EMS) phenotype (insulin resistance, abnormal insulin dynamics, +/- obesity) seem to be at highest risk for developing the condition. Although the mechanisms linking consumption of pasture forage with development of lamellar failure have not been fully elucidated, a systemic inflammatory response that accompanies hindgut carbohydrate overload likely initiates lamellar inflammatory events (including infiltration and activation of leukocytes) that contribute to destruction of lamellar epithelium and extracellular matrix. This article reviews current knowledge on the epidemiology and risk factors for pasture-associated laminitis, including the role of forage carbohydrates and metabolic/endocrine predispositions, and also discusses the pathophysiology of this condition., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Background: Insulin resistance has been associated with risk of laminitis in horses. Genes coding for proinflammatory cytokines and chemokines are expressed more in visceral adipose tissue than in subcutaneous adipose tissue of insulin-resistant (IR) humans and rodents., Hypothesis/objectives: To investigate adipose depot-specific cytokine and chemokine gene expression in horses and its relationship to insulin sensitivity (SI)., Animals: Eleven light breed mares., Methods: Animals were classified as IR (SI=0.58+/-0.31x10(-4) L/min/mU; n=5) or insulin sensitive (IS; SI=2.59+/-1.21x10(-4) L/min/mU; n=6) based on results of a frequently sampled intravenous glucose tolerance test. Omental, retroperitoneal, and mesocolonic fat was collected by ventral midline celiotomy; incisional nuchal ligament and tail head adipose tissue biopsy specimens were collected concurrently. The expression of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, plasminogen activator inhibitor-1 (PAI-1), and monocyte chemoattractant protein-1 (MCP-1) in each depot was measured by real-time quantitative polymerase chain reaction. Data were analyzed by 2-way analysis of variance for repeated measures (P<.05)., Results: No differences in TNF-alpha, IL-1beta, IL-6, PAI-1, or MCP-1 mRNA concentrations were noted between IR and IS groups for each depot. Concentrations of mRNA coding for IL-1beta (P=.0005) and IL-6 (P=.004) were significantly higher in nuchal ligament adipose tissue than in other depots., Conclusions and Clinical Importance: These data suggest that the nuchal ligament depot has unique biological behavior in the horse and is more likely to adopt an inflammatory phenotype than other depots examined. Visceral fat may not contribute to the pathogenesis of obesity-related disorders in the horse as in other species.