The GPR120 agonist TUG‐891 promotes metabolic health by stimulating mitochondrial respiration in brown fat
| العنوان: | The GPR120 agonist TUG‐891 promotes metabolic health by stimulating mitochondrial respiration in brown fat |
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| المؤلفون: | Geerte Hoeke, Anne Reifel Miller, Patrick C.N. Rensen, Lea H. Dib, Bharat Shimpukade, Trond Ulven, Tamer Coskun, Anthony Okolo, Sander Kooijman, Maaike Schilperoort, Natarin Caengprasath, Mark Christian, Yi-Wah Chan, Aylin C. Hanyaloglu, Andrea D. van Dam, Sami Damak, Isabel M. Mol, Irina G. Shabalina |
| المساهمون: | Biotechnology and Biological Sciences Research Council (BBSRC) |
| المصدر: | EMBO Molecular Medicine EMBO Molecular Medicine, Vol 10, Iss 3, Pp n/a-n/a (2018) EMBO Molecular Medicine, 10(3) Schilperoort, M, van Dam, A D, Hoeke, G, Shabalina, I G, Okolo, A, Hanyaloglu, A C, Dib, L H, Mol, I M, Caengprasath, N, Chan, Y-W, Damak, S, Miller, A R, Coskun, T, Shimpukade, B, Ulven, T, Kooijman, S, Rensen, P C & Christian, M 2018, ' The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial respiration in brown fat ', EMBO Molecular Medicine, vol. 10, no. 3, e8047 . https://doi.org/10.15252/emmm.201708047Test |
| بيانات النشر: | Wiley-Blackwell Publishing Ltd., 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Medicine (General), Ca, GPR120, Adipocytes, White, Gene Expression Regulation/drug effects, Phenylpropionates/pharmacology, QH426-470, Mitochondrion, Receptors, G-Protein-Coupled, Oxygen Consumption/drug effects, Adipose Tissue, Brown, Receptors, G-Protein-Coupled/agonists, Brown adipose tissue, lipid metabolism, Glucose/metabolism, Adipose Tissue, Brown/drug effects, Research Articles, Uncoupling Protein 1, Adiposity, Phenylpropionates, Chemistry, Cell Differentiation, 11 Medical And Health Sciences, Lipids, Mitochondria/drug effects, mitochondria, Ca2+, medicine.anatomical_structure, Adipocytes, Brown, Molecular Medicine, Adipocytes, Brown/cytology, Mitochondrial fission, Oxidation-Reduction, Research Article, Agonist, medicine.medical_specialty, medicine.drug_class, Adipose Tissue, White, Cell Respiration, Adiposity/drug effects, Carbohydrate metabolism, Models, Biological, Adipocytes, White/cytology, 03 medical and health sciences, R5-920, Oxygen Consumption, Adipose Tissue, White/drug effects, Internal medicine, Cell Respiration/drug effects, Genetics, medicine, Animals, Body Weight/drug effects, Pharmacology & Drug Discovery, Biphenyl Compounds, Body Weight, Uncoupling Protein 1/metabolism, Lipid metabolism, brown adipose tissue, 06 Biological Sciences, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Metabolism, Glucose, Gene Expression Regulation, Cell Differentiation/drug effects, Biphenyl Compounds/pharmacology, Thermogenesis, RC |
| الوصف: | Brown adipose tissue (BAT) activation stimulates energy expenditure in human adults, which makes it an attractive target to combat obesity and related disorders. Recent studies demonstrated a role for G protein‐coupled receptor 120 (GPR120) in BAT thermogenesis. Here, we investigated the therapeutic potential of GPR120 agonism and addressed GPR120‐mediated signaling in BAT. We found that activation of GPR120 by the selective agonist TUG‐891 acutely increases fat oxidation and reduces body weight and fat mass in C57Bl/6J mice. These effects coincided with decreased brown adipocyte lipid content and increased nutrient uptake by BAT, confirming increased BAT activity. Consistent with these observations, GPR120 deficiency reduced expression of genes involved in nutrient handling in BAT. Stimulation of brown adipocytes in vitro with TUG‐891 acutely induced O 2 consumption, through GPR120‐dependent and GPR120‐independent mechanisms. TUG‐891 not only stimulated GPR120 signaling resulting in intracellular calcium release, mitochondrial depolarization, and mitochondrial fission, but also activated UCP1. Collectively, these data suggest that activation of brown adipocytes with the GPR120 agonist TUG‐891 is a promising strategy to increase lipid combustion and reduce obesity. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1757-4676 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e500a414f38fbfef93af89f8a97f0493Test http://wrap.warwick.ac.uk/97936/1/GPR120-agonist-TUG-391-promotes-Christian-2018.pdfTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e500a414f38fbfef93af89f8a97f0493 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17574676 |
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