title: Absence of TRH receptor 1 in male mice affects gastric ghrelin production.
abstract: TRH not only functions as a thyrotropin releasing hormone but also acts as a neuropeptide in central circuits regulating food intake and energy expenditure. As one suggested mode of action, TRH expressed in the caudal brainstem influences vagal activity by activating TRH receptor 1 (TRH-R1). In order to evaluate the impact of a diminished medullary TRH signaling on ghrelin metabolism, we analyzed metabolic changes of TRH-R1 knockout (R1ko) mice in response to 24 hours of food deprivation. Because R1ko mice are hypothyroid, we also studied eu- and hypothyroid wild-type (wt) animals and R1ko mice rendered euthyroid by thyroid hormone treatment. Independent of their thyroidal state, R1ko mice displayed a higher body weight loss than wt animals and a delayed reduction in locomotor activity upon fasting. Ghrelin transcript levels in the stomach as well as total ghrelin levels in the circulation were equally high in fasted wt and R1ko mice. In contrast, only wt mice responded to fasting with a rise in ghrelin-O-acyltransferase mRNA expression and consequently an increase in serum levels of acylated ghrelin. Together, our data suggest that an up-regulation of medullary TRH expression and subsequently enhanced activation of TRH-R1 in the vagal system represents a critical step in the stimulation of ghrelin-O-acyltransferase expression upon starvation that in turn is important for adjusting the circulating levels of acylated ghrelin to the fasting condition.
authors.affiliation: Leibniz Institute for Age Research/Fritz Lipmann Institute (S.M., C.L., H.H.), D-07745 Jena, Germany; Brandenburg University of Technology Cottbus-Senftenberg (C.L.), D-01968 Senftenberg, Germany; Department of Internal Medicine (T.J.V.), Erasmus Medical Center, Rotterdam, The Netherlands; and Leibniz Research Institute for Environmental Medicine (H.H.), Düsseldorf, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Mayerl
authors.forename: Claudia
authors.initials: C
authors.lastname: Liebsch
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Heike
authors.initials: H
authors.lastname: Heuer
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D004435:Eating; D005215:Fasting / Q000502:physiology*; D005508:Food Deprivation; D005753:Gastric Mucosa / Q000378:metabolism*; D054439:Ghrelin / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D008565:Membrane Proteins; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000378:metabolism*; D013963:Thyroid Hormones / Q000097:blood*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism
chemical_list: D054439:Ghrelin; D008565:Membrane Proteins; D018025:Receptors, Thyrotropin-Releasing Hormone; D013963:Thyroid Hormones; D013973:Thyrotropin-Releasing Hormone; D000217:Acyltransferases; C526983:Mboat4 protein, mouse