Corticosterone-dependent metabolic and neuroendocrine abnormalities in obese Zucker rats in relation to feeding.
The obese Zucker (fa/fa) rat is characterized by hyperphagia, hyperinsulinemia, an increase in fat deposition, and a hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis in fa/fa rats is hypersensitive to stressful experimental conditions. Food deprivation even leads to a stress reaction in obese fa/fa rats. The present study was conducted to investigate the role of corticosterone in obese rats on the basal, fasting, and postprandial metabolic rate as well as on the central expression of the thyrotropin-releasing hormone (TRH) in these conditions. In addition, the study was aimed at clarifying whether the high levels of corticosterone in obese rats are responsible for the induction of the stress reaction to food deprivation in these animals. The present results demonstrate that whole body fat oxidation and postprandial metabolic responses in obese Zucker rats were improved by adrenalectomy (ADX). At the level of the central nervous system, ADX reversed a decrease in TRH mRNA expression in the paraventricular hypothalamus (PVH) detected in fasting animals. Considering all feeding conditions, the obese rats demonstrated lower TRH mRNA levels compared with lean animals. ADX resulted in an enhanced postprandial activation of the parvocellular PVH. In contrast, the magnocellular part of the PVH was less responsive to refeeding in ADX animals. Finally, ADX failed to prevent the stress response of obese rats to food deprivation. The present results provide evidence that the removal of adrenals resolve some of the metabolic defects encountered in obese Zucker rats. They also demonstrate that not all the abnormalities of the obese Zucker rats are attributable to the hyperactivity of the HPA axis.
Duclos
Martine
M
Laboratoire Neurogénétique, Université Laval, Quebec, Canada.
Timofeeva
Elena
E
Michel
Chantal
C
Richard
Denis
D
D000818:Animals; D001786:Blood Glucose; D001823:Body Composition / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D003345:Corticosterone / Q000097:blood*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D004435:Eating / Q000502:physiology*; D005508:Food Deprivation / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007328:Insulin / Q000097:blood; D008297:Male; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology*; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011924:Rats, Zucker; D013312:Stress, Physiological / Q000503:physiopathology; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics
D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone