Abstract
The hypothalamic AMP kinase regulates feeding behavior in response to hormonal and nutrient signals. Decrease of AMPK activity in the paraventricular (PVH) and arcuate (ARH) hypothalamus plays an important role in anorexic effect of leptin. In the present study, we examined the long-term expression of constitutively-active AMP kinase (CA-AMPK) in the PVH in C57/BL6 mice in food intake and body weight, using lenti-viral vector with neuron specific-synapsin 1 promotor. CA-AMPK in the PVH gained body weight and increased food intake in mice: the increase in body weight was more than 10 g in CA-AMPK expressed mice 3 months after the infection, while the increase in the control mice was less than 4 g. Interestingly, CA-AMPK in the PVH increased the preference for high carbohydrate but not high fat diet, while the control mice preferred high fat diet rather than high carbohydrate diet. As shown in peripheral tissues by several reports, we found that CA-AMPK increased the expression of fatty acid oxidation-related genes such as PPAR alpha, FATP1, CPT1c, etc. in the PVH. Furthermore, direct administration of etomoxir, an inhibitor of CPT-1 and fatty acid oxidation in mitochondria, into the PVH in the CA-AMPK expressed mice, reversed the high preference for carbohydrate diet to the preference for high fat diet. Thus, these findings suggest that AMP kinase in the PVH regulates not only calorie intake but also the preference for carbohydrate and fat diets, by changing fatty acid metabolism in the hypothalamic nucleus. [J Physiol Sci. 2007;57 Suppl:S72]
