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UCP1 敲入猪通过脂肪-肝脏-肠道轴重塑粪便微生物群,并有助于减少脂肪沉积。

Fecal Microbiota Was Reshaped in UCP1 Knock-In Pigs via the Adipose-Liver-Gut Axis and Contributed to Less Fat Deposition.

机构信息

State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, People's Republic of China.

College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, People's Republic of China.

出版信息

Microbiol Spectr. 2023 Feb 14;11(1):e0354022. doi: 10.1128/spectrum.03540-22. Epub 2023 Jan 23.

DOI:10.1128/spectrum.03540-22
PMID:36688695
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9927592/
Abstract

The relationship between the host gut microbiota and obesity has been well documented in humans and mice; however, few studies reported the association between the gut microbiota and fat deposition in pigs. In a previous study, we generated uncoupling protein 1 (UCP1) knock-in pigs (UCP1 pigs), which exhibited a lower fat deposition phenotype. Whether the gut microbiota was reshaped in these pigs and whether the reshaped gut microbiota contributes to the lower fat content remain unknown. Here, we revealed that the fecal microbiota composition and metabolites were significantly altered under both chow diet (CD) and high-fat/high-cholesterol (HFHC) diet conditions in UCP1 pigs compared to those in wild-type (WT) pigs. The abundance of and and the level of metabolite hyodeoxycholic acid (HDCA) from feces were observed to be significantly increased in UCP1 pigs. An association analysis revealed that and were significantly negatively related to backfat thickness. In addition, after fecal microbiota transplantation (FMT), the mice that were orally gavaged with feces from UCP1 pigs exhibited less fat deposition under both CD and high-fat diet (HFD) conditions, suggesting that the fecal microbes of UCP1 pigs participate in regulating host lipid metabolism. Consistently, HDCA-treated mice also exhibited reduced fat content. Mechanistically, we found that UCP1 expression in white adipose tissue alters the gut microbiota via the adipose-liver-gut axis in pigs. Our study provides new data concerning the cross talk between host genetic variations and the gut microbiota and paves the way for the potential application of microbes or their metabolites in the regulation of fat deposition in pigs. This article investigated the effect of the ectopic expression of UCP1 on the regulation of fecal microbiota composition and metabolites and which alters the fat deposition phenotype. Bacteria, including and , and the metabolite HDCA were found to be significantly increased in feces of UCP1 pigs and had a negative relationship with backfat thickness. Mice with fecal microbiota transplantation phenocopied the UCP1 pigs under both CD and HFD conditions, suggesting that the fecal microbes of UCP1 pigs participate in regulating host lipid metabolism. Our study provides new data regarding the cross talk between host genetic variations and the gut microbiota and paves the way for the potential application of microbes or their metabolic production in the regulation of fat deposition in pigs.

摘要

宿主肠道微生物群与肥胖的关系在人类和小鼠中已有充分的文献记载;然而,很少有研究报道肠道微生物群与猪的脂肪沉积之间的关系。在之前的一项研究中,我们生成了解偶联蛋白 1(UCP1)敲入猪(UCP1 猪),它们表现出较低的脂肪沉积表型。这些猪的肠道微生物群是否发生了重塑,以及重塑的肠道微生物群是否有助于降低脂肪含量仍不清楚。在这里,我们揭示了与野生型(WT)猪相比,UCP1 猪的粪便微生物群组成和代谢物在标准饮食(CD)和高脂肪/高胆固醇(HFHC)饮食条件下均发生了显著改变。在 UCP1 猪中观察到粪便中 和 的丰度和代谢产物去氧胆酸(HDCA)的水平显著增加。关联分析显示, 和 与背膘厚度呈显著负相关。此外,在粪便微生物群移植(FMT)后,经口灌胃 UCP1 猪粪便的小鼠在 CD 和高脂肪饮食(HFD)条件下表现出较少的脂肪沉积,表明 UCP1 猪的粪便微生物参与调节宿主脂质代谢。一致地,用 HDCA 处理的小鼠也表现出脂肪含量减少。在机制上,我们发现 UCP1 在白色脂肪组织中的表达通过猪的脂肪-肝-肠轴改变肠道微生物群。我们的研究提供了宿主遗传变异与肠道微生物群之间相互作用的新数据,并为微生物或其代谢产物在调节猪脂肪沉积中的潜在应用铺平了道路。本文研究了 UCP1 的异位表达对调节粪便微生物群组成和代谢物的影响,以及这种调节如何改变脂肪沉积表型。在 UCP1 猪的粪便中发现了细菌,包括 和 ,以及代谢物 HDCA,它们的丰度显著增加,与背膘厚度呈负相关。在 CD 和 HFD 条件下,进行粪便微生物群移植的小鼠表现出与 UCP1 猪相似的表型,这表明 UCP1 猪的粪便微生物参与调节宿主脂质代谢。我们的研究提供了宿主遗传变异与肠道微生物群之间相互作用的新数据,并为微生物或其代谢产物在调节猪脂肪沉积中的潜在应用铺平了道路。

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Multi-Omic Analysis in a Metabolic Syndrome Porcine Model Implicates Arachidonic Acid Metabolism Disorder as a Risk Factor for Atherosclerosis.
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