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The β3 Adrenergic Receptor Agonist CL316243 Ameliorates the Metabolic Abnormalities of High-Fat Diet-Fed Rats by Activating AMPK/PGC-1α Signaling in Skeletal Muscle
PURPOSE: Skeletal muscle has a major influence on whole-body metabolic homeostasis. In the present study, we aimed to determine the metabolic effects of the β3 adrenergic receptor agonist CL316243 (CL) in the skeletal muscle of high-fat diet-fed rats. METHODS: Sprague-Dawley rats were randomly alloc...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987271/ https://www.ncbi.nlm.nih.gov/pubmed/33776460 http://dx.doi.org/10.2147/DMSO.S297351 |
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author | Ding, Li-Na Cheng, Ya Xu, Lu-Yao Zhou, Le-Quan Guan, Li Liu, Hai-Mei Zhang, Ya-Xing Li, Run-Mei Xu, Jin-Wen |
author_facet | Ding, Li-Na Cheng, Ya Xu, Lu-Yao Zhou, Le-Quan Guan, Li Liu, Hai-Mei Zhang, Ya-Xing Li, Run-Mei Xu, Jin-Wen |
author_sort | Ding, Li-Na |
collection | PubMed |
description | PURPOSE: Skeletal muscle has a major influence on whole-body metabolic homeostasis. In the present study, we aimed to determine the metabolic effects of the β3 adrenergic receptor agonist CL316243 (CL) in the skeletal muscle of high-fat diet-fed rats. METHODS: Sprague-Dawley rats were randomly allocated to three groups, which were fed a control diet (C) or a high-fat diet (HF), and half of the latter were administered 1 mg/kg CL by gavage once weekly (HF+CL), for 12 weeks. At the end of this period, the serum lipid profile and glucose tolerance of the rats were evaluated. In addition, the phosphorylation and protein and mRNA expression of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator (PGC)-1α, and carnitine palmitoyl transferase (CPT)-1b in skeletal muscle were measured by Western blot analysis and qPCR. The direct effects of CL on the phosphorylation (p-) and expression of AMPK, PGC-1α, and CPT-1b were also evaluated by Western blotting and immunofluorescence in L6 myotubes. RESULTS: CL administration ameliorated the abnormal lipid profile and glucose tolerance of the high-fat diet-fed rats. In addition, the expression of p-AMPK, PGC-1α, and CPT-1b in the soleus muscle was significantly increased by CL. CL (1 µM) also increased the protein expression of p-AMPK, PGC-1α, and CPT-1b in L6 myotubes. However, the effect of CL on PGC-1α protein expression was blocked by the AMPK antagonist compound C, which suggests that CL increases PGC-1α protein expression via AMPK. CONCLUSION: Activation of the β3 adrenergic receptor in skeletal muscle ameliorates the metabolic abnormalities of high-fat diet-fed rats, at least in part via activation of the AMPK/PGC-1α pathway. |
format | Online Article Text |
id | pubmed-7987271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-79872712021-03-25 The β3 Adrenergic Receptor Agonist CL316243 Ameliorates the Metabolic Abnormalities of High-Fat Diet-Fed Rats by Activating AMPK/PGC-1α Signaling in Skeletal Muscle Ding, Li-Na Cheng, Ya Xu, Lu-Yao Zhou, Le-Quan Guan, Li Liu, Hai-Mei Zhang, Ya-Xing Li, Run-Mei Xu, Jin-Wen Diabetes Metab Syndr Obes Original Research PURPOSE: Skeletal muscle has a major influence on whole-body metabolic homeostasis. In the present study, we aimed to determine the metabolic effects of the β3 adrenergic receptor agonist CL316243 (CL) in the skeletal muscle of high-fat diet-fed rats. METHODS: Sprague-Dawley rats were randomly allocated to three groups, which were fed a control diet (C) or a high-fat diet (HF), and half of the latter were administered 1 mg/kg CL by gavage once weekly (HF+CL), for 12 weeks. At the end of this period, the serum lipid profile and glucose tolerance of the rats were evaluated. In addition, the phosphorylation and protein and mRNA expression of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator (PGC)-1α, and carnitine palmitoyl transferase (CPT)-1b in skeletal muscle were measured by Western blot analysis and qPCR. The direct effects of CL on the phosphorylation (p-) and expression of AMPK, PGC-1α, and CPT-1b were also evaluated by Western blotting and immunofluorescence in L6 myotubes. RESULTS: CL administration ameliorated the abnormal lipid profile and glucose tolerance of the high-fat diet-fed rats. In addition, the expression of p-AMPK, PGC-1α, and CPT-1b in the soleus muscle was significantly increased by CL. CL (1 µM) also increased the protein expression of p-AMPK, PGC-1α, and CPT-1b in L6 myotubes. However, the effect of CL on PGC-1α protein expression was blocked by the AMPK antagonist compound C, which suggests that CL increases PGC-1α protein expression via AMPK. CONCLUSION: Activation of the β3 adrenergic receptor in skeletal muscle ameliorates the metabolic abnormalities of high-fat diet-fed rats, at least in part via activation of the AMPK/PGC-1α pathway. Dove 2021-03-18 /pmc/articles/PMC7987271/ /pubmed/33776460 http://dx.doi.org/10.2147/DMSO.S297351 Text en © 2021 Ding et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Ding, Li-Na Cheng, Ya Xu, Lu-Yao Zhou, Le-Quan Guan, Li Liu, Hai-Mei Zhang, Ya-Xing Li, Run-Mei Xu, Jin-Wen The β3 Adrenergic Receptor Agonist CL316243 Ameliorates the Metabolic Abnormalities of High-Fat Diet-Fed Rats by Activating AMPK/PGC-1α Signaling in Skeletal Muscle |
title | The β3 Adrenergic Receptor Agonist CL316243 Ameliorates the Metabolic Abnormalities of High-Fat Diet-Fed Rats by Activating AMPK/PGC-1α Signaling in Skeletal Muscle |
title_full | The β3 Adrenergic Receptor Agonist CL316243 Ameliorates the Metabolic Abnormalities of High-Fat Diet-Fed Rats by Activating AMPK/PGC-1α Signaling in Skeletal Muscle |
title_fullStr | The β3 Adrenergic Receptor Agonist CL316243 Ameliorates the Metabolic Abnormalities of High-Fat Diet-Fed Rats by Activating AMPK/PGC-1α Signaling in Skeletal Muscle |
title_full_unstemmed | The β3 Adrenergic Receptor Agonist CL316243 Ameliorates the Metabolic Abnormalities of High-Fat Diet-Fed Rats by Activating AMPK/PGC-1α Signaling in Skeletal Muscle |
title_short | The β3 Adrenergic Receptor Agonist CL316243 Ameliorates the Metabolic Abnormalities of High-Fat Diet-Fed Rats by Activating AMPK/PGC-1α Signaling in Skeletal Muscle |
title_sort | β3 adrenergic receptor agonist cl316243 ameliorates the metabolic abnormalities of high-fat diet-fed rats by activating ampk/pgc-1α signaling in skeletal muscle |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987271/ https://www.ncbi.nlm.nih.gov/pubmed/33776460 http://dx.doi.org/10.2147/DMSO.S297351 |
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