Virilizing doses of testosterone decrease circulating insulin levels and differentially regulate insulin signaling in liver and adipose tissue of females.

Transgender men undergoing hormone therapy are at risk for insulin resistance. However, how virilizing testosterone therapy affects serum insulin and peripheral insulin sensitivity in transgender men is unknown. This study assessed the effect of acute, virilizing testosterone on serum insulin concentrations and insulin signaling in liver, skeletal muscle, and white adipose tissue (WAT) of female pigs as a translational model for transgender men. Females received three doses of intramuscular testosterone cypionate (TEST females; 50 mg/day/pig) or corn oil (control) spaced 6 days apart starting on the day of estrus (D0). Fasting blood was collected on D0, D3, D5, D11, and D13, and females were euthanized on D13. On D13, TEST females had virilizing concentrations of serum testosterone with normal concentrations of serum estradiol. Virilizing serum testosterone concentrations (D13) were associated with decreased serum insulin and C-peptide concentrations. Blood glucose and serum glycerol concentrations were not altered by testosterone. Virilizing concentrations of testosterone downregulated AR and ESR1 in subcutaneous (sc) WAT and upregulated transcript levels of insulin-signaling pathway components in WAT and liver. At the protein level, virilizing testosterone concentrations were associated with increased PI3K 110α in liver and increased insulin receptor (INSR) and phospho(Ser256)-FOXO1 in visceral (v) WAT but decreased phospho(Ser473)-AKT in vWAT and scWAT. These results suggest that acute exposure to virilizing concentrations of testosterone suppresses circulating insulin levels and results in increased abundance of proteins in the insulin-signaling pathway in liver and altered phosphorylation of key proteins in control of insulin sensitivity in WAT.NEW & NOTEWORTHY Acute virilizing doses of testosterone administered to females suppress circulating insulin levels, upregulate components of the insulin-signaling pathway in liver, and suppress insulin signaling in white adipose tissue. These results suggest that insulin resistance in transgender men may be due to suppression of the insulin-signaling pathway and decreased insulin sensitivity in white adipose tissue.

Dietary substitution of soybean oil with coconut oil in the absence of dietary antibiotics supports growth performance and immune function in nursery and grower pigs.

BACKGROUND: We hypothesized that supplementation of nursery and grower pig diets with coconut oil in the absence of antibiotics would yield maintenance of glucose homeostasis, growth performance, and immune function similar to what is achieved with nursery and grower pig diets containing antibiotics. Pigs received the same base treatment diets from d24 (weaning) to d71 of age and had blood and fecal samples collected on d24, d31, d45 and d71 for measurement of whole blood glucose, serum insulin, cortisol and cytokines, and fecal microbiome. Pigs had weekly weights and daily feed consumption measured throughout the study. Animals were euthanized at d71 and subcutaneous fat and ileal contents were collected for assessment for fatty acids and microbiome, respectively. Diet treatments consisted of 2% soybean oil plus antibiotics (ABX; n = 22), 2% soybean oil without antibiotics (NABX; n = 22), and 2% coconut oil without antibiotics (COC; n = 22). Statistical analysis examined the effect of diet within each timepoint using a repeated measures ANOVA. RESULTS: Pigs fed COC diet had decreased serum insulin levels, maintained feed intake, feed conversion and weight gain, and, based on serum cytokines and fecal microbiome, were immunologically similar to ABX-fed pigs. However, NABX-fed pigs performed similarly to the ABX-fed pigs in all parameters except for serum cytokines. Additionally, there was no difference in the incidence of diarrhea between any of the diet treatments. CONCLUSIONS: This study demonstrates that dietary antibiotics are not necessary to maintain growth performance in nursery and grower pigs. However, dietary antibiotics appear to modulate circulating cytokine levels. Dietary coconut oil is neither harmful nor helpful to growth performance or immune function in nursery and grower pigs but does modulate serum insulin levels. Therefore, while coconut oil fed at 2% by weight is a suitable substitute for dietary antibiotics, this study suggests that no substitute for dietary antibiotics is needed at all.

Exposure of managed red river hogs (Potamochoerus porcus) to urine from males stimulates estrous cycling and modulates fecal sex steroid metabolites in males and females.

For unknown reasons, reproductive success varies among zoos in managed red river hogs. In response to urine exposure from novel conspecifics, we hypothesized that males with low libido would exhibit increased concentrations of testosterone metabolites and that acyclic and/or non-breeding females would be induced to cycle or cycle more regularly. Estrous cycle length and progesterone metabolites in same-sex housed females were compared prior to and following exposure to novel red river hog male urine. Male testosterone metabolites and female progesterone metabolites as well as estrous cycle length were compared among: 1) proven-breeder females and males; 2) non-breeding females newly paired with novel males; 3) non-breeding females and males exposed to urine from novel females and males. Fecal samples were collected 3-5 times per week for eight to 12 months, lyophilized, extracted, and assayed for progesterone and testosterone metabolites with validated enzyme immunoassays. Introduction of female urine resulted in an increased number of estrous cycles per female per month, and decreased luteal and increased follicular progesterone metabolites in females. Introduction of male urine resulted in an increase in testosterone metabolites in males. Average progesterone metabolites for pregnant proven-breeder females were more than double that for pregnant females newly paired to novel males. An interaction between season and treatment group, as well as the acyclicity of females from July through November irrespective of treatment group, suggest that season may confound and warrant judicious interpretation of the results. Additionally, females housed with pregnant females were either acyclic or did not carry their pregnancies to term, indicating that reproductive suppression may occur in females. In conclusion, urine may be a cost-effective and efficient means to manipulate estrous cycling in managed red river hogs. Furthermore, careful consideration of the number of females in a managed herd is recommended to avoid reproductive suppression.