دورية أكاديمية
Targeting negative energy balance with calorie restriction and mitochondrial uncoupling in db/db mice ; Molecular Metabolism
| العنوان: | Targeting negative energy balance with calorie restriction and mitochondrial uncoupling in db/db mice ; Molecular Metabolism |
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| المؤلفون: | Chen, Sing -Young, Beretta, Martina, Olzomer, Ellen M., Shah, Divya P., Wong, Derek Y. H., Alexopoulos, Stephanie J., Aleksovska, Isabella, Salamoun, Joseph M., Garcia, Christopher J., Cochran, Blake J., Rye, Kerry-Anne, Smith, Greg C., Byrne, Frances L., Morris, Margaret J., Santos, Webster L., Cantley, James, Hoehn, Kyle L. |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2023 |
| المجموعة: | VTechWorks (VirginiaTech) |
| مصطلحات موضوعية: | Calorie restriction, Mitochondrial uncoupling, Obesity, Diabetes |
| الوصف: | Objective: Calorie restriction is a first-line treatment for overweight individuals with metabolic impairments. However, few patients can adhere to long-term calorie restriction. An alternative approach to calorie restriction that also causes negative energy balance is mitochondrial uncoupling, which decreases the amount of energy that can be extracted from food. Herein we compare the metabolic effects of calorie restriction with the mitochondrial uncoupler BAM15 in the db/db mouse model of severe hyperglycemia, obesity, hypertriglyceridemia, and fatty liver. Methods: Male db/db mice were treated with w50% calorie restriction, BAM15 at two doses of 0.1% and 0.2% (w/w) admixed in diet, or 0.2% BAM15 with time-restricted feeding from 5 weeks of age. Mice were metabolically phenotyped over 4 weeks with assessment of key readouts including body weight, glucose tolerance, and liver steatosis. At termination, liver tissues were analysed by metabolomics and qPCR. Results: Calorie restriction and high-dose 0.2% BAM15 decreased body weight to a similar extent, but mice treated with BAM15 had far better improvement in glucose control. High-dose BAM15 treatment completely normalized fasting glucose and glucose tolerance to levels similar to lean db/+ control mice. Low-dose 0.1% BAM15 did not affect body mass but partially improved glucose tolerance to a similar degree as 50% calorie restriction. Both calorie restriction and high-dose BAM15 significantly improved hyperglucagonemia and liver and serum triglyceride levels. Combining high-dose BAM15 with time-restricted feeding to match the time that calorie restricted mice were fed resulted in the best metabolic phenotype most similar to lean db/+ controls. BAM15-mediated improvements in glucose control were associated with decreased glucagon levels and decreased expression of enzymes involved in hepatic gluconeogenesis. Conclusions: BAM15 and calorie restriction treatments improved most metabolic disease phenotypes in db/db mice. However, mice fed BAM15 had superior effects ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | 101684; http://hdl.handle.net/10919/114173Test; https://doi.org/10.1016/j.molmet.2023.101684Test; 69 |
| DOI: | 10.1016/j.molmet.2023.101684 |
| الإتاحة: | https://doi.org/10.1016/j.molmet.2023.101684Test http://hdl.handle.net/10919/114173Test |
| حقوق: | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International ; http://creativecommons.org/licenses/by-nc-nd/4.0Test/ |
| رقم الانضمام: | edsbas.DF628F5 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.molmet.2023.101684 |
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