Department of Animal Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310030, PR China.
Jinan Laiwu Pig Industry Technology Research Institute Co., Ltd, Jinan, 271100, China.
Microbiome. 2024 Oct 30;12(1):223. doi: 10.1186/s40168-024-01944-4.
Obesity in humans can lead to chronic diseases such as diabetes and cardiovascular disease. Similarly, subcutaneous fat (SCF) in pigs affects feed utilization, and excessive SCF can reduce the feed efficiency of pigs. Therefore, identifying factors that suppress fat deposition is particularly important. Numerous studies have implicated the gut microbiome in pigs' fat deposition, but research into its suppression remains scarce. The Lulai black pig (LL) is a hybrid breed derived from the Laiwu pig (LW) and the Yorkshire pig, with lower levels of SCF compared to the LW. In this study, we focused on these breeds to identify microbiota that regulate fat deposition. The key questions were: Which microbial populations reduce fat in LL pigs compared to LW pigs, and what is the underlying regulatory mechanism?
In this study, we identified four different microbial strains, Eubacterium siraeum, Treponema bryantii, Clostridium sp. CAG:413, and Jeotgalibaca dankookensis, prevalent in both LW and LL pigs. Blood metabolome analysis revealed 49 differential metabolites, including tanshinone IIA and royal jelly acid, known for their anti-adipogenic properties. E. siraeum was strongly correlated with these metabolites, and its genes and metabolites were enriched in pathways linked to fatty acid degradation, glycerophospholipid, and glycerolipid metabolism. In vivo mouse experiments confirmed that E. siraeum metabolites curb weight gain, reduce SCF adipocyte size, increase the number of brown adipocytes, and regulate leptin, IL-6, and insulin secretion. Finally, we found that one important pathway through which E. siraeum inhibits fat deposition is by suppressing the phosphorylation of key proteins in the PI3K/AKT signaling pathway through the reduction of tyrosine.
We compared LW and LL pigs using fecal metagenomics, metabolomics, and blood metabolomics, identifying E. siraeum as a strain linked to fat deposition. Oral administration experiments in mice demonstrated that E. siraeum effectively inhibits fat accumulation, primarily through the suppression of the PI3K/AKT signaling pathway, a critical regulator of lipid metabolism. These findings provide a valuable theoretical basis for improving pork quality and offer insights relevant to the study of human obesity and related chronic metabolic diseases. Video Abstract.
人体肥胖会导致糖尿病和心血管疾病等慢性病。同样，猪的皮下脂肪（SCF）会影响饲料利用率，过多的 SCF 会降低猪的饲料效率。因此，确定抑制脂肪沉积的因素尤为重要。大量研究表明肠道微生物群与猪的脂肪沉积有关，但对其抑制作用的研究仍然很少。莱芜黑猪（LL）是由莱芜猪（LW）和约克夏猪杂交而成的品种，与 LW 相比，其 SCF 水平较低。在这项研究中，我们专注于这些品种，以确定调节脂肪沉积的微生物群。关键问题是：与 LW 猪相比，哪些微生物种群减少了 LL 猪的脂肪，其潜在的调节机制是什么？
在这项研究中，我们鉴定了四种不同的微生物菌株，即丁酸梭菌、栖瘤胃普雷沃氏菌、短双歧杆菌和詹氏甲烷球菌，它们在 LW 和 LL 猪中都很普遍。血液代谢组学分析显示了 49 种差异代谢物，包括丹参酮 IIA 和蜂王浆酸，它们以抗脂肪生成特性而闻名。E. siraeum 与这些代谢物强烈相关，其基因和代谢物在与脂肪酸降解、甘油磷脂和甘油脂代谢相关的途径中富集。体内小鼠实验证实，E. siraeum 代谢物可抑制体重增加，减少 SCF 脂肪细胞大小，增加棕色脂肪细胞数量，并调节瘦素、IL-6 和胰岛素分泌。最后，我们发现 E. siraeum 通过抑制 PI3K/AKT 信号通路关键蛋白的磷酸化来抑制脂肪沉积的一个重要途径是通过减少酪氨酸。
我们使用粪便宏基因组学、代谢组学和血液代谢组学比较了 LW 和 LL 猪，发现 E. siraeum 是一种与脂肪沉积相关的菌株。在小鼠口服给药实验中，我们证明 E. siraeum 能有效抑制脂肪积累，主要是通过抑制 PI3K/AKT 信号通路，该通路是脂质代谢的关键调节剂。这些发现为改善猪肉质量提供了有价值的理论基础，并为研究人类肥胖和相关慢性代谢性疾病提供了启示。
