Glucocorticoid receptor density correlates with health risk factors and insulin resistance in Caucasian and African American subjects.

Activation of the hypothalamic-pituitary-adrenal axis leads to secretion of cortisol, which binds to peripheral glucocorticoid receptor and mediates a complex series of metabolic and immune effects. Cortisol also binds to receptors in the hypothalamus and pituitary, and inhibits further secretion of adrenocorticotropic hormone thus preventing an excessive response. Excess glucocorticoid effect is seen in Cushings disease, adrenal adenomas/carcinomas and in glucocorticoid resistance. Within such pathology there are health consequences of excessive glucocorticoid action, including obesity, hypertension, and glucose intolerance or diabetes. We hypothesized that increased glucocorticoid receptor in peripheral tissue might mediate an excess glucocorticoid effect in the absence of increased cortisol secretion. The objective of the study was to investigate the relationship between glucocorticoid receptor density in leukocytes and health risk indices relevant to obesity and diabetes in a sample of Caucasian and African American subjects. Comparison of glucocorticoid receptor concentration with subject body mass index, percentage body fat, waist circumference, insulin resistance, plasma cortisol levels, gender, and lipid profiles were conducted. Increased glucocorticoid receptor density significantly correlated with body mass index, percentage body fat, waist circumference, and insulin resistance. No significant correlation was observed for glucocorticoid receptor density with lipid profiles. Furthermore, no significant differences were observed in glucocorticoid receptor density between Caucasian and African American subjects or male and female participants. Our results show that high risk health conditions, such as obesity and type-2 diabetes, may be associated with a form of hypothalamic-pituitary-adrenal axis dysfunction, characterized by localized leukocyte glucocorticoid receptor over-expression.

Changes in plasma volatile fatty acids in response to weaning and feed intake in young calves.

Effects of weaning age on plasma VFA were examined using 16 Holstein heifer calves. Animals entered the study at 6 +/- 3.5 d of age and were fed 1.8 kg milk twice daily to 28 (early weaning) or 56 d (late weaning) and a commercial pelleted calf starter from 0 (early) or 28 (late) d. Blood was sampled once weekly for 14 wk. Total blood concentrations of VFA, acetate, propionate, and butyrate were higher in calves weaned early. Difference between treatments was greatest during wk 5 to 8, after early calves had been weaned. Total VFA and acetate were both highly correlated with grain intake (r = .77), whereas propionate (r = .47) and butyrate (r = .56) were less highly correlated. Data indicate that blood VFA responded rapidly to dry feed intake, and adaptation to high grain diets was complete by 1 to 2 wk postweaning.