Early intervention of baicalin suppresses obesity-induced adipose tissue fibrotic remodeling through Interfering NF-κB/HIF-1ɑ/GRK2 Signaling Pathway
Obesity-induced adipose tissue (AT) fibrosis is difficult to reverse, indicating the importance of early intervention. G protein-coupled receptor kinase 2 (GRK2) is a potential regulator of energy metabolism. Baicalin can improve insulin sensitivity and metabolic homeostasis. However, their impacts...
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Elsevier
2025-08-01
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| Series: | Phytomedicine Plus |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667031325000879 |
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| author | Ying Zeng Wenting Li Tingting Ma Honglei Zhang Jiaxing Xu Kang Liu |
| author_facet | Ying Zeng Wenting Li Tingting Ma Honglei Zhang Jiaxing Xu Kang Liu |
| author_sort | Ying Zeng |
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| description | Obesity-induced adipose tissue (AT) fibrosis is difficult to reverse, indicating the importance of early intervention. G protein-coupled receptor kinase 2 (GRK2) is a potential regulator of energy metabolism. Baicalin can improve insulin sensitivity and metabolic homeostasis. However, their impacts on AT fibrosis have not been deciphered. This study aims to uncover the influence of early baicalin intervention on GRK2-related AT fibrotic remodeling under lipid overload. Mice were fed a high-fat diet (HFD) for 8 weeks and received baicalin or metformin during the whole period. 3T3-L1 adipocytes were pre-treated with baicalin, metformin, or pharmacological inhibitors before exposure to palmitic acid (PA) or hypoxia for 20 h. Sometimes, Cells were transfected with siRNA or plasmid DNA specific for GRK2. Results showed that increased GRK2 in AT was observed early after HFD feeding. GRK2 silencing in adipocytes attenuated the profibrotic activation and improved insulin sensitivity and adipokine secretion, but GRK2 overexpression had the opposite effect. Baicalin treatment resulted in the downregulation of GRK2 in 3T3-L1 adipocytes and epididymal AT from the early stage after lipid overload, prevented the profibrotic response, and ameliorated systemic and local insulin resistance. In addition, the negative regulation of GRK2 by baicalin was associated with reduced NF-κB phosphorylation and HIF-1ɑ abundance. Collectively, baicalin prevents HFD-induced AT fibrosis and ameliorates insulin resistance by interfering NF-κB/HIF-1ɑ/GRK2 signaling pathway. This finding provides a better insight into the regulatory effect of baicalin on AT homeostasis and reinforces its promising role in managing obesity-related diseases. |
| format | Article |
| id | doaj-art-558ad03adf6248138708fc8a5607f9bb |
| institution | Kabale University |
| issn | 2667-0313 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
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| series | Phytomedicine Plus |
| spelling | doaj-art-558ad03adf6248138708fc8a5607f9bb2025-08-21T04:17:25ZengElsevierPhytomedicine Plus2667-03132025-08-015310081510.1016/j.phyplu.2025.100815Early intervention of baicalin suppresses obesity-induced adipose tissue fibrotic remodeling through Interfering NF-κB/HIF-1ɑ/GRK2 Signaling PathwayYing Zeng0Wenting Li1Tingting Ma2Honglei Zhang3Jiaxing Xu4Kang Liu5Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, PR China; Sunshine Lake Pharma Co., Ltd., 368 Middle Zhenan Road, Changan, Dongguan, Guangdong, PR ChinaDepartment of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, PR ChinaDepartment of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, PR China; Guoyang Hospital of Traditional Chinese Medicine, 500 Zhabei Road, Guoyang, Bozhou, 233600, PR ChinaDepartment of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, PR ChinaDepartment of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, PR ChinaDepartment of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, PR China; Corresponding authors at: Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China,Obesity-induced adipose tissue (AT) fibrosis is difficult to reverse, indicating the importance of early intervention. G protein-coupled receptor kinase 2 (GRK2) is a potential regulator of energy metabolism. Baicalin can improve insulin sensitivity and metabolic homeostasis. However, their impacts on AT fibrosis have not been deciphered. This study aims to uncover the influence of early baicalin intervention on GRK2-related AT fibrotic remodeling under lipid overload. Mice were fed a high-fat diet (HFD) for 8 weeks and received baicalin or metformin during the whole period. 3T3-L1 adipocytes were pre-treated with baicalin, metformin, or pharmacological inhibitors before exposure to palmitic acid (PA) or hypoxia for 20 h. Sometimes, Cells were transfected with siRNA or plasmid DNA specific for GRK2. Results showed that increased GRK2 in AT was observed early after HFD feeding. GRK2 silencing in adipocytes attenuated the profibrotic activation and improved insulin sensitivity and adipokine secretion, but GRK2 overexpression had the opposite effect. Baicalin treatment resulted in the downregulation of GRK2 in 3T3-L1 adipocytes and epididymal AT from the early stage after lipid overload, prevented the profibrotic response, and ameliorated systemic and local insulin resistance. In addition, the negative regulation of GRK2 by baicalin was associated with reduced NF-κB phosphorylation and HIF-1ɑ abundance. Collectively, baicalin prevents HFD-induced AT fibrosis and ameliorates insulin resistance by interfering NF-κB/HIF-1ɑ/GRK2 signaling pathway. This finding provides a better insight into the regulatory effect of baicalin on AT homeostasis and reinforces its promising role in managing obesity-related diseases.http://www.sciencedirect.com/science/article/pii/S2667031325000879BaicalinGRK2ObesityAdipose tissue fibrosisNF-κBHIF-1ɑ |
| spellingShingle | Ying Zeng Wenting Li Tingting Ma Honglei Zhang Jiaxing Xu Kang Liu Early intervention of baicalin suppresses obesity-induced adipose tissue fibrotic remodeling through Interfering NF-κB/HIF-1ɑ/GRK2 Signaling Pathway Phytomedicine Plus Baicalin GRK2 Obesity Adipose tissue fibrosis NF-κB HIF-1ɑ |
| title | Early intervention of baicalin suppresses obesity-induced adipose tissue fibrotic remodeling through Interfering NF-κB/HIF-1ɑ/GRK2 Signaling Pathway |
| title_full | Early intervention of baicalin suppresses obesity-induced adipose tissue fibrotic remodeling through Interfering NF-κB/HIF-1ɑ/GRK2 Signaling Pathway |
| title_fullStr | Early intervention of baicalin suppresses obesity-induced adipose tissue fibrotic remodeling through Interfering NF-κB/HIF-1ɑ/GRK2 Signaling Pathway |
| title_full_unstemmed | Early intervention of baicalin suppresses obesity-induced adipose tissue fibrotic remodeling through Interfering NF-κB/HIF-1ɑ/GRK2 Signaling Pathway |
| title_short | Early intervention of baicalin suppresses obesity-induced adipose tissue fibrotic remodeling through Interfering NF-κB/HIF-1ɑ/GRK2 Signaling Pathway |
| title_sort | early intervention of baicalin suppresses obesity induced adipose tissue fibrotic remodeling through interfering nf κb hif 1ɑ grk2 signaling pathway |
| topic | Baicalin GRK2 Obesity Adipose tissue fibrosis NF-κB HIF-1ɑ |
| url | http://www.sciencedirect.com/science/article/pii/S2667031325000879 |
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