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Article ; Online: Effect of aging on monocyte phagocytic and inflammatory functions, and on the ex vivo inflammatory responses to lipopolysaccharide, in horses.

Herbst, A C / Reedy, S E / Page, A E / Horohov, D W / Adams, A A

Veterinary immunology and immunopathology

2022 Volume 250, Page(s) 110459

Abstract: Studies investigating age-related changes in the function of monocytes are currently limited for horses. Thus, the main goal of this study was to determine the effect of aging on monocyte phagocytic capacity and pro-inflammatory cytokine responses to ... ...

Abstract	Studies investigating age-related changes in the function of monocytes are currently limited for horses. Thus, the main goal of this study was to determine the effect of aging on monocyte phagocytic capacity and pro-inflammatory cytokine responses to bacterial lipopolysaccharide (LPS). A second goal of this work was to examine the effect of aging on the inflammatory cytokine responses to LPS in a whole blood ex vivo model. Seven healthy young adult (4-6 years of age) and seven healthy senior horses (>20 years of age) were enrolled. Phagocytosis of E. coli, and pro-inflammatory cytokine (TNFα) responses to LPS, were measured in monocytes by flow cytometry. Gene expressions of pro-inflammatory cytokines (TNFα, IL-1β, IL-6, IL-8, IL-18, CCL-5, CCL-2) were measured in peripheral blood mononuclear cells (PBMCs) and whole blood by RT-qPCR post incubation for 2 h or 6 h with a low (0.01 µg/mL) or a high (1 µg/mL) dose of LPS. Two sets of statistical models were applied to compare the age groups, one adjusted, and one unadjusted for the horses' body condition scores (BCS). The percentage of monocytes that phagocytosed E. coli after 2 h of incubation was significantly lower in senior compared to young adult horses in the BCS-adjusted model. In the senior group, the expression of IL-1β in 2 h-0.01 µg/mL LPS-stimulated PBMCs was significantly higher than in the young adult group (BCS-adjusted and unadjusted models). In senior horses, expressions of IL-8 and IL-6 in whole blood samples stimulated for 6 h with 0.01 µg/mL LPS and for 2 h with 1 µg/mL LPS, respectively, were significantly lower than in young adult horses (BCS-adjusted models). The results of this study suggest that the phagocytic function of monocytes, as well as their IL-1β response to LPS may be altered in senior horses. In addition, the whole blood IL-8 and IL-6 gene expression responses to LPS may be insufficient in senior horses. While investigation of the effect of BCS on monocyte functions and whole blood pro-inflammatory LPS-responses was not a major goal of this work, it appears that adiposity may play a role in innate immune cell function, as significant differences between the age groups were often not apparent until the models were adjusted for BCS.
MeSH term(s)	Aging ; Animals ; Cytokines ; Escherichia coli ; Horses ; Interleukin-6/metabolism ; Interleukin-8/genetics ; Leukocytes, Mononuclear/metabolism ; Lipopolysaccharides/pharmacology ; Monocytes ; Tumor Necrosis Factor-alpha/genetics
Chemical Substances	Cytokines ; Interleukin-6 ; Interleukin-8 ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2022-07-12
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	754160-0
ISSN	1873-2534 ; 0165-2427
ISSN (online)	1873-2534
ISSN	0165-2427
DOI	10.1016/j.vetimm.2022.110459
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Article ; Online: Evaluation of seasonal influences on adrenocorticotropic hormone response to the thyrotropin-releasing hormone stimulation test and its accuracy for diagnosis of pituitary pars intermedia dysfunction.

Adams, A A / Siard-Altman, M H / Reedy, S E / Barker, D / Elzinga, S / Sanz, M G / Urschel, K / Ireland, J L

Veterinary journal (London, England : 1997)

2023 Volume 300-302, Page(s) 106035

Abstract: Pituitary pars intermedia dysfunction (PPID) is an age-related neurodegenerative disorder, affecting >20 % of older horses. There is a need for improved endocrine tests for early disease detection, and the thyrotropin-releasing hormone (TRH) stimulation ... ...

Abstract	Pituitary pars intermedia dysfunction (PPID) is an age-related neurodegenerative disorder, affecting >20 % of older horses. There is a need for improved endocrine tests for early disease detection, and the thyrotropin-releasing hormone (TRH) stimulation test has been recommended for diagnosis of early or mild cases. However, it is currently not recommended for year-round use due to marked seasonal variability. The aims of this cohort study were to evaluate effects of month and season on adrenocorticotropic hormone (ACTH) responses to TRH stimulation and to derive monthly cut-offs for PPID diagnosis. Sixty-three horses were assigned to control (n = 17), subclinical PPID (n = 21) and clinical PPID (n = 25) groups, based on a composite reference standard that combined clinical history and examination findings with endocrine test results. TRH stimulation tests were performed monthly for a 12-month period. Circannual changes were evaluated with one- and two-way repeated-measures analysis of variance and receiver operating characteristic curve analysis was used to derive cut-off values for basal and TRH-stimulated ACTH. TRH-stimulated ACTH concentrations were lowest in February-May and highest in August-October. Specificity of both basal and 30 min post-TRH ACTH was generally higher than sensitivity, and TRH stimulation had improved diagnostic accuracy compared to basal ACTH, although its sensitivity was not significantly greater year-round. TRH stimulation tests yielded considerably more positive results than basal ACTH in the subclinical group, but few additional positive results in clinical PPID cases. There were large differences between cut-offs that maximised sensitivity or specificity for TRH-stimulated ACTH, highlighting the importance of considering clinical presentation alongside test results in diagnostic decision-making.
MeSH term(s)	Horses ; Animals ; Adrenocorticotropic Hormone/pharmacology ; Thyrotropin-Releasing Hormone/pharmacology ; Seasons ; Cohort Studies ; Pituitary Diseases/diagnosis ; Pituitary Diseases/veterinary ; Pituitary Gland, Intermediate/metabolism ; Horse Diseases/diagnosis
Chemical Substances	Adrenocorticotropic Hormone (9002-60-2) ; Thyrotropin-Releasing Hormone (5Y5F15120W)
Language	English
Publishing date	2023-10-05
Publishing country	England
Document type	Journal Article
ZDB-ID	428614-5
ISSN	1532-2971 ; 0372-5545 ; 1090-0233
ISSN (online)	1532-2971
ISSN	0372-5545 ; 1090-0233
DOI	10.1016/j.tvjl.2023.106035
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Article ; Online: Effect of aging on monocyte phagocytic and inflammatory functions, and on the ex vivo inflammatory responses to lipopolysaccharide, in horses

Herbst, A.C. / Reedy, S.E. / Page, A.E. / Horohov, D.W. / Adams, A.A.

Veterinary Immunology and Immunopathology. 2022 Aug., v. 250 p.110459-

2022

Abstract	Studies investigating age-related changes in the function of monocytes are currently limited for horses. Thus, the main goal of this study was to determine the effect of aging on monocyte phagocytic capacity and pro-inflammatory cytokine responses to bacterial lipopolysaccharide (LPS). A second goal of this work was to examine the effect of aging on the inflammatory cytokine responses to LPS in a whole blood ex vivo model. Seven healthy young adult (4–6 years of age) and seven healthy senior horses (>20 years of age) were enrolled. Phagocytosis of E. coli, and pro-inflammatory cytokine (TNFα) responses to LPS, were measured in monocytes by flow cytometry. Gene expressions of pro-inflammatory cytokines (TNFα, IL-1β, IL-6, IL-8, IL-18, CCL-5, CCL-2) were measured in peripheral blood mononuclear cells (PBMCs) and whole blood by RT-qPCR post incubation for 2 h or 6 h with a low (0.01 µg/mL) or a high (1 µg/mL) dose of LPS. Two sets of statistical models were applied to compare the age groups, one adjusted, and one unadjusted for the horses’ body condition scores (BCS). The percentage of monocytes that phagocytosed E. coli after 2 h of incubation was significantly lower in senior compared to young adult horses in the BCS-adjusted model. In the senior group, the expression of IL-1β in 2 h-0.01 µg/mL LPS-stimulated PBMCs was significantly higher than in the young adult group (BCS-adjusted and unadjusted models). In senior horses, expressions of IL-8 and IL-6 in whole blood samples stimulated for 6 h with 0.01 µg/mL LPS and for 2 h with 1 µg/mL LPS, respectively, were significantly lower than in young adult horses (BCS-adjusted models). The results of this study suggest that the phagocytic function of monocytes, as well as their IL-1β response to LPS may be altered in senior horses. In addition, the whole blood IL-8 and IL-6 gene expression responses to LPS may be insufficient in senior horses. While investigation of the effect of BCS on monocyte functions and whole blood pro-inflammatory LPS-responses was not a major goal of this work, it appears that adiposity may play a role in innate immune cell function, as significant differences between the age groups were often not apparent until the models were adjusted for BCS.
Keywords	Escherichia coli ; adiposity ; body condition ; ex vivo studies ; flow cytometry ; gene expression ; genes ; immunopathology ; interleukin-18 ; interleukin-6 ; interleukin-8 ; lipopolysaccharides ; models ; monocytes ; phagocytosis ; young adults ; Horse ; Aging ; Monocyte ; Inflammation ; Innate immunity
Language	English
Dates of publication	2022-08
Publishing place	Elsevier B.V.
Document type	Article ; Online
ZDB-ID	754160-0
ISSN	1873-2534 ; 0165-2427
ISSN (online)	1873-2534
ISSN	0165-2427
DOI	10.1016/j.vetimm.2022.110459
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Article ; Online: Interaction between anthelmintic treatment and vaccine responses in ponies naturally infected with cyathostomins.

Nielsen, M K / Rubinson, E F / Chambers, T M / Horohov, D W / Wagner, B / Betancourt, A / Reedy, S E / Jacobsen, S

Veterinary immunology and immunopathology

2015 Volume 164, Issue 3-4, Page(s) 110–117

Abstract: Anthelmintics and vaccines are commonly given concurrently in routine equine management, but it is unknown to what extent an interaction between the two exists. Cyathostomins can modulate the local immune response by stimulating a type 2 helper T cell ( ... ...

Abstract	Anthelmintics and vaccines are commonly given concurrently in routine equine management, but it is unknown to what extent an interaction between the two exists. Cyathostomins can modulate the local immune response by stimulating a type 2 helper T cell (Th2) response. In addition, anti-inflammatory effects of ivermectin have been found in rodent models. It is unknown whether these anti-inflammatory effects affect the acute phase response elicited by commonly used vaccines. This study evaluated how the acute phase inflammatory response, leukocyte expression of pro-inflammatory cytokines, and vaccine-specific titers induced by simultaneous injection of three vaccines (West Nile Virus, Equine Herpes Rhinopneumonitis, and Keyhole Limpet Hemocyanin) were modulated by concurrent administration of ivermectin or pyrantel pamoate in ponies naturally infected with cyathostomins. Mixed-breed yearling ponies were blocked by gender and fecal strongyle egg count, then randomly assigned to three treatment groups: ivermectin (n=8), pyrantel pamoate (n=8), and control (n=7). All ponies received vaccinations intramuscularly on days 0 and 29, and anthelmintics were administered on the same days. Whole blood, serum and plasma samples were collected one, three and 14 days after each vaccination. Samples were analyzed for concentrations of acute phase reactants (haptoglobin, serum amyloid A, fibrinogen and iron), mRNA expression levels of cytokines (interleukin (IL)-1β, IL-4, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ) in leukocytes, and vaccine-specific antibody titers. A marked acute-phase response was noted following both vaccinations. In contrast, the pattern of change in cytokine expression was less pronounced and more variable. Statistical differences were observed between groups for haptoglobin, fibrinogen, IL-1β, IL-4, and IL-10, but differences were generally small and none of the vaccine titers were different between the groups. Taken together, the study found some signs of modulation of immunologic or inflammatory responses to the administered vaccines, when anthelmintics were administered concurrently, but these are unlikely to have practical implications for vaccination routines.
MeSH term(s)	Animals ; Anthelmintics/therapeutic use ; Cytokines/analysis ; Female ; Horses ; Immunoglobulin G/blood ; Male ; Strongyle Infections, Equine/drug therapy ; Strongyle Infections, Equine/immunology ; Vaccination ; Vaccines/immunology
Chemical Substances	Anthelmintics ; Cytokines ; Immunoglobulin G ; Vaccines
Language	English
Publishing date	2015-04-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	754160-0
ISSN	1873-2534 ; 0165-2427
ISSN (online)	1873-2534
ISSN	0165-2427
DOI	10.1016/j.vetimm.2015.01.009
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Article: Effect of short-term exercise training on insulin sensitivity in obese and lean mares.

Powell, D M / Reedy, S E / Sessions, D R / Fitzgerald, B P

Equine veterinary journal. Supplement

2002 , Issue 34, Page(s) 81–84

Abstract: Twelve untrained aged mares were used to determine whether 7 days of light exercise improved peripheral tissue insulin sensitivity. Mares were divided into obese-exercised (n = 3), obese-sedentary (n = 3), lean-exercised (n = 3) and lean-sedentary (n = 3) ...

Abstract	Twelve untrained aged mares were used to determine whether 7 days of light exercise improved peripheral tissue insulin sensitivity. Mares were divided into obese-exercised (n = 3), obese-sedentary (n = 3), lean-exercised (n = 3) and lean-sedentary (n = 3) groups. The exercised groups were worked at a trot to a heart rate (HR) of not more than 140 beats/min for 30 min in a round pen. Each group was subjected to 3 euglycaemic hyperinsulinaemic clamps: prior to exercise (P), 24 h following the seventh exercise training session (E) and 9 days postexercise training (PE). Prior to exercise training, the mares in the obese group were confirmed insulin-resistant compared to the mares in the lean group. There was no change in bodyweight or body condition in the obese or lean groups throughout the study. Glucose infusion rate (GIR) was higher (P<0.05) on E compared to P days in the obese-exercised and lean-exercised groups. Insulin sensitivity returned to pre-exercise values by 9 days postexercise in the obese-exercised and lean-exercised groups. The results of this study suggest that improvement in insulin sensitivity occurs in obese mares without a long interval of exercise training and in the absence of a change in bodyweight.
MeSH term(s)	Animals ; Female ; Glucose/metabolism ; Glucose Clamp Technique/veterinary ; Horse Diseases/blood ; Horse Diseases/metabolism ; Horses ; Insulin/blood ; Insulin Resistance/physiology ; Obesity/blood ; Obesity/metabolism ; Obesity/veterinary ; Physical Conditioning, Animal/physiology ; Random Allocation
Chemical Substances	Insulin ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2002-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
DOI	10.1111/j.2042-3306.2002.tb05396.x
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Article: Development of a model for inducing transient insulin resistance in the mare: preliminary implications regarding the estrous cycle.

Sessions, D R / Reedy, S E / Vick, M M / Murphy, B A / Fitzgerald, B P

Journal of animal science

2004 Volume 82, Issue 8, Page(s) 2321–2328

Abstract: Peripheral insulin resistance is the failure of proper cellular glucose uptake in response to insulin. Insulin resistance and hyperinsulinemia are associated with several disease states in the horse and reproductive function disturbances in humans, ... ...

Abstract	Peripheral insulin resistance is the failure of proper cellular glucose uptake in response to insulin. Insulin resistance and hyperinsulinemia are associated with several disease states in the horse and reproductive function disturbances in humans, including polycystic ovarian syndrome. To test the hypothesis that insulin resistance (IR) and hyperinsulinemia disrupt the estrous cycle in mares, two experiments were conducted to first develop a model to induce IR and to then examine the effect of this model on the duration of the estrous cycle. In Exp. 1, a hyperinsulinemic-euglycemic clamp (HEC) procedure was performed on seven mares to determine insulin sensitivity before and immediately following infusion of a heparinized lipid solution. The HEC procedure was repeated 1 wk after lipid infusion. Mares developed IR following the lipid infusion (P < 0.05), and some individuals maintained IR for up to 1 wk. Mares also exhibited increased blood insulin both immediately following treatment and 1 wk later (P < 0.05). In Exp. 2, induction of insulin resistance by lipid solution was not accompanied by changes in circulating concentrations of luteinizing hormone, and duration of the luteal phase, compared with the duration of untreated luteal phases. Nonetheless, lipid infusion and the resultant insulin resistance were associated with an increased interovulatory period (P < 0.05), and peak concentrations of progesterone (P < 0.05) were higher during the treated vs. untreated luteal phases of the estrous cycle. The results from the preliminary study suggest that infusion of a lipid solution may induce transient insulin resistance and hyperinsulinemia. The resulting insulin resistance and hyperinsulinemia may modify characteristics of the estrous cycle, perhaps at the level of the ovary.
MeSH term(s)	Animals ; Disease Models, Animal ; Estrus/drug effects ; Estrus/physiology ; Fatty Acids, Nonesterified/blood ; Female ; Glucose/administration & dosage ; Glucose Clamp Technique/veterinary ; Horse Diseases/physiopathology ; Horses/blood ; Horses/physiology ; Hyperinsulinism/physiopathology ; Hyperinsulinism/veterinary ; Infusions, Intravenous/veterinary ; Insulin/blood ; Insulin Resistance ; Lipids/administration & dosage ; Lipids/pharmacology ; Luteal Phase/drug effects ; Luteal Phase/physiology ; Luteinizing Hormone/blood ; Ovulation/drug effects ; Ovulation/physiology ; Progesterone/blood ; Time Factors
Chemical Substances	Fatty Acids, Nonesterified ; Insulin ; Lipids ; Progesterone (4G7DS2Q64Y) ; Luteinizing Hormone (9002-67-9) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2004-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	390959-1
ISSN	1525-3163 ; 0021-8812
ISSN (online)	1525-3163
ISSN	0021-8812
DOI	10.2527/2004.8282321x
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Article: Effects of systemic inflammation on insulin sensitivity in horses and inflammatory cytokine expression in adipose tissue

Vick, M.M / Murphy, B.A / Sessions, D.R / Reedy, S.E / Kennedy, E.L / Horohov, D.W / Cook, R.F / Fitzgerald, B.P

American journal of veterinary research. 2008 Jan., v. 69, no. 1

2008

Keywords	horse diseases ; inflammation ; insulin resistance ; cytokines ; adipose tissue ; mares ; lipopolysaccharides ; blood chemistry ; adipocytes ; interleukin-1 ; interleukin-6 ; tumor necrosis factor-alpha ; gene expression ; reverse transcriptase polymerase chain reaction
Language	English
Dates of publication	2008-01
Size	p. 130-139.
Document type	Article
ZDB-ID	390796-x
ISSN	1943-5681 ; 0002-9645
ISSN (online)	1943-5681
ISSN	0002-9645
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Article: Development of a model for inducing transient insulin resistance in the mare: preliminary implications regarding the estrous cycle

Sessions, D.R / Reedy, S.E / Vick, M.M / Murphy, B.A / Fitzgerald, B.P

Journal of animal science. 2004 Aug., v. 82, no. 8

2004

Abstract	Peripheral insulin resistance is the failure of proper cellular glucose uptake in response to insulin. Insulin resistance and hyperinsulinemia are associated with several disease states in the horse and reproductive function disturbances in humans, including polycystic ovarian syndrome. To test the hypothesis that insulin resistance (IR) and hyperinsulinemia disrupt the estrous cycle in mares, two experiments were conducted to first develop a model to induce IR and to then examine the effect of this model on the duration of the estrous cycle. In Exp. 1, a hyperinsulinemic-eug-lycemic clamp (HEC) procedure was performed on seven mares to determine insulin sensitivity before and immediately following infusion of a heparinized lipid solution. The HEC procedure was repeated 1 wk after lipid infusion. Mares developed IR following the lipid infusion (P < 0.05), and some individuals maintained IR for up to 1 wk. Mares also exhibited increased blood insulin both immediately following treatment and 1 wk later (P < 0.05). In Exp. 2, induction of insulin resistance by lipid solution was not accompanied by changes in circulating concentrations of luteinizing hormone, and duration of the luteal phase, compared with the duration of untreated luteal phases. Nonetheless, lipid infusion and the resultant insulin resistance were associated with an increased interovulatory period (P < 0.05), and peak concentrations of progesterone (P < 0.05) were higher during the treated vs. untreated luteal phases of the estrous cycle. The results from the preliminary study suggest that infusion of a lipid solution may induce transient insulin resistance and hyperinsulinemia. The resulting insulin resistance and hyperinsulinemia may modify characteristics of the estrous cycle, perhaps at the level of the ovary.
Keywords	insulin resistance ; free fatty acids ; insulin ; mares ; estrous cycle ; hyperinsulinemia ; lipid metabolism ; blood chemistry ; luteinizing hormone ; corpus luteum ; preovulatory period ; progesterone ; hormone secretion ; glucose ; ovulation ; ovarian follicles ; hormonal regulation
Language	English
Dates of publication	2004-08
Size	p. 2321-2328.
Document type	Article
ZDB-ID	390959-1
ISSN	1525-3163 ; 0021-8812
ISSN (online)	1525-3163
ISSN	0021-8812
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Article: Potential signals mediating the maintenance of reproductive activity during the non-breeding season of the mare.

Fitzgerald, B P / Reedy, S E / Sessions, D R / Powell, D M / McManus, C J

Reproduction (Cambridge, England) Supplement

2002 Volume 59, Page(s) 115–129

Abstract: The seasonal nature of reproductive activity in mares is widely accepted and considerable attention has focused on the mechanisms that lead to the initiation of the breeding season. In contrast, considerably less information is available about the ... ...

Abstract	The seasonal nature of reproductive activity in mares is widely accepted and considerable attention has focused on the mechanisms that lead to the initiation of the breeding season. In contrast, considerably less information is available about the termination of the breeding season. It is interesting to note that each winter a sub-population of mares continues to undergo oestrous cyclicity during the non-breeding season. Continuation of reproductive activity during the winter occurs most frequently in mares that maintain a non-pregnant condition in successive years. The maintenance of a non-pregnant condition in successive years leads to an increase in the percentage of total body fat and it has been proposed that the degree of adiposity may be a determinant of reproductive activity during the winter months. To investigate this hypothesis we have manipulated fat stores by either pharmacological treatments or feed restriction. The studies described in this review demonstrate that manipulation of body fat during the autumn months fails to modify the mechanisms that lead to anoestrus or the proportion of mares that continues to show oestrous cyclicity during the winter months. On the basis of these and related studies two hypotheses are presented that may serve as a template for future work. The first hypothesis proposes that one aspect of the long-term regulation of seasonal reproductive rhythms in mares, specifically anoestrus, may reflect recognition of the availability of metabolic fuels before perception of a change in photoperiod. Alternatively, energy availability may need to reach a critical value before a presumptive inhibitory daylength signal initiates termination of the breeding season. This review describes previous and current studies that have led to development of these proposals.
MeSH term(s)	Adipose Tissue/metabolism ; Adrenergic beta-Agonists/pharmacology ; Anestrus/drug effects ; Anestrus/physiology ; Animal Nutritional Physiological Phenomena ; Animals ; Body Composition/physiology ; Breeding ; Clenbuterol/pharmacology ; Female ; Horses/physiology ; Humans ; Insulin/physiology ; Leptin/pharmacology ; Recombinant Proteins/pharmacology ; Seasons
Chemical Substances	Adrenergic beta-Agonists ; Insulin ; Leptin ; Recombinant Proteins ; Clenbuterol (XTZ6AXU7KN)
Language	English
Publishing date	2002
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1477-0415 ; 0449-3087
ISSN	1477-0415 ; 0449-3087
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Article: Obesity is associated with altered metabolic and reproductive activity in the mare: effects of metformin on insulin sensitivity and reproductive cyclicity.

Vick, M M / Sessions, D R / Murphy, B A / Kennedy, E L / Reedy, S E / Fitzgerald, B P

Reproduction, fertility, and development

2006 Volume 18, Issue 6, Page(s) 609–617

Abstract: In mares, obesity is associated with continuous reproductive activity during the non-breeding season. To investigate the effect of obesity and associated alterations in metabolic parameters on the oestrous cycle, two related studies were conducted. In ... ...

Abstract	In mares, obesity is associated with continuous reproductive activity during the non-breeding season. To investigate the effect of obesity and associated alterations in metabolic parameters on the oestrous cycle, two related studies were conducted. In Experiment 1, obese (body condition score > 7) mares were fed ad libitum or were moderately feed restricted during the late summer and autumn months. Feed restriction did not alter the proportion of mares entering seasonal anoestrus. However, obese mares exhibited a significantly longer duration of the oestrous cycle, significant increases in circulating concentrations of leptin and insulin, and decreased insulin sensitivity and concentrations of thyroxine compared with feed-restricted mares throughout the experiment. Experiment 2 was designed to investigate the effects of administration of the insulin-sensitising drug metformin hydrochloride on insulin sensitivity and the characteristics of the oestrous cycle in obese mares. In a dose-response trial, metformin increased insulin sensitivity after 30 days following administration of 3 g day(-1), but not 6 or 9 g day(-1), compared with controls receiving vehicle only. However, there were no differences in insulin sensitivity or oestrous cycle characteristics between control and metformin-treated groups when the 3 g day(-1) dose was tested for a longer period of 2 months. These results demonstrate that obesity is associated with aberrations in the oestrous cycle and perturbations in several markers of metabolic status. The results also indicate that metformin is not an effective long-term monotherapy for increasing insulin sensitivity in horses at the doses tested. Additional studies are needed to examine possible effects of increasing insulin sensitivity on reproductive activity in obese mares.
MeSH term(s)	Animals ; Breeding ; Dose-Response Relationship, Drug ; Estrous Cycle ; Female ; Food Deprivation ; Horse Diseases/drug therapy ; Horse Diseases/physiopathology ; Horses ; Hypoglycemic Agents/administration & dosage ; Insulin/blood ; Insulin Resistance ; Leptin/blood ; Metformin/administration & dosage ; Obesity/complications ; Obesity/physiopathology ; Obesity/veterinary ; Reproduction ; Seasons ; Thyroxine/blood
Chemical Substances	Hypoglycemic Agents ; Insulin ; Leptin ; Metformin (9100L32L2N) ; Thyroxine (Q51BO43MG4)
Language	English
Publishing date	2006-08-02
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1019913-5
ISSN	1448-5990 ; 1031-3613
ISSN (online)	1448-5990
ISSN	1031-3613
DOI	10.1071/rd06016
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