Fuziline Ameliorates Glucose and Lipid Metabolism by Activating Beta Adrenergic Receptors to Stimulate Thermogenesis
<i>Radix aconiti carmichaeli</i> is a widely used traditional Chinese medicine that has been found to be effective in treating cardiovascular diseases and metabolic disorders. Patients with these diseases often experience a heat generation disorder, which is characterized by chilliness a...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/9/8362 |
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| author | He Gao Zhenqiang Li Chuanjing Cheng Jing Cui Jiamin Peng Xiaoying Wang Man Zhang Yuanyuan Hou Gang Bai |
| author_facet | He Gao Zhenqiang Li Chuanjing Cheng Jing Cui Jiamin Peng Xiaoying Wang Man Zhang Yuanyuan Hou Gang Bai |
| author_sort | He Gao |
| collection | DOAJ |
| description | <i>Radix aconiti carmichaeli</i> is a widely used traditional Chinese medicine that has been found to be effective in treating cardiovascular diseases and metabolic disorders. Patients with these diseases often experience a heat generation disorder, which is characterized by chilliness and can worsen the progression of the disease. This study established an in vitro screening model combining the examination of cellular mitochondrial membrane potential and mitochondrial temperature to screen drugs with thermogenic activity. After differentiation and determination of the content of characteristic metabolites of the drug-containing serum blood components, it was found that Fuziline (FZL) is the key thermogenic property in <i>Radix aconiti carmichaeli</i>, responsible for its thermogenic effects with a high relative importance of 33%. Experiments were conducted to evaluate the thermogenic activity of <i>Radix aconiti carmichaeli</i> and FZL in vivo by assessing temperature changes in various organs, including the rectum, liver, and brown adipose tissue. Moreover, the effects of intracellular β<sub>3</sub>-adrenergic receptor (β<sub>3</sub>-AR) agonistic effects were evaluated using transient β<sub>3</sub>-AR transfection and dual-luciferase assay systems. The molecular mechanism by which FZL promotes thermogenesis and improves mitochondrial function was investigated by verifying the β-adrenergic receptors (β-AR) downstream signaling pathway. The results suggest that FZL activates β-AR nonselectively, which in turn activates the downstream cAMP-PKA signaling pathway and leads to an increase in liver glycogenolysis and triglyceride hydrolysis, accompanied by enhancing mitochondrial energy metabolism. Consequently, the liver and brown adipose tissue receive energy to generate heat. In summary, these findings provide insight into the therapeutic application of <i>Radix aconiti carmichaeli</i> for metabolic disorders associated with heat generation disorders. |
| first_indexed | 2024-03-11T04:15:47Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:15:47Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-01b41aeb514643d5847540321a14d7d62023-11-17T23:08:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-01249836210.3390/ijms24098362Fuziline Ameliorates Glucose and Lipid Metabolism by Activating Beta Adrenergic Receptors to Stimulate ThermogenesisHe Gao0Zhenqiang Li1Chuanjing Cheng2Jing Cui3Jiamin Peng4Xiaoying Wang5Man Zhang6Yuanyuan Hou7Gang Bai8State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaSchool of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China<i>Radix aconiti carmichaeli</i> is a widely used traditional Chinese medicine that has been found to be effective in treating cardiovascular diseases and metabolic disorders. Patients with these diseases often experience a heat generation disorder, which is characterized by chilliness and can worsen the progression of the disease. This study established an in vitro screening model combining the examination of cellular mitochondrial membrane potential and mitochondrial temperature to screen drugs with thermogenic activity. After differentiation and determination of the content of characteristic metabolites of the drug-containing serum blood components, it was found that Fuziline (FZL) is the key thermogenic property in <i>Radix aconiti carmichaeli</i>, responsible for its thermogenic effects with a high relative importance of 33%. Experiments were conducted to evaluate the thermogenic activity of <i>Radix aconiti carmichaeli</i> and FZL in vivo by assessing temperature changes in various organs, including the rectum, liver, and brown adipose tissue. Moreover, the effects of intracellular β<sub>3</sub>-adrenergic receptor (β<sub>3</sub>-AR) agonistic effects were evaluated using transient β<sub>3</sub>-AR transfection and dual-luciferase assay systems. The molecular mechanism by which FZL promotes thermogenesis and improves mitochondrial function was investigated by verifying the β-adrenergic receptors (β-AR) downstream signaling pathway. The results suggest that FZL activates β-AR nonselectively, which in turn activates the downstream cAMP-PKA signaling pathway and leads to an increase in liver glycogenolysis and triglyceride hydrolysis, accompanied by enhancing mitochondrial energy metabolism. Consequently, the liver and brown adipose tissue receive energy to generate heat. In summary, these findings provide insight into the therapeutic application of <i>Radix aconiti carmichaeli</i> for metabolic disorders associated with heat generation disorders.https://www.mdpi.com/1422-0067/24/9/8362<i>Radix aconiti carmichaeli</i>fuzilinethermogenesisbeta adrenergic receptors |
| spellingShingle | He Gao Zhenqiang Li Chuanjing Cheng Jing Cui Jiamin Peng Xiaoying Wang Man Zhang Yuanyuan Hou Gang Bai Fuziline Ameliorates Glucose and Lipid Metabolism by Activating Beta Adrenergic Receptors to Stimulate Thermogenesis International Journal of Molecular Sciences <i>Radix aconiti carmichaeli</i> fuziline thermogenesis beta adrenergic receptors |
| title | Fuziline Ameliorates Glucose and Lipid Metabolism by Activating Beta Adrenergic Receptors to Stimulate Thermogenesis |
| title_full | Fuziline Ameliorates Glucose and Lipid Metabolism by Activating Beta Adrenergic Receptors to Stimulate Thermogenesis |
| title_fullStr | Fuziline Ameliorates Glucose and Lipid Metabolism by Activating Beta Adrenergic Receptors to Stimulate Thermogenesis |
| title_full_unstemmed | Fuziline Ameliorates Glucose and Lipid Metabolism by Activating Beta Adrenergic Receptors to Stimulate Thermogenesis |
| title_short | Fuziline Ameliorates Glucose and Lipid Metabolism by Activating Beta Adrenergic Receptors to Stimulate Thermogenesis |
| title_sort | fuziline ameliorates glucose and lipid metabolism by activating beta adrenergic receptors to stimulate thermogenesis |
| topic | <i>Radix aconiti carmichaeli</i> fuziline thermogenesis beta adrenergic receptors |
| url | https://www.mdpi.com/1422-0067/24/9/8362 |
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