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.

IF 4 2区农林科学 Q2 NUTRITION & DIETETICS Frontiers in Nutrition Pub Date : 2025-03-03 eCollection Date: 2025-01-01 DOI:10.3389/fnut.2025.1522982

Yishu Chen, Kangdi Zheng, Yang Leng, Zhao Zhang, Xiaoling Li, Xiaoyan Li, Huajun Ou, Muhao Wen, Feng Qiu, Huajun Yu

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Abstract

Introduction: Hyperlipidemia 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.

Methods: In 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).

Results: Results 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.

Conclusion: These findings suggested that L. fermentum E15 alleviates HCD-induced hyperlipidemia by activating GPR43 through SCFAs.

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来源期刊

Frontiers in Nutrition Agricultural and Biological Sciences-Food Science

CiteScore

5.20

自引率

8.00%

发文量

2891

审稿时长

12 weeks

期刊介绍： No subject pertains more to human life than nutrition. The aim of Frontiers in Nutrition is to integrate major scientific disciplines in this vast field in order to address the most relevant and pertinent questions and developments. Our ambition is to create an integrated podium based on original research, clinical trials, and contemporary reviews to build a reputable knowledge forum in the domains of human health, dietary behaviors, agronomy & 21st century food science. Through the recognized open-access Frontiers platform we welcome manuscripts to our dedicated sections relating to different areas in the field of nutrition with a focus on human health. Specialty sections in Frontiers in Nutrition include, for example, Clinical Nutrition, Nutrition & Sustainable Diets, Nutrition and Food Science Technology, Nutrition Methodology, Sport & Exercise Nutrition, Food Chemistry, and Nutritional Immunology. Based on the publication of rigorous scientific research, we thrive to achieve a visible impact on the global nutrition agenda addressing the grand challenges of our time, including obesity, malnutrition, hunger, food waste, sustainability and consumer health.