| LDR | | 00000nam u2200205 4500 |
| 001 | | 000000435585 |
| 005 | | 20200228101401 |
| 008 | | 200131s2019 ||||||||||||||||| ||eng d |
| 020 | |
▼a 9781392609460 |
| 035 | |
▼a (MiAaPQ)AAI13859085 |
| 040 | |
▼a MiAaPQ
▼c MiAaPQ
▼d 247004 |
| 082 | 0 |
▼a 612 |
| 100 | 1 |
▼a Anderson, Erica J. P. |
| 245 | 10 |
▼a Roles of Melanocortin-4 Receptor Signaling Partner Kir7.1 in Energy Homeostasis. |
| 260 | |
▼a [S.l.]:
▼b Vanderbilt University.,
▼c 2019. |
| 260 | 1 |
▼a Ann Arbor:
▼b ProQuest Dissertations & Theses,
▼c 2019. |
| 300 | |
▼a 150 p. |
| 500 | |
▼a Source: Dissertations Abstracts International, Volume: 81-05, Section: B. |
| 500 | |
▼a Advisor: Winder, Danny G. |
| 502 | 1 |
▼a Thesis (Ph.D.)--Vanderbilt University, 2019. |
| 506 | |
▼a This item must not be sold to any third party vendors. |
| 520 | |
▼a Energy stores in fat tissue are determined in part by the activity of the hypothalamic neurons expressing the melanocortin-4 receptor (MC4R). Even partial reduction in MC4R expression levels in mice, rats, or humans produces hyperphagia and morbid obesity. Thus it is of great interest to understand the molecular basis of neuromodulation by the MC4R. The MC4R is a G-protein coupled receptor (GPCR) that signals efficiently through Gs, and this signaling pathway is essential for normal MC4R function in vivo. However, previous data from hypothalamic slice preparations indicated that activation of the MC4R depolarized neurons through G protein-independent regulation of the ion channel Kir7.1. Herein a panel of mouse models are used to study the physiologic and pharmacologic effects of loss of Gs and Kir7.1. Deletion of Kcnj13, the gene encoding Kir7.1, specifically from MC4R neurons produced resistance to melanocortin peptide-induced depolarization of MC4R PVN neurons in brain slices, resistance to the sustained anorexic effects of exogenously administered melanocortin peptides, late onset obesity, increased linear growth, and glucose intolerance. Some MC4R-mediated phenotypes appeared intact, including AgRP-induced stimulation of food intake, and MC4R-mediated induction of PYY release from intestinal L cells. Thus, a subset of the consequences of MC4R signaling in vivo appear dependent on expression of the Kir7.1 channel in MC4R cells. |
| 590 | |
▼a School code: 0242. |
| 650 | 4 |
▼a Molecular biology. |
| 650 | 4 |
▼a Endocrinology. |
| 650 | 4 |
▼a Physiology. |
| 690 | |
▼a 0307 |
| 690 | |
▼a 0409 |
| 690 | |
▼a 0719 |
| 710 | 20 |
▼a Vanderbilt University.
▼b Molecular Physiology and Biophysics. |
| 773 | 0 |
▼t Dissertations Abstracts International
▼g 81-05B. |
| 773 | |
▼t Dissertation Abstract International |
| 790 | |
▼a 0242 |
| 791 | |
▼a Ph.D. |
| 792 | |
▼a 2019 |
| 793 | |
▼a English |
| 856 | 40 |
▼u http://www.riss.kr/pdu/ddodLink.do?id=T15490879
▼n KERIS
▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
| 980 | |
▼a 202002
▼f 2020 |
| 990 | |
▼a ***1008102 |
| 991 | |
▼a E-BOOK |