Abstract
BackgroundBrainstem thyrotropin‐releasing hormone (TRH) resides in nerve fibers innervating sympathetic and vagal motor neurons and regulates food intake through vagal stimulation of ghrelin release (Endocrinology, 2006). TRH induced sympathetic activation is potentiated and vagal activation is impaired in GK rats, resulting in profound visceral dysfunctions (Endocrinology, 2005, Neuroscience, 2010, Hypertension Res 2011), including reduced food intake (Endo meeting 2010).MethodHypothalamic and brainstem gene expression relevant to food intake was measured by qPCR in Wistar and GK rats normally fed, fasted for 48 h and fasted for 48 h + refed 2 h.ResultsFasting increases TRH/TRH receptor mRNA in brainstem and ghrelin in serum in Wistar rats but not in GK rats. Fasting also increased hypothalamic gene expression of NPY, AgRP, ghrelin receptor, and leptin receptor, and decreased that of POMC in Wistar rats. These changes were not found in GK rats. Differences in gene expression of brainstem NPY, POMC, leptin receptor, MC4R, and 5‐HT receptor3a, and hypothalamic TRH, Y2 receptor and MC4R were found between fasted or refed Wistar and GK rats.Conclusionsympathovagal imbalance resulting from brainstem TRH dysfunction associates with disabled hypothalamic and brainstem responses to energy demand in T2D GK rats. Supported by VA Merit Ward (Yang).
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