دورية أكاديمية
A neuron-specific deletion of the microRNA-processing enzyme DICER induces severe but transient obesity in mice.
| العنوان: | A neuron-specific deletion of the microRNA-processing enzyme DICER induces severe but transient obesity in mice. |
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| المؤلفون: | Géraldine M Mang, Sylvain Pradervand, Ngoc-Hien Du, Alaaddin Bulak Arpat, Frédéric Preitner, Leonore Wigger, David Gatfield, Paul Franken |
| المصدر: | PLoS ONE, Vol 10, Iss 1, p e0116760 (2015) |
| بيانات النشر: | Public Library of Science (PLoS) |
| سنة النشر: | 2015 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression post-transcriptionally. MiRNAs are implicated in various biological processes associated with obesity, including adipocyte differentiation and lipid metabolism. We used a neuronal-specific inhibition of miRNA maturation in adult mice to study the consequences of miRNA loss on obesity development. Camk2a-CreERT2 (Cre+) and floxed Dicer (Dicerlox/lox) mice were crossed to generate tamoxifen-inducible conditional Dicer knockouts (cKO). Vehicle- and/or tamoxifen-injected Cre+;Dicerlox/lox and Cre+;Dicer+/+ served as controls. Four cohorts were used to a) measure body composition, b) follow food intake and body weight dynamics, c) evaluate basal metabolism and effects of food deprivation, and d) assess the brain transcriptome consequences of miRNA loss. cKO mice developed severe obesity and gained 18 g extra weight over the 5 weeks following tamoxifen injection, mainly due to increased fat mass. This phenotype was highly reproducible and observed in all 38 cKO mice recorded and in none of the controls, excluding possible effects of tamoxifen or the non-induced transgene. Development of obesity was concomitant with hyperphagia, increased food efficiency, and decreased activity. Surprisingly, after reaching maximum body weight, obese cKO mice spontaneously started losing weight as rapidly as it was gained. Weight loss was accompanied by lowered O2-consumption and respiratory-exchange ratio. Brain transcriptome analyses in obese mice identified several obesity-related pathways (e.g. leptin, somatostatin, and nemo-like kinase signaling), as well as genes involved in feeding and appetite (e.g. Pmch, Neurotensin) and in metabolism (e.g. Bmp4, Bmp7, Ptger1, Cox7a1). A gene cluster with anti-correlated expression in the cerebral cortex of post-obese compared to obese mice was enriched for synaptic plasticity pathways. While other studies have identified a role for miRNAs in obesity, we here present a unique model that allows for the study of ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1932-6203 |
| العلاقة: | http://europepmc.org/articles/PMC4309537?pdf=renderTest; https://doaj.org/toc/1932-6203Test; https://doaj.org/article/0e94556c72db4a1cb73c3446bcd3647aTest |
| DOI: | 10.1371/journal.pone.0116760 |
| الإتاحة: | https://doi.org/10.1371/journal.pone.0116760Test https://doaj.org/article/0e94556c72db4a1cb73c3446bcd3647aTest |
| رقم الانضمام: | edsbas.CC9D43B0 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0116760 |