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Butterfat is the most important nutritional ingredient in milk, its precursors mainly include ethanoic aid,β-hydroxybutyric acid (BHBA), nonesterified fatty acid (NEFZ) and Triglyceride etc.Neuroendocrine network can act on liver and adipose tissue to control lipid metabolism for satisfying synthesis of butterfat.Then, there is not report about whether butterfat precursors can feedback regulate neuroendocrine network to maintain milk synthesis dynamic balance.Studies indicated BHBA can also act as signal molecule by binding with its receptor GPR109A to develop certain physiologic function in vivo.We have verified that GPR109A expresses not only in dairy cow but also in rat hypothalamus, so our experiment used rat hypothalamic neurons for pattern cells.In order to study whether BHBA can regulate the secretion function of hypothalamus.Wistar neonate rat hypothalamic neurons were isolated and cultured.At the seventh day of culturing, cells were treated with different concentrations of BHBA (0, 0.05, 0.5, 1 and 2 mmol/L).After 24 h, cells and supernatant were collected, then extracted total RNA.The gene expression and secretion of growth hormone-releasing hormone (GHRH), corticotrophin-Releasing Hormone (CRH), somatostatin (SST) and prolactin release-Inhibiting factor (PIF) were detected with real-time PCR and ELISA methods.The results showed, with the increasing of BHBA concentration, the inhibitory action of GHRH,CRH and PIF gene expression and protein secretion gradually increased.While SST gene expression and protein secretion showed low concentration to promote and high concentration to inhibit.The result suggested that BHBA may act as signal molecule regulating secretion function ofhypothalamus.