Influence of castration-induced testosterone and estradiol deficiency on obesity and glucose metabolism in male Göttingen minipigs.

Low testosterone and estradiol concentrations are predictive for the development of the metabolic syndrome in men and women, respectively. The aim of this study was to investigate the influence of sex hormone deficiency on food intake, body weight, body composition and glucose metabolism in male Göttingen minipigs. Five adult male Göttingen minipigs were studied before castration (pre-cast), 10-18 days (post-cast 1) and 10-11 weeks (post-cast 2) after castration. Parameters of interest were food intake, body weight, body fat percentage and sex hormone concentrations. Furthermore glucose tolerance, glucagon suppression, insulin resistance, beta cell function and disposition index were evaluated by oral and intravenous glucose tolerance tests. Castration led to almost complete disappearance of circulating testosterone and estradiol and secondarily to increased food intake, body weight and body fat percentage. Ten-eighteen days sex hormone deficiency (post-cast 1) did not significantly change any of the investigated metabolic parameters compared to pre-cast levels. Ten weeks after castration (post-cast 2) significant insulin resistance, glucose intolerance and hyperglucagonemia was found, and the beta cell function and the disposition index both were decreased. In conclusion, castration-induced sex hormone deficiency in male Göttingen minipigs results in hyperphagia, obesity and disturbed glucose metabolism, which are some of the features typical for the human metabolic syndrome.

Gender-associated differences in metabolic syndrome-related parameters in Göttingen minipigs.

Gender-associated differences in pathophysiology and treatment of disease are an evolving area in human medicine that should be addressed in animal models. The aim of this study was to characterize gender differences in metabolic parameters of Göttingen minipigs and to determine which gender has the metabolic profile that is most appropriate as a model for human metabolic syndrome. Blood samples were collected from fasted, lean male and female Göttingen minipigs at 8 wk and 8 mo of age. Samples were analyzed for glucose, fructosamine, insulin, C-peptide, glucagon, triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-c), free fatty acids, leptin, testosterone, and 17beta-estradiol. Insulin sensitivity and beta cell function were estimated by homeostasis model assessment and degree of obesity by measuring the abdominal circumference. Male minipigs had higher concentrations of both testosterone and estradiol. Female minipigs had a larger abdominal circumference and higher concentrations of C-peptide, insulin, triglyceride, total cholesterol, HDL-c and leptin but a lower concentration of free fatty acids and lower HDL-c:total cholesterol ratio. Compared with male minipigs, female minipigs were more insulin-resistant and had a higher beta-cell function. No gender-associated differences were found in any of the other investigated parameters. In conclusion, female minipigs were more obese and insulin-resistant and had a more atherogenic plasma profile than did their male counterparts and therefore may be better models for metabolic syndrome. Their high concentrations of both testosterone and estradiol may protect male minipigs from obesity and metabolic disturbances.