Sucrose drinking mimics effects of nucleus accumbens µ-opioid receptor stimulation on fat intake and brain c-Fos-expression.

Objectives: We have previously shown that the combined consumption of fat and a sucrose solution induces overeating, and there is evidence indicating that sucrose drinking directly stimulates fat intake. One neurochemical pathway by which sucrose may enhance fat intake is through the release of endogenous opioids in the nucleus accumbens (NAC).Methods: To test this hypothesis, we provided rats with a free-choice high-fat diet for two weeks. During the second week, rats had access to an additional bottle of water or a 30% sucrose solution for five minutes per day. After these two weeks, we infused vehicle or the µ-opioid receptor agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) into the NAC 30 min after their daily access to the additional bottle of water or the sucrose solution.Results: Sucrose drinking had two effects, (1) it stimulated fat intake in the absence of DAMGO infusion, (2) it diminished sensitivity to DAMGO, as it prevented the rapid increase in fat intake typically seen upon DAMGO infusion in the nucleus accumbens. In a second experiment, we confirmed that these results are not due to the ingested calories of the sucrose solution. Lastly, we investigated which brain areas are involved in the observed effects on fat intake by assessing c-Fos-expression in brain areas previously linked to DAMGO's effects on food intake. Both intra-NAC DAMGO infusion and sucrose consumption in the absence of DAMGO infusion had no effect on c-Fos-expression in orexin neurons and the central amygdala but increased c-Fos-expression in the NAC as well as the basolateral amygdala.Discussion: In conclusion, we confirm that sucrose drinking stimulates fat intake, likely through the release of endogenous opioids.

A free-choice high-fat diet modulates the effects of a sucrose bolus on the expression of genes involved in glucose handling in the hypothalamus and nucleus accumbens.

The consumption of saturated fat and sucrose can have synergistic effects on the brain that do not occur when either nutrient is consumed by itself. In this study we hypothesize that saturated fat intake modulates glucose handling in the hypothalamus and nucleus accumbens, both brain areas highly involved in the control of food intake. To study this, male Wistar rats were given a free-choice high fat diet (fcHFD) or a control diet for two weeks. During the last seven days rats were given a daily bolus of either a 30% sucrose solution or water. Rats were sacrificed on day eight, 30 minutes after the onset of drinking. mRNA and protein levels of genes involved in glucose handling were assessed in the hypothalamus and nucleus accumbens. We found increased Glut3 and Glut4 mRNA in the hypothalamus of fcHFD-fed rats without an additional effect of the sucrose bolus. In the nucleus accumbens, the sucrose bolus increased Glut3 mRNA and decreased Glut4 mRNA independent of prior diet exposure. The ATP-sensitive potassium channel subunit Kir6.1 in the nucleus accumbens tended to be affected by the synergistic effects of a fcHFD and a sucrose bolus. These data suggest that acute glucose handling in the hypothalamus and nucleus accumbens may be affected by prior high fat exposure.