Inhibitory effects of lipopolysaccharide on hypothalamic nuclei implicated in the control of food intake.

The arcuate nucleus (Arc) and the lateral hypothalamic area (LHA), two key hypothalamic nuclei regulating feeding behavior, express c-Fos, a marker of neuronal activation in fasted animals. This is reversed by refeeding. In the present study we tested whether an anorectic dose of lipopolysaccharide (LPS), the cell wall component of Gram-negative bacteria, also inhibits fasting-induced c-Fos expression in these hypothalamic nuclei. This would suggest that they are involved in anorexia during bacterial infections as well. We also studied whether LPS modulates the activity of orexin-A positive (OX+) LHA neurons. Food deprived BALB/c mice were injected with LPS or saline and were sacrificed 4 or 6h later. Four hours after injection, LPS reduced the number of c-Fos positive cells in the Arc and in the LHA, but had no effect on c-Fos in OX+ neurons. Six hours after injection, LPS reduced c-Fos expression in the LHA, both in the OX- and OX+ neurons, but not in the Arc. These results show that LPS modulates neuronal activity in the Arc and LHA similar to feeding-related stimuli, suggesting that the observed effects might contribute to the anorectic effect of LPS. Thus, physiological satiety signals released during refeeding and anorexia during bacterial infection seem to engage similar neuronal substrates.