Abnormal Regulation of the Hypothalamo-Pituitary Adrenal Axis in the Genetically Obesefa/faRat*

Abstract

Adrenalectomy has been shown to reverse most facets of the syndrome of the genetically obese fa/fa rat. However, a detailed analysis of the hypothalamo-pituitary-adrenal (HPA) axis in these animals is lacking. In the present study, morning corticosteronemia was higher in obese rats of both sexes than in lean ones, whereas evening corticosteronemia was higher only in obese male rats. The HPA axis was further investigated using stressful stimuli. Immobilization, ether, and cold stresses resulted in greater corticosterone levels in obese than in lean animals. These abnormalities consisted in upward shifts of the corticosterone response in obese females and absolute increases in that of obese males, indicating that such alterations were more pronounced in obese male than obese female rats. Due to this, the putative origin of the increased corticosterone output of obese rats was studied in males. Greater levels of ACTH were reached in obese than in lean rats when submitted to a cold stress (6 C). Dexamethasone produced a complete suppression of corticosterone output in both lean and obese rats. During the recovery from such suppression, corticosterone levels rose to higher values in obese than in lean rats. This observation together with the greater cold-induced ACTH output in obese rats suggest that the increased activity of the HPA axis of these animals is of central origin. Whatever its precise etiology within the central nervous system, it is proposed that the increased HPA axis activity in obese rats and its resultant hypercorticism play a role in the establishment and maintenance of their syndrome.

Effects of the CRF1 receptor antagonist SSR125543 on energy balance and food deprivation-induced neuronal activation in obese Zucker rats

“…As expected, CRF 1 receptor blockade attenuated the activity of the HPA axis. Three weeks of treatment with SSR125543 reduced the basal plasma corticosterone levels in lean rats and prevented the fastinginduced corticosterone response in obese Zucker rats, which are hypercorticosteronemic (Guillaume-Gentil et al 1990, Richard et al 1996 and hypersensitive to stress (GuillaumeGentil et al 1990, Timofeeva & Richard 1997. Similarly, a previous study showed that SSR125543 reduced the basal adrenocorticotropic hormone (ACTH) concentrations and attenuated the CRF-and stress-induced increase in circulating ACTH in Sprague-Dawley rats .…”

Overweight and Metabolic and Hormonal Parameter Disruption Are Induced in Adult Male Mice by Manipulations During Lactation Period

“…Indeed, the administration of GC in the neonatal period produces in adults a decrease in the expression of GC receptors in several areas of the brain, and this could explain the disruption of feedback mechanisms (34). High levels of plasma corticosterone and/or ACTH are found in other models of obesity in rodents (35,36), and in humans, the HPA seems to contribute to the metabolic syndrome (37). Moreover, cortisol is elevated in patients with type 1 and diabetes, and in many of them, GC administration Values are mean Ϯ SEM of at least three cages, each containing three animals (cumulative daily food intake).…”

Interactions between the neuropeptide Y system and the hypothalamic-pituitary-adrenal axis

“…The altered activity of the hypothalamic NPY system in these rats results, not only from insensitivity to insulin (53) and mutations of the leptin receptor (4), but also from increased plasma corticosterone concentrations (56) and increased sensitivity to corticosterone (57). In turn, NPY increases, via a positive feedback, plasma corticosterone concentrations (32).…”