Hypercorticosteronemia induces hyperphagia and obesity in human growth hormone transgenic rats

Hyperphagia and subsequent obesity are important public health issues due to the associated risks of developing serious diseases. Certain stressors play a major role in the development of hyperphagia. In previous studies, we established a line of human growth hormone transgenic (TG) rats that exhibit hyperphagia and obesity from a young age. We recently demonstrated that voluntary running on a running wheel alleviates hyperphagia in TG rats. Wheel running provides environmental enrichment for rodents and plays a role in relieving stress. These results suggested that stress is the major factor inducing hyperphagia in TG rats. Thus, in the present study, we evaluated activation of the hypothalamus-pituitary-adrenal axis. TG rats showed bilateral enlargement of adrenal glands and hypercorticosteronemia, although their hypothalamic CRH level was comparable to that of wild-type (WT) rats. The ACTH-immunoreactive area was larger and the serum ACTH level in the dark phase was higher in TG rats than in WT rats. Adrenalectomy reduced the food intake of TG rats to a level comparable to that in WT rats, and supplying glucocorticoids recurred hyperphagia in TG rats. These treatments did not affect the food intake of WT rats. Rearing TG rats under group housing prevented hyperphagia and hypercorticosteronemia. These results suggest that glucocorticoids are appetite stimulants, and that TG rats exhibit increased sensitivity to the appetite-stimulating effect of glucocorticoids.