Glucagon-like Peptide-1 Improves Fatty Liver and Enhances Thermogenesis in Brown Adipose Tissue via Inhibiting BMP4-Related Signaling Pathway in High-Fat-Diet-Induced Obese Mice
Objective. Glucagon-like peptide-1 (GLP-1) receptor agonist is effective in decreasing blood glucose and body weight. It could improve fatty liver with unclear mechanisms. Hence, we aimed to explore whether GLP-1 could improve fatty liver by regulating the BMP4-related signaling pathway. Methods. Fi...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-01-01
|
| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2021/6620289 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849304860789309440 |
|---|---|
| author | Xingchun Wang Bingwei Ma Jiaqi Chen Hui You Chunjun Sheng Peng Yang Shen Qu |
| author_facet | Xingchun Wang Bingwei Ma Jiaqi Chen Hui You Chunjun Sheng Peng Yang Shen Qu |
| author_sort | Xingchun Wang |
| collection | DOAJ |
| description | Objective. Glucagon-like peptide-1 (GLP-1) receptor agonist is effective in decreasing blood glucose and body weight. It could improve fatty liver with unclear mechanisms. Hence, we aimed to explore whether GLP-1 could improve fatty liver by regulating the BMP4-related signaling pathway. Methods. Fifteen C57BL/6 mice were randomly assigned to 3 groups. Group A and Group B were fed with a high-fat diet (HFD) to induce fatty liver while Group C was fed with a regular diet (RD) for 24 weeks. Group A and Group B received a subcutaneous injection of exenatide and vehicle (0.9% NaCl), respectively, once daily at doses of 10 nmol/kg during the last 8 weeks. Bodyweight, liver weight, and lipid levels were measured. Histological analyses of liver tissue were performed. The expression of protein and gene measured by western blotting and real-time polymerase chain reaction (RT-PCR) was compared. Results. Eight-week exenatide treatment significantly decreased body weight in Group A (from 44.08 ± 2.89 g to 39.22 ± 1.88 g, P = 0.045). Group A had lower body weight and liver weight than Group B at 24 weeks (39.22 ± 1.88 g vs. 47.34 ± 2.43 g, P = 0.001 and 1.70 ± 0.20 g vs. 2.48 ± 0.19 g, P = 0.001, respectively). Moreover, Group A showed significantly less liver steatosis than Group B. Additionally, Group A led to slightly decreased serum triglyceride (TG) and cholesterol (TC) levels compared to Group B. Western blotting showed that exenatide could prevent HFD-induced upregulation of BMP4 levels and downstream activation of Smad1/5/8 and the P38 MAPK signaling pathway in the liver. Furthermore, exenatide treatment could reduce BMP4 and enhance UCP-1 (an important thermogenin) in brown adipose tissue (BAT). Conclusion. Exenatide could improve HFD-induced hepatic steatosis and enhance thermogenesis in BAT, which may be partly attributed to the inhibition of the BMP4-related signaling pathway. |
| format | Article |
| id | doaj-art-3fea84d2f75d4cde90dfbcb1fb52850d |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-3fea84d2f75d4cde90dfbcb1fb52850d2025-08-20T03:55:36ZengWileyInternational Journal of Endocrinology1687-83371687-83452021-01-01202110.1155/2021/66202896620289Glucagon-like Peptide-1 Improves Fatty Liver and Enhances Thermogenesis in Brown Adipose Tissue via Inhibiting BMP4-Related Signaling Pathway in High-Fat-Diet-Induced Obese MiceXingchun Wang0Bingwei Ma1Jiaqi Chen2Hui You3Chunjun Sheng4Peng Yang5Shen Qu6Thyriod Research Center of Shanghai, Shanghai Tenth People’s Hospital of Tongji University, School of Medicine, Tongji University, Shanghai 200072, ChinaDepartment of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital of Tongji University, School of Medicine, Tongji University, Shanghai 200072, ChinaSuzhou Municipal Hospital, Suzhou 215000, Jiangsu, ChinaDepartment of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital of Tongji University, School of Medicine, Tongji University, Shanghai 200072, ChinaThyriod Research Center of Shanghai, Shanghai Tenth People’s Hospital of Tongji University, School of Medicine, Tongji University, Shanghai 200072, ChinaThyriod Research Center of Shanghai, Shanghai Tenth People’s Hospital of Tongji University, School of Medicine, Tongji University, Shanghai 200072, ChinaThyriod Research Center of Shanghai, Shanghai Tenth People’s Hospital of Tongji University, School of Medicine, Tongji University, Shanghai 200072, ChinaObjective. Glucagon-like peptide-1 (GLP-1) receptor agonist is effective in decreasing blood glucose and body weight. It could improve fatty liver with unclear mechanisms. Hence, we aimed to explore whether GLP-1 could improve fatty liver by regulating the BMP4-related signaling pathway. Methods. Fifteen C57BL/6 mice were randomly assigned to 3 groups. Group A and Group B were fed with a high-fat diet (HFD) to induce fatty liver while Group C was fed with a regular diet (RD) for 24 weeks. Group A and Group B received a subcutaneous injection of exenatide and vehicle (0.9% NaCl), respectively, once daily at doses of 10 nmol/kg during the last 8 weeks. Bodyweight, liver weight, and lipid levels were measured. Histological analyses of liver tissue were performed. The expression of protein and gene measured by western blotting and real-time polymerase chain reaction (RT-PCR) was compared. Results. Eight-week exenatide treatment significantly decreased body weight in Group A (from 44.08 ± 2.89 g to 39.22 ± 1.88 g, P = 0.045). Group A had lower body weight and liver weight than Group B at 24 weeks (39.22 ± 1.88 g vs. 47.34 ± 2.43 g, P = 0.001 and 1.70 ± 0.20 g vs. 2.48 ± 0.19 g, P = 0.001, respectively). Moreover, Group A showed significantly less liver steatosis than Group B. Additionally, Group A led to slightly decreased serum triglyceride (TG) and cholesterol (TC) levels compared to Group B. Western blotting showed that exenatide could prevent HFD-induced upregulation of BMP4 levels and downstream activation of Smad1/5/8 and the P38 MAPK signaling pathway in the liver. Furthermore, exenatide treatment could reduce BMP4 and enhance UCP-1 (an important thermogenin) in brown adipose tissue (BAT). Conclusion. Exenatide could improve HFD-induced hepatic steatosis and enhance thermogenesis in BAT, which may be partly attributed to the inhibition of the BMP4-related signaling pathway.http://dx.doi.org/10.1155/2021/6620289 |
| spellingShingle | Xingchun Wang Bingwei Ma Jiaqi Chen Hui You Chunjun Sheng Peng Yang Shen Qu Glucagon-like Peptide-1 Improves Fatty Liver and Enhances Thermogenesis in Brown Adipose Tissue via Inhibiting BMP4-Related Signaling Pathway in High-Fat-Diet-Induced Obese Mice International Journal of Endocrinology |
| title | Glucagon-like Peptide-1 Improves Fatty Liver and Enhances Thermogenesis in Brown Adipose Tissue via Inhibiting BMP4-Related Signaling Pathway in High-Fat-Diet-Induced Obese Mice |
| title_full | Glucagon-like Peptide-1 Improves Fatty Liver and Enhances Thermogenesis in Brown Adipose Tissue via Inhibiting BMP4-Related Signaling Pathway in High-Fat-Diet-Induced Obese Mice |
| title_fullStr | Glucagon-like Peptide-1 Improves Fatty Liver and Enhances Thermogenesis in Brown Adipose Tissue via Inhibiting BMP4-Related Signaling Pathway in High-Fat-Diet-Induced Obese Mice |
| title_full_unstemmed | Glucagon-like Peptide-1 Improves Fatty Liver and Enhances Thermogenesis in Brown Adipose Tissue via Inhibiting BMP4-Related Signaling Pathway in High-Fat-Diet-Induced Obese Mice |
| title_short | Glucagon-like Peptide-1 Improves Fatty Liver and Enhances Thermogenesis in Brown Adipose Tissue via Inhibiting BMP4-Related Signaling Pathway in High-Fat-Diet-Induced Obese Mice |
| title_sort | glucagon like peptide 1 improves fatty liver and enhances thermogenesis in brown adipose tissue via inhibiting bmp4 related signaling pathway in high fat diet induced obese mice |
| url | http://dx.doi.org/10.1155/2021/6620289 |
| work_keys_str_mv | AT xingchunwang glucagonlikepeptide1improvesfattyliverandenhancesthermogenesisinbrownadiposetissueviainhibitingbmp4relatedsignalingpathwayinhighfatdietinducedobesemice AT bingweima glucagonlikepeptide1improvesfattyliverandenhancesthermogenesisinbrownadiposetissueviainhibitingbmp4relatedsignalingpathwayinhighfatdietinducedobesemice AT jiaqichen glucagonlikepeptide1improvesfattyliverandenhancesthermogenesisinbrownadiposetissueviainhibitingbmp4relatedsignalingpathwayinhighfatdietinducedobesemice AT huiyou glucagonlikepeptide1improvesfattyliverandenhancesthermogenesisinbrownadiposetissueviainhibitingbmp4relatedsignalingpathwayinhighfatdietinducedobesemice AT chunjunsheng glucagonlikepeptide1improvesfattyliverandenhancesthermogenesisinbrownadiposetissueviainhibitingbmp4relatedsignalingpathwayinhighfatdietinducedobesemice AT pengyang glucagonlikepeptide1improvesfattyliverandenhancesthermogenesisinbrownadiposetissueviainhibitingbmp4relatedsignalingpathwayinhighfatdietinducedobesemice AT shenqu glucagonlikepeptide1improvesfattyliverandenhancesthermogenesisinbrownadiposetissueviainhibitingbmp4relatedsignalingpathwayinhighfatdietinducedobesemice |