دورية أكاديمية
Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance
| العنوان: | Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance |
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| المؤلفون: | Hwang, M., Go, Y., Park, J-H, Shin, S-K, Song, S. E., Oh, B-C, Im, S-S, Hwang, I., Jeon, Y. H., Lee, I-K, Seino, S., Song, D-K |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2018 |
| المجموعة: | Kobe University Repository (Kernel) / 神戸大学学術成果リポジトリ |
| الوصف: | BACKGROUND: The exchange protein directly activated by cAMP (Epac), which is primarily involved in cAMP signaling, has been known to be essential for controlling body energy metabolism. Epac has two isoforms: Epac1 and Epac2. The function of Epac1 on obesity was unveiled using Epac1 knockout (KO) mice. However, the role of Epac2 in obesity remains unclear. METHODS: To evaluate the role of Epac2 in obesity, we used Epac2a KO mice, which is dominantly expressed in neurons and endocrine tissues. Physiological factors related to obesity were analyzed: body weight, fat mass, food intake, plasma leptin and adiponectin levels, energy expenditure, glucose tolerance, and insulin and leptin resistance. To determine the mechanism of Epac2a, mice received exogenous leptin and then hypothalamic leptin signaling was analyzed. RESULTS: Epac2a KO mice appeared to have normal glucose tolerance and insulin sensitivity until 12 weeks of age, but an early onset increase of plasma leptin levels and decrease of plasma adiponectin levels compared with wild-type mice. Acute leptin injection revealed impaired hypothalamic leptin signaling in KO mice. Consistently, KO mice fed a high-fat diet (HFD) were significantly obese, presenting greater food intake and lower energy expenditure. HFD-fed KO mice were also characterized by greater impairment of hypothalamic leptin signaling and by weaker leptin-induced decrease in food consumption compared with HFD-fed wild-type mice. In wild-type mice, acute exogenous leptin injection or chronic HFD feeding tended to induce hypothalamic Epac2a expression. CONCLUSIONS: Considering that HFD is an inducer of hypothalamic leptin resistance and that Epac2a functions in pancreatic beta cells during demands of greater work load, hypothalamic Epac2a may have a role in facilitating leptin signaling, at least in response to higher metabolic demands. Thus, our data indicate that Epac2a is critical for preventing obesity and thus Epac2a activators may be used to manage obesity and obesity-mediated metabolic disorders. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:doi/10.1038/ijo.2016.208 |
| الإتاحة: | http://www.lib.kobe-u.ac.jp/handle_kernel/90004550Test http://www.lib.kobe-u.ac.jp/repository/90004550.pdfTest |
| حقوق: | © The Author(s) 2017 This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if thematerial is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0Test/ |
| رقم الانضمام: | edsbas.ED102768 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |