دورية أكاديمية
A gain-of-function mutation in adenylate cyclase 3 protects mice from diet-induced obesity.
العنوان: | A gain-of-function mutation in adenylate cyclase 3 protects mice from diet-induced obesity. |
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المؤلفون: | Jeffrey L Pitman, Matthew C Wheeler, David J Lloyd, John R Walker, Richard J Glynne, Nicholas Gekakis |
المصدر: | PLoS ONE, Vol 9, Iss 10, p e110226 (2014) |
بيانات النشر: | Public Library of Science (PLoS), 2014. |
سنة النشر: | 2014 |
المجموعة: | LCC:Medicine LCC:Science |
مصطلحات موضوعية: | Medicine, Science |
الوصف: | In a screen for genes that affect the metabolic response to high-fat diet (HFD), we selected one line of N-ethyl-N-nitrosourea (ENU)-mutagenized mice, Jll, with dominantly inherited resistance to diet-induced obesity (DIO). Mutant animals had dramatically reduced body weight and fat mass, and low basal insulin and glucose levels relative to unaffected controls. Both white adipose tissue (WAT) and brown adipose tissue (BAT) depots were smaller in mutant animals. Mutant animals fed a HFD gained only slightly more weight than animals fed regular chow, and were protected from hepatic lipid accumulation. The phenotype was genetically linked to a 5.7-Mb interval on chromosome 12, and sequencing of the entire interval identified a single coding mutation, predicted to cause a methionine-to-isoleucine substitution at position 279 of the Adcy3 protein (Adcy3M279I, henceforth referred to as Adcy3Jll). The mutant protein is hyperactive, possibly constitutively so, producing elevated levels of cyclic AMP in a cell-based assay. These mice demonstrate that increased Adcy3 activity robustly protect animals from diet-induced metabolic derangements. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1932-6203 |
Relation: | http://europepmc.org/articles/PMC4199629?pdf=render; https://doaj.org/toc/1932-6203 |
DOI: | 10.1371/journal.pone.0110226 |
URL الوصول: | https://doaj.org/article/7afc404eb39b4f2088104b8158864cce |
رقم الأكسشن: | edsdoj.7afc404eb39b4f2088104b8158864cce |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 19326203 |
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DOI: | 10.1371/journal.pone.0110226 |