Alleviating effect of Lactobacillus fermentum E15 on hyperlipidemia and hepatic lipid metabolism in zebrafish fed by a high-fat diet through the production of short-chain fatty acids
IntroductionHyperlipidemia is regarded as one of the crucial factors leading to atherosclerosis and other cardiovascular diseases. Gut microbiota plays an important role in regulating host lipid metabolism. Nevertheless, the exact mechanisms behind this remain unclear.MethodsIn the present study, a...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2025.1522982/full |
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| author | Yishu Chen Kangdi Zheng Yang Leng Zhao Zhang Zhao Zhang Xiaoling Li Xiaoyan Li Huajun Ou Muhao Wen Feng Qiu Huajun Yu |
| author_facet | Yishu Chen Kangdi Zheng Yang Leng Zhao Zhang Zhao Zhang Xiaoling Li Xiaoyan Li Huajun Ou Muhao Wen Feng Qiu Huajun Yu |
| author_sort | Yishu Chen |
| collection | DOAJ |
| description | IntroductionHyperlipidemia is regarded as one of the crucial factors leading to atherosclerosis and other cardiovascular diseases. Gut microbiota plays an important role in regulating host lipid metabolism. Nevertheless, the exact mechanisms behind this remain unclear.MethodsIn the present study, a hyperlipidemic zebrafish model was established using a high-cholesterol diet (HCD) to evaluate the anti-hyperlipidemic effects of Lactobacillus fermentum E15 (L. fermentum E15).ResultsResults showed that L. fermentum E15 effectively reduced lipid accumulation in the blood vessels and liver of HCD-fed zebrafish larvae. Meanwhile, L. fermentum E15 improved abnormal lipid levels, and normalized liver enzyme activity. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis revealed that L. fermentum E15 downregulated the expression of sterol regulatory element-binding factor (SREBP-1), peroxisome proliferator-activated receptor-gamma (PPAR-γ), and fatty acid synthase (Fasn), while upregulated peroxisome proliferator-activated receptor-alpha (PPAR-α). Additionally, metabolomic analysis revealed that L. fermentum E15 produced a series of short-chain fatty acids (SCFAs), including acetic acid, propionic acid, butyric acid, and isovaleric acid. Notably, isovaleric acid contributed to the reduction of lipid droplet accumulation in the liver and blood vessels of HCD-fed zebrafish larvae. In contrast, blocking G-protein coupled receptor 43 (GPR43) with pertussis toxin (PTX) abolished the effects of L. fermentum E15 and isovaleric acid on reducing lipid accumulation in HCD-fed zebrafish larvae. RT-qPCR results further suggested that both L. fermentum E15 and isovaleric acid promoted the expression of GPR43 and leptin A, which was inhibited by PTX.ConclusionThese findings suggested that L. fermentum E15 alleviates HCD-induced hyperlipidemia by activating GPR43 through SCFAs. |
| format | Article |
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| institution | OA Journals |
| issn | 2296-861X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Nutrition |
| spelling | doaj-art-5b5d4cee9bcc47a49c4b2ca7e774a2d22025-08-20T02:18:20ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2025-03-011210.3389/fnut.2025.15229821522982Alleviating effect of Lactobacillus fermentum E15 on hyperlipidemia and hepatic lipid metabolism in zebrafish fed by a high-fat diet through the production of short-chain fatty acidsYishu Chen0Kangdi Zheng1Yang Leng2Zhao Zhang3Zhao Zhang4Xiaoling Li5Xiaoyan Li6Huajun Ou7Muhao Wen8Feng Qiu9Huajun Yu10Laboratory Animal Center, Guangdong Medical University, Zhanjiang, ChinaGuangdong Longseek Testing Co., Ltd., Guangzhou, ChinaLaboratory Animal Center, Guangdong Medical University, Zhanjiang, ChinaLaboratory Animal Center, Guangdong Medical University, Zhanjiang, ChinaGuangdong Longseek Testing Co., Ltd., Guangzhou, ChinaLaboratory Animal Center, Guangdong Medical University, Zhanjiang, ChinaLaboratory Animal Center, Guangdong Medical University, Zhanjiang, ChinaLaboratory Animal Center, Guangdong Medical University, Zhanjiang, ChinaDepartment of Laboratory Medicine, the Seventh Affiliated Hospital of Southern Medical University, Foshan, ChinaDepartment of Laboratory Medicine, the Seventh Affiliated Hospital of Southern Medical University, Foshan, ChinaLaboratory Animal Center, Guangdong Medical University, Zhanjiang, ChinaIntroductionHyperlipidemia is regarded as one of the crucial factors leading to atherosclerosis and other cardiovascular diseases. Gut microbiota plays an important role in regulating host lipid metabolism. Nevertheless, the exact mechanisms behind this remain unclear.MethodsIn the present study, a hyperlipidemic zebrafish model was established using a high-cholesterol diet (HCD) to evaluate the anti-hyperlipidemic effects of Lactobacillus fermentum E15 (L. fermentum E15).ResultsResults showed that L. fermentum E15 effectively reduced lipid accumulation in the blood vessels and liver of HCD-fed zebrafish larvae. Meanwhile, L. fermentum E15 improved abnormal lipid levels, and normalized liver enzyme activity. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis revealed that L. fermentum E15 downregulated the expression of sterol regulatory element-binding factor (SREBP-1), peroxisome proliferator-activated receptor-gamma (PPAR-γ), and fatty acid synthase (Fasn), while upregulated peroxisome proliferator-activated receptor-alpha (PPAR-α). Additionally, metabolomic analysis revealed that L. fermentum E15 produced a series of short-chain fatty acids (SCFAs), including acetic acid, propionic acid, butyric acid, and isovaleric acid. Notably, isovaleric acid contributed to the reduction of lipid droplet accumulation in the liver and blood vessels of HCD-fed zebrafish larvae. In contrast, blocking G-protein coupled receptor 43 (GPR43) with pertussis toxin (PTX) abolished the effects of L. fermentum E15 and isovaleric acid on reducing lipid accumulation in HCD-fed zebrafish larvae. RT-qPCR results further suggested that both L. fermentum E15 and isovaleric acid promoted the expression of GPR43 and leptin A, which was inhibited by PTX.ConclusionThese findings suggested that L. fermentum E15 alleviates HCD-induced hyperlipidemia by activating GPR43 through SCFAs.https://www.frontiersin.org/articles/10.3389/fnut.2025.1522982/fullLactobacillus fermentum E15short-chain fatty acidshyperlipidemiahigh-cholesterol dietzebrafish |
| spellingShingle | Yishu Chen Kangdi Zheng Yang Leng Zhao Zhang Zhao Zhang Xiaoling Li Xiaoyan Li Huajun Ou Muhao Wen Feng Qiu Huajun Yu Alleviating effect of Lactobacillus fermentum E15 on hyperlipidemia and hepatic lipid metabolism in zebrafish fed by a high-fat diet through the production of short-chain fatty acids Frontiers in Nutrition Lactobacillus fermentum E15 short-chain fatty acids hyperlipidemia high-cholesterol diet zebrafish |
| title | Alleviating effect of Lactobacillus fermentum E15 on hyperlipidemia and hepatic lipid metabolism in zebrafish fed by a high-fat diet through the production of short-chain fatty acids |
| title_full | Alleviating effect of Lactobacillus fermentum E15 on hyperlipidemia and hepatic lipid metabolism in zebrafish fed by a high-fat diet through the production of short-chain fatty acids |
| title_fullStr | Alleviating effect of Lactobacillus fermentum E15 on hyperlipidemia and hepatic lipid metabolism in zebrafish fed by a high-fat diet through the production of short-chain fatty acids |
| title_full_unstemmed | Alleviating effect of Lactobacillus fermentum E15 on hyperlipidemia and hepatic lipid metabolism in zebrafish fed by a high-fat diet through the production of short-chain fatty acids |
| title_short | Alleviating effect of Lactobacillus fermentum E15 on hyperlipidemia and hepatic lipid metabolism in zebrafish fed by a high-fat diet through the production of short-chain fatty acids |
| title_sort | alleviating effect of lactobacillus fermentum e15 on hyperlipidemia and hepatic lipid metabolism in zebrafish fed by a high fat diet through the production of short chain fatty acids |
| topic | Lactobacillus fermentum E15 short-chain fatty acids hyperlipidemia high-cholesterol diet zebrafish |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2025.1522982/full |
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