Rutaecarpine Promotes Adipose Thermogenesis and Protects against HFD-Induced Obesity via AMPK/PGC-1α Pathway
Pharmacological activation of adaptive thermogenesis to increase energy expenditure is considered to be a novel strategy for obesity. Peroxisome-proliferator-activated receptor γ co-activator-1α (PGC-1α), which serves as an inducible co-activator in energy expenditure, is highly expressed in brown a...
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MDPI AG
2022-04-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/4/469 |
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| author | Dandan Chen Yanan Duan Shuxiang Yu Xinwen Zhang Ni Li Jingya Li |
| author_facet | Dandan Chen Yanan Duan Shuxiang Yu Xinwen Zhang Ni Li Jingya Li |
| author_sort | Dandan Chen |
| collection | DOAJ |
| description | Pharmacological activation of adaptive thermogenesis to increase energy expenditure is considered to be a novel strategy for obesity. Peroxisome-proliferator-activated receptor γ co-activator-1α (PGC-1α), which serves as an inducible co-activator in energy expenditure, is highly expressed in brown adipose tissues (BAT). In this study, we found a PGC-1α transcriptional activator, natural compound rutaecarpine (Rut), which promoted brown adipocytes mitochondrial biogenesis and thermogenesis in vitro. Chronic Rut treatment reduced the body weight gain and mitigated insulin sensitivity through brown and beige adipocyte thermogenesis. Mechanistic study showed that Rut activated the energy metabolic pathway AMP-activated protein kinase (AMPK)/PGC-1α axis, and deficiency of AMPK abolished the beneficial metabolic phenotype of the Rut treatment in vitro and in vivo. In summary, a PGC-1α transcriptional activator Rut was found to activate brown and beige adipose thermogenesis to resist diet-induced obesity through AMPK pathway. Our findings serve as a further understanding of the natural compound in adipose tissue and provides a possible strategy to combat obesity and related metabolic disorders. |
| first_indexed | 2024-03-09T13:09:40Z |
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| id | doaj.art-7ce30957a6dd41839eccb42a4fb3aed1 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T13:09:40Z |
| publishDate | 2022-04-01 |
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| series | Pharmaceuticals |
| spelling | doaj.art-7ce30957a6dd41839eccb42a4fb3aed12023-11-30T21:43:15ZengMDPI AGPharmaceuticals1424-82472022-04-0115446910.3390/ph15040469Rutaecarpine Promotes Adipose Thermogenesis and Protects against HFD-Induced Obesity via AMPK/PGC-1α PathwayDandan Chen0Yanan Duan1Shuxiang Yu2Xinwen Zhang3Ni Li4Jingya Li5School of Life Sciences, Shanghai University, Shanghai 200444, ChinaState Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaSchool of Life Sciences, Shanghai University, Shanghai 200444, ChinaState Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaState Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaState Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaPharmacological activation of adaptive thermogenesis to increase energy expenditure is considered to be a novel strategy for obesity. Peroxisome-proliferator-activated receptor γ co-activator-1α (PGC-1α), which serves as an inducible co-activator in energy expenditure, is highly expressed in brown adipose tissues (BAT). In this study, we found a PGC-1α transcriptional activator, natural compound rutaecarpine (Rut), which promoted brown adipocytes mitochondrial biogenesis and thermogenesis in vitro. Chronic Rut treatment reduced the body weight gain and mitigated insulin sensitivity through brown and beige adipocyte thermogenesis. Mechanistic study showed that Rut activated the energy metabolic pathway AMP-activated protein kinase (AMPK)/PGC-1α axis, and deficiency of AMPK abolished the beneficial metabolic phenotype of the Rut treatment in vitro and in vivo. In summary, a PGC-1α transcriptional activator Rut was found to activate brown and beige adipose thermogenesis to resist diet-induced obesity through AMPK pathway. Our findings serve as a further understanding of the natural compound in adipose tissue and provides a possible strategy to combat obesity and related metabolic disorders.https://www.mdpi.com/1424-8247/15/4/469obesityrutaecarpineadipocytesthermogenesisperoxisome-proliferator-activated receptor γ co-activator-1αAMP-activated protein kinase |
| spellingShingle | Dandan Chen Yanan Duan Shuxiang Yu Xinwen Zhang Ni Li Jingya Li Rutaecarpine Promotes Adipose Thermogenesis and Protects against HFD-Induced Obesity via AMPK/PGC-1α Pathway Pharmaceuticals obesity rutaecarpine adipocytes thermogenesis peroxisome-proliferator-activated receptor γ co-activator-1α AMP-activated protein kinase |
| title | Rutaecarpine Promotes Adipose Thermogenesis and Protects against HFD-Induced Obesity via AMPK/PGC-1α Pathway |
| title_full | Rutaecarpine Promotes Adipose Thermogenesis and Protects against HFD-Induced Obesity via AMPK/PGC-1α Pathway |
| title_fullStr | Rutaecarpine Promotes Adipose Thermogenesis and Protects against HFD-Induced Obesity via AMPK/PGC-1α Pathway |
| title_full_unstemmed | Rutaecarpine Promotes Adipose Thermogenesis and Protects against HFD-Induced Obesity via AMPK/PGC-1α Pathway |
| title_short | Rutaecarpine Promotes Adipose Thermogenesis and Protects against HFD-Induced Obesity via AMPK/PGC-1α Pathway |
| title_sort | rutaecarpine promotes adipose thermogenesis and protects against hfd induced obesity via ampk pgc 1α pathway |
| topic | obesity rutaecarpine adipocytes thermogenesis peroxisome-proliferator-activated receptor γ co-activator-1α AMP-activated protein kinase |
| url | https://www.mdpi.com/1424-8247/15/4/469 |
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