The cyclin dependent kinase inhibitor Roscovitine prevents diet-induced metabolic disruption in obese mice
| العنوان: | The cyclin dependent kinase inhibitor Roscovitine prevents diet-induced metabolic disruption in obese mice |
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| المؤلفون: | Nabil Rabhi, Andrew Emili, Stephen R. Farmer, Briana Noel Cortez, Jean Z. Lin, Ryan M. Hekman, Kathleen Desevin |
| المصدر: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) |
| بيانات النشر: | Nature Publishing Group UK, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Science, Lipolysis, Adipose tissue, Fatty acid beta-oxidation, Diet, High-Fat, Second Messenger Systems, Article, Mice, Insulin resistance, Endocrinology, Metabolic Diseases, Cyclin-dependent kinase, Internal medicine, Brown adipose tissue, medicine, Roscovitine, Animals, Obesity, CAMK, Multidisciplinary, biology, Kinase, Chemistry, Endocrine system and metabolic diseases, Thermogenesis, medicine.disease, Cyclin-Dependent Kinases, Insulin receptor, medicine.anatomical_structure, biology.protein, Medicine |
| الوصف: | Most strategies to treat obesity-related disorders have involved prevention of diet-induced weight gain in lean mice. Treatment of obese individuals will require therapies that reverse the detrimental effects of excess body weight. Cyclin-dependent kinases have been shown to contribute to obesity and its adverse complications. Here, we show that roscovitine; a an orally available cyclin-dependent kinase inhibitor; given to male mice during the last six weeks of a 19-week high fat diet, reduced weight gain and prevented accompanying insulin resistance, hepatic steatosis, visceral adipose tissue (eWAT) inflammation/fibrosis as well as restored insulin secretion and enhanced whole body energy expenditure. Proteomics and phosphoproteomics analysis of eWAT demonstrated that roscovitine suppressed expression of peptides and phosphopeptides linked to inflammation and extracellular matrix proteins. It also identified 17 putative protein kinases perturbed by roscovitine, including CMGC kinases, AGC kinases and CAMK kinases. Pathway enrichment analysis showed that lipid metabolism, TCA cycle, fatty acid beta oxidation and creatine biosynthesis are enriched following roscovitine treatment. For brown adipose tissue (BAT), analysis of upstream kinases controlling the phosphoproteome revealed two major kinase groups, AGC and CMGC kinases. Among the top enriched pathways were insulin signaling, regulation of lipolysis in adipocytes, thyroid hormone signaling, thermogenesis and cAMP-PKG signaling. We conclude that roscovitine is effective at preventing prolonged diet-induced metabolic disruption and restoring mitochondrial activity in BAT and eWAT. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::433ae7983fb7479cee7ed65184da91fa http://europepmc.org/articles/PMC8514475 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....433ae7983fb7479cee7ed65184da91fa |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 20452322 |
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