Glucocorticoids And Insulin Both Modulate Caloric Intake Through Actions On The Brain

J Physiol 583.2 (2007) pp 431–436

431

SYMPOSIUM REPORT

Glucocorticoids and insulin both modulate caloric intake through actions on the brain
Mary F. Dallman, James P. Warne, Michelle T. Foster and Norman C. Pecoraro
Department of Physiology, University of California San Francisco, CA 94143, USA

Glucocorticoids act primarily in a feed-forward fashion on brain to activate CNS pathwaysthat implement wanting appropriate to physiological needs. Thus, depending on the available conditions, elevated glucocorticoids may augment the behavioural want to run, fight or feed. Although glucocorticoids stimulate intake of chow, fat and sucrose, insulin appears to sculpt calorie-associated desires toward foods high in fat, acting through hepatic branch afferents of the vagus nerve. Bothconditions of reduced food allowance and chronic stress excite glucocorticoid-augmented central neural networks that may lead toward ultimate abdominal obesity.
(Received 10 May 2007; accepted after revision 6 June 2007; first published online 6 June 2007) Corresponding author M. Dallman: Department of Physiology, Box 0444, University of California San Francisco, 513 Parnassus Avenue, San Francisco,CA 94143-0444, USA. Email: mary.dallman@ucsf.edu

Adrenal glucocorticoids (GC) are well known to mobilize substrate from peripheral energy depots such as muscle and fat for use in hepatic gluconeogenesis, insuring a plentiful supply of glucose for use under conditions of challenge when flight or fight may be necessary. However, GC also have marked and complementary effects on the brain, that serveto augment behaviours, autonomic and neuroendocrine outflows, and learning and memory that are particularly associated with body energy balance and maintenance of life during challenging periods. During the past decade our lab has been exploring the roles of energy stores, GC and insulin on feeding behaviours and central stress responses (Pecoraro et al. 2006). Below we review studies that showwhen adrenalectomized (ADX) rats are provided with highdensity sucrose solutions, the rats normalize caloric stores and central corticotropin-releasing factor (CRF) expression to those levels that are observed in shamoperated animals. Drinking the pleasurable, high density calories restores neuroendocrine, autonomic outflows and energy stores to normal in rats without GC. This finding suggested a newworking model for feedback in the hypothalamo-pituitary adrenal (HPA) axis that we have since tested. Ingestion of sweet (sucrose and saccharin)

and fat (lard) substances, and searching for rewarding food, and memory for it, is proportional to the circulating GC environment, again invoking the powerful effects of GC on shaping behaviours associated with feeding. GC also stimulate insulinsecretion, and we have found that it is the interaction between GC and insulin that modulates the choice of fat (lard) intake. The action of insulin is on the liver, probably through insulin receptors, and mediated through hepatic branch vagal afferents to the brain to provoke lard intake. In the absence of insulin, lard eating does not persist beyond one day in diabetic rats. Thus, through a variety ofdifferent mechanisms, the GC insure caloric intake particularly intake of high-density, pleasurable calories. In the presence of chronic stressors, this type of feeding may become habitual. If increased intake of comfort foods does become a habit, abdominal obesity may result, leading to many of the current ills of our society (Dallman et al. 2007).

Adrenalectomy and sucrose: a new model offeedback regulation in the HPA axis (Fig. 1)

This report was presented at The Journal of Physiology Symposium on Obesity and the central nervous system, Washington, DC, USA, 1 September 2007. It was commissioned by the Editorial Board and reflects the views of the author.
C

When ADX rats are given saline to drink (thus preventing sodium depletion due to loss of aldosterone) and chow to eat...