Glucocorticoids and insulin both modulate caloric intake through actions on the brain

Abstract

Glucocorticoids act primarily in a feed-forward fashion on brain to activate CNS pathways that 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. Both conditions of reduced food allowance and chronic stress excite glucocorticoid-augmented central neural networks that may lead toward ultimate abdominal obesity.

Figure 1. New working model for regulation of activity in the HPA axis

The schema on the left shows the standard GC-mediated feedback of HPA function on the brain as well as the fact that the GC act on peripheral energy stores. The schema on the right shows our current working model. Note that the effect of GC on brain is now excitatory, and that there is a signal from energy stores that now is inhibitory on the brain and HPA axis (GC, glucocorticoids; CNS, central nervous system; CRF, corticotropin-releasing factor; MA, monoamines; DA, dopamine).

Figure 2. Sucrose ingestion is inversely related to CRF mRNA in the paraventricular nuclei (PVN)

In bilaterally adrenalectomized rats, the total sucrose intake during the 9 days it was available is tightly related to the expression of hypothalamic CRF. CRF mRNA was restored to values similar to those in sham-operated rats (5 points on the right) reducing the normally elevated CRF seen in adrenalectomized rats (4 points on the left) to values similar to rats with intact adrenals (data from Laugero et al. 2001).

Figure 3. Corticosterone has opposite effects on body weight gain and mesenteric fat weight

In adrenalectomized, corticosterone-treated rats allowed sucrose to drink ad libitum, body weight decreases (left panel) as mesenteric fat weight increases (right panel) showing a central shift of calorie storage (data from Bell et al. 2000).

Figure 4. As corticosterone increases, circulating insulin increases

In adrenalectomized, corticosterone-treated rats allowed lard to eat ad libitum, plasma insulin increased with steady-state corticosterone concentrations. This also occurs in similarly treated rats allowed only chow, but the extent of the effect is greater when the rats are also given the choice of lard to eat (data from la Fleur et al. 2004).

Figure 5. Outline of paradigm to determine how the hepatic branch vagus modulates lard intake

In published and ongoing experiments we are testing the role of the hepatic branch of the vagus (which includes afferents and efferents to both the liver and gastroduodenum), the gastroduodenal branch of the hepatic vagus, and the role of afferent nerves from both sites. The anatomy is indicated for the part of the vagus nerve of interest. Scissors and dotted lines denote severing the nerve; the x indicates the site of painting the nerve with capsaicin in an attempt to destroy afferent fibres without impairing the efferents (experiments of Warne et al. 2006).