Recipient Organization
TUFTS UNIVERSITY
200 WESTBORO ROAD
N. GRAFTON,MA 01536
Performing Department
Clinical Sciences
Non Technical Summary
Horses do not suffer from coronary artery disease, but a metabolic syndrome has been described in this species that is similar to Metabolic Syndrome (MetS) in humans. Equine metabolic syndrome (EMS) is a clinical syndrome of obesity or regional adiposity, hyperinsulinemia, insulin resistance (IR), and an increased predisposition to laminitis. Resveratrol, a plant phenol lowering blood cholesterol concentration in humans, has also been shown to improve insulin sensitivity in rodents and might therefore be effective for managing IR in horses. This study will evaluate the clinical efficacy of resveratrol in insulin-resistant horses. We hypothesize that resveratrol lowers plasma insulin concentrations, improves insulin sensitivity, and alters blood lipid concentrations in insulin-resistant horses.
Animal Health Component
20%
Research Effort Categories
Basic
80%
Applied
20%
Developmental
(N/A)
Goals / Objectives
We hypothesize that resveratrol lowers insulin concentrations, increases insulin sensitivity, alters blood lipid concentrations in horses with naturally-occurring hyperinsulinemia and insulin resistance (IR). These horses suffer from equine metabolic syndrome (EMS), which is a clinical syndrome of obesity or regional adiposity, hyperinsulinemia, IR, and an increased predisposition to laminitis. Our specific aims are: 1. To determine whether resveratrol lowers plasma insulin concentrations at rest and during dynamic tests. 2. To investigate the effects of resveratrol on insulin sensitivity in insulin-resistant horses. 3. To examine the effects of resveratrol on blood concentrations of adrenocorticotropin hormone (ACTH), leptin, triglyceride, non-esterified fatty acids, and cholesterol. Resveratrol is present in the skin of red grapes and therefore red wine and grape juice, and is also abundant within the dried roots of a plant called Japanese knotweed (Polygonum capsidatum). This phytochemical possesses cardiovascular protective properties that include reduced low-density lipoprotein (LDL) peroxidation, increased high-density lipoprotein (HDL) concentrations, and vasorelaxation. The beneficial effects of resveratrol on cardiovascular health explain the French Paradox, first described in 1992, which refers to the lower incidence of coronary heart disease in people that drink red wine while consuming a high-fat diet. Horses do not suffer from coronary artery disease, but a metabolic syndrome has been described in this species that is similar to Metabolic Syndrome (MetS) in humans. Metabolic Syndrome in humans represents a collection of risk factors that predict the occurrence of coronary artery disease and type 2 diabetes mellitus. Criteria for diagnosing MetS in humans include 1) increased waist circumference, 2) elevated plasma triglyceride concentrations, 3) low HDL-cholesterol, 4) elevated systolic blood pressure, and 5) high fasting glucose concentration. Equine Metabolic Syndrome also includes increased adiposity, with higher neck circumference values recorded, along with hyperinsulinemia and IR. Obesity and IR play important roles in both syndromes and are targets for management strategies. Results of different studies suggest that resveratrol lowers resting insulin concentrations and improves insulin sensitivity in animals with obesity and IR. Resveratrol appears to be most effective when used as protective agent in animals placed on high-calorie or high-cholesterol diets. In conclusion, results of studies performed in other mammalian species indicate that resveratrol can be used to treat or prevent hyperinsulinemia and IR in horses. Horses with EMS suffer from both conditions and have a higher incidence of hepatic lipidosis (unpublished data). Once we have determined the pharmacokinetics of resveratrol in horses, this nutraceutical should be evaluated as a treatment for hyperinsulinemia and IR in affected animals.
Project Methods
Study animals - Twenty adult horses with naturally-occurring fasting hyperinsulinemia will be enrolled in the study. Inclusion criteria will include fasting hyperinsulinemia and agreement from the owner for supplement administration and blood collection. Experimental design - A prospective clinical trial will be performed with client-owned horses, with investigators blinded to treatment and placebo group allocations. The identity of the capsules will be masked by numbering containers 1-20 randomly with treatment/placebo allocations within groups of 10. Horses will be randomly allocated to treatment and placebo groups, with treated horses receiving 2 capsules of trans resveratrol) twice daily, fed by hand. Note that the recommended preventive dose is 1 capsule twice daily. Animals in the placebo group will receive capsules containing the same natural compounds but not resveratrol. Assessment of endocrine/metabolic status 1. Insulin sensitivity and pancreatic insulin secretion will be assessed by performing an oral sugar test (OST) at 0 and 4 wk under short-term fasting conditions. 2. Resting leptin, adrenocorticotropin hormone (ACTH), triglyceride (TG), cholesterol, and non-esterified fatty acid (NEFA) concentrations will also be measured at 0 and 4 wk in blood collected at the start of the OST (time = 0). Morphometric measurements - Body weight will be measured with a weight tape and body condition score will be assessed using the 1 (poor) to 9 (extremely fat) scoring system. Neck circumference will be measured with a measuring tape by calculating the distance from the poll to the withers (x) and measuring the circumference of the neck at 0.25x, 0.5x, and 0.75x. Statistical analyses - Effects of treatment and period on resting and OST measurements will be assessed by analysis of variance analysis (ANOVA) for repeated measures.