Role of the bombesin-like peptide system in the network regulating energy metabolism

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Fatty acids have an important role to convey energy state of the whole body to the brain. We studied whether the bombesin-like peptide system is involved in this regulation, by using BRS-3 (bombesin-like peptide receptor 3) knock-out mice.Knock-out mice at 30-weeks-old were obese, and fatty acids (palmityl acid, oleic acid, etc) content in the blood was elevated despite of its decrease in the brain. In the knock-out mice, feeding-suppressing effect of oleic acid injected intracerebroventricularly was decreased. On the other hand, octanoic acid did not affect the feeding in both wild and knock-out mice. Then, we used cFos expression as the neural activation marker. Administration of oleic acid into the wild type mice induced cFos expression in the hypothalamus, but in the knock-out mice this effect was not observed. Using in situ hybridization, it is shown that the BRS-3-positive cells in the arcuate nucleus of the hypothalamus did not express at detectable level feeding-promoting peptide such as NPY and AgRP, and feeding-suppressing peptide such as CART and POMC. When the isolated cells from the arcuate nucleus of the wild or knock-out mice were assayed by the calcium imaging technique, they responded to the fatty acids. The response of the BRS-3-expressing cells should be isolated and analyzed in this experiment in the future.From these results, we concluded that the BRS-3 expressing cells in the arcuate nucleus were involved in the regulation of the feeding by the fatty acids. These results demonstrated one aspect of mechanism of fatty acids action on the feeding, and are important because they may be associated with the incidence of the metabolic syndrome.