title: NPY and MC4R signaling regulate thyroid hormone levels during fasting through both central and peripheral pathways.
abstract: Fasting-induced suppression of the hypothalamic-pituitary-thyroid (HPT) axis is an adaptive response to decrease energy expenditure during food deprivation. Previous studies demonstrate that leptin communicates nutritional status to the HPT axis through thyrotropin-releasing hormone (TRH) in the paraventricular nucleus (PVN) of the hypothalamus. Leptin targets TRH neurons either directly or indirectly via the arcuate nucleus through pro-opiomelanocortin (POMC) and agouti-related peptide/neuropeptide Y (AgRP/NPY) neurons. To evaluate the role of these pathways in vivo, we developed double knockout mice that lack both the melanocortin 4 receptor (MC4R) and NPY. We show that NPY is required for fasting-induced suppression of Trh expression in the PVN. However, both MC4R and NPY are required for activation of hepatic pathways that metabolize T(4) during the fasting response. Thus, these signaling pathways play a key role in the communication of fasting signals to reduce thyroid hormone levels both centrally and through a peripheral hepatic circuit.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Vella
authors.forename: Preeti
authors.initials: P
authors.lastname: Ramadoss
authors.forename: Francis S
authors.initials: FS
authors.lastname: Lam
authors.forename: Jamie C
authors.initials: JC
authors.lastname: Harris
authors.forename: Felix D
authors.initials: FD
authors.lastname: Ye
authors.forename: Paul D
authors.initials: PD
authors.lastname: Same
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: O'Neill
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Maratos-Flier
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Hollenberg
mesh_terms: D015502:Absorptiometry, Photon; D000704:Analysis of Variance; D000818:Animals; D001823:Body Composition; D005215:Fasting / Q000502:physiology*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D017403:In Situ Hybridization; D020738:Leptin / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013963:Thyroid Hormones / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism
chemical_list: D020738:Leptin; D009478:Neuropeptide Y; D044105:Receptor, Melanocortin, Type 4; D013963:Thyroid Hormones; D013973:Thyrotropin-Releasing Hormone
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