Pituitary Lesions, Obesity, and Mesenteric Lipomas in Insulin-Resistant Horses

The aim of the current study was to identify associations between pituitary lesions, body condition scores, and mesenteric lipomas in horses with insulin resistance. Necropsy examinations were performed following euthanasia in 30 adult horses designated as insulin resistant (n = 11) or insulin sensitive (n = 19). Insulin sensitivity was determined using the insulin-modified frequently sampled intravenous glucose tolerance test and resting insulin concentrations. At necropsy, mesenteric lipomas were measured. The pituitary and adrenal glands, pancreas, and liver were evaluated histologically; pituitary glands were scored based on published criteria. Insulin-resistant horses had significantly higher pituitary scores (p = 0.0035) and body condition scores (p = 0.0001), even when adjusting for age, and a greater frequency of mesenteric lipomas (p = 0.014) and greater lipoma area (p = 0.0332) than insulin-sensitive horses. Regardless of insulin status, horses with pituitary scores ≥3 (diffuse hyperplasia; n = 25) had higher body condition scores (p = 0.0313) and a greater frequency of mesenteric lipomas (p \u3c 0.0002) than those with lower pituitary scores. High body condition score was not correlated to an increased frequency of mesenteric lipomas. Detection of higher pituitary scores in insulin-resistant horses suggested an association between insulin resistance and pituitary morphology. Horses in the insulin-resistant group and those with high pituitary scores had higher body condition scores and a greater frequency of mesenteric lipomas. These horses might be at increased risk for lipoma-associated colic

Kisspeptin receptor agonist (FTM080) increased plasma concentrations of luteinizing hormone in anestrous ewes

Kisspeptin receptor (KISS1R) agonists with increased half-life and similar efficacy to kisspeptin in vitro may provide beneficial applications in breeding management of many species. However, many of these agonists have not been tested in vivo. These studies were designed to test and compare the effects of a KISS1R agonist (FTM080) and kisspeptin on luteinizing hormone (LH) in vivo. In experiment 1 (pilot study), sheep were treated with FTM080 (500 pmol/kg BW) or sterile water (VEH) intravenosuly. Blood was collected every 15 min before (1 h) and after (1 h) treatment. In experiment 2, sheep were treated with KP-10 (human Metastin 45-54; 500 pmol/kg BW), one of three dosages of FTM080 (500 (FTM080:500), 2500 (FTM080:2500), or 5000 (FTM080:5000) pmol/kg BW), or VEH intravenously. Blood was collected every 15 min before (1 h) and after (4 h) treatment. In experiment 1, FTM080:500 increased (P < 0.05) plasma LH concentrations when compared to VEH. The area under the curve (AUC) of LH following FTM080:500 treatment was also increased (P < 0.05). In experiment 2, plasma LH concentrations increased (P < 0.05) following treatment with KP-10 and FTM080:5000 when compared to VEH and FTM080:500. The AUC of LH following KP-10 was greater than (P < 0.05) all other treatments and the AUC of LH following FTM080:5000 was greater than (P < 0.05) all treatments except KP-10. These data provide evidence to suggest that FTM080 stimulates the gonadotropic axis of ruminants in vivo. Any increased half-life and comparable efficacy of FTM080 to KP-10 in vitro does not appear to translate to in vivo in sheep