The GPR120 agonist TUG‐891 promotes metabolic health by stimulating mitochondrial respiration in brown fat
Abstract 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 th...
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| Format: | Article |
| Language: | English |
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Springer Nature
2018-01-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201708047 |
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| author | Maaike Schilperoort Andrea D van Dam Geerte Hoeke Irina G Shabalina Anthony Okolo Aylin C Hanyaloglu Lea H Dib Isabel M Mol Natarin Caengprasath Yi‐Wah Chan Sami Damak Anne Reifel Miller Tamer Coskun Bharat Shimpukade Trond Ulven Sander Kooijman Patrick CN Rensen Mark Christian |
| author_facet | Maaike Schilperoort Andrea D van Dam Geerte Hoeke Irina G Shabalina Anthony Okolo Aylin C Hanyaloglu Lea H Dib Isabel M Mol Natarin Caengprasath Yi‐Wah Chan Sami Damak Anne Reifel Miller Tamer Coskun Bharat Shimpukade Trond Ulven Sander Kooijman Patrick CN Rensen Mark Christian |
| author_sort | Maaike Schilperoort |
| collection | DOAJ |
| description | Abstract 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 O2 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. |
| format | Article |
| id | doaj-art-435be6144c2f46c4be6f9f0833c44ebc |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-435be6144c2f46c4be6f9f0833c44ebc2025-08-20T04:03:07ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842018-01-0110311810.15252/emmm.201708047The GPR120 agonist TUG‐891 promotes metabolic health by stimulating mitochondrial respiration in brown fatMaaike Schilperoort0Andrea D van Dam1Geerte Hoeke2Irina G Shabalina3Anthony Okolo4Aylin C Hanyaloglu5Lea H Dib6Isabel M Mol7Natarin Caengprasath8Yi‐Wah Chan9Sami Damak10Anne Reifel Miller11Tamer Coskun12Bharat Shimpukade13Trond Ulven14Sander Kooijman15Patrick CN Rensen16Mark Christian17Division of Biomedical Sciences, Warwick Medical School, University of WarwickDivision of Endocrinology, Department of Medicine, Leiden University Medical CenterDivision of Endocrinology, Department of Medicine, Leiden University Medical CenterDepartment of Molecular Biosciences, The Wenner‐Gren Institute, The Arrhenius Laboratories F3, Stockholm UniversityDepartment of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College LondonDepartment of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College LondonInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of BirminghamDivision of Endocrinology, Department of Medicine, Leiden University Medical CenterDepartment of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College LondonLymphocyte Development Group, MRC London Institute of Medical Sciences, Hammersmith Campus, Imperial College LondonNestlé Research CenterLilly Research Laboratories, Diabetes/Endocrine Department, Lilly Corporate CenterLilly Research Laboratories, Diabetes/Endocrine Department, Lilly Corporate CenterDepartment of Physics, Chemistry and Pharmacy, University of Southern DenmarkDepartment of Physics, Chemistry and Pharmacy, University of Southern DenmarkDivision of Endocrinology, Department of Medicine, Leiden University Medical CenterDivision of Endocrinology, Department of Medicine, Leiden University Medical CenterDivision of Biomedical Sciences, Warwick Medical School, University of WarwickAbstract 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 O2 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.https://doi.org/10.15252/emmm.201708047brown adipose tissueCa2+GPR120lipid metabolismmitochondria |
| spellingShingle | Maaike Schilperoort Andrea D van Dam Geerte Hoeke Irina G Shabalina Anthony Okolo Aylin C Hanyaloglu Lea H Dib Isabel M Mol Natarin Caengprasath Yi‐Wah Chan Sami Damak Anne Reifel Miller Tamer Coskun Bharat Shimpukade Trond Ulven Sander Kooijman Patrick CN Rensen Mark Christian The GPR120 agonist TUG‐891 promotes metabolic health by stimulating mitochondrial respiration in brown fat EMBO Molecular Medicine brown adipose tissue Ca2+ GPR120 lipid metabolism mitochondria |
| title | The GPR120 agonist TUG‐891 promotes metabolic health by stimulating mitochondrial respiration in brown fat |
| title_full | The GPR120 agonist TUG‐891 promotes metabolic health by stimulating mitochondrial respiration in brown fat |
| title_fullStr | The GPR120 agonist TUG‐891 promotes metabolic health by stimulating mitochondrial respiration in brown fat |
| title_full_unstemmed | The GPR120 agonist TUG‐891 promotes metabolic health by stimulating mitochondrial respiration in brown fat |
| title_short | The GPR120 agonist TUG‐891 promotes metabolic health by stimulating mitochondrial respiration in brown fat |
| title_sort | gpr120 agonist tug 891 promotes metabolic health by stimulating mitochondrial respiration in brown fat |
| topic | brown adipose tissue Ca2+ GPR120 lipid metabolism mitochondria |
| url | https://doi.org/10.15252/emmm.201708047 |
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