Effects of Adipose Tissue-Specific Knockout of Delta-like Non-Canonical Notch Ligand 1 on Lipid Metabolism in Mice

IF 4.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY International Journal of Molecular Sciences Pub Date : 2023-12-21 DOI:10.3390/ijms25010132
Xin Lu, Xibi Fang, Jiaqi Mi, Yue Liu, Ruimin Liu, Guanghui Li, Yue Li, Runjun Yang
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Abstract

Delta-like non-canonical Notch ligand 1 (DLK1), which inhibits the differentiation of precursor adipocytes, is a recognized marker gene for precursor adipocytes. Lipids play a crucial role in energy storage and metabolism as a vital determinant of beef quality. In this study, we investigated the mechanism of the DLK1 gene in lipid metabolism by constructing adipose tissue-specific knockout mice. We examined some phenotypic traits, including body weight, liver coefficient, fat index, the content of triglyceride (TG) and cholesterol (CHOL) in abdominal white adipose tissue (WAT) and blood. Subsequently, the fatty acid content and genes related to lipid metabolism expression were detected in DLK1−/− and wild-type mice via GC-MS/MS analysis and quantitative real-time PCR (qRT-PCR), respectively. The results illustrated that DLK1−/− mice exhibited significant abdominal fat deposition compared to wild-type mice. HE staining and immunohistochemistry (IHC) results showed that the white adipocytes of DLK1−/− mice were larger, and the protein expression level of DLK1−/− was significantly lower. Regarding the blood biochemical parameters of female mice, DLK1−/− mice had a strikingly higher triglyceride content (p < 0.001). The fatty acid content in DLK1−/− mice was generally reduced. There was a significant reduction in the expression levels of the majority of genes that play a crucial role in lipid metabolism. This study reveals the molecular regulatory mechanism of fat metabolism in mice and provides a molecular basis and reference for the future application of the DLK1 gene in the breeding of beef cattle with an excellent meat quality traits. It also provides a molecular basis for unravelling the complex and subtle relationship between adipose tissue and health.
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脂肪组织特异性敲除δ样非典型缺口配体 1 对小鼠脂质代谢的影响
Delta样非典型Notch配体1(DLK1)可抑制前体脂肪细胞的分化,是公认的前体脂肪细胞标记基因。脂质在能量储存和新陈代谢中起着至关重要的作用,是牛肉品质的重要决定因素。本研究通过构建脂肪组织特异性基因敲除小鼠,研究了 DLK1 基因在脂质代谢中的作用机制。我们检测了一些表型性状,包括体重、肝脏系数、脂肪指数、腹部白色脂肪组织(WAT)和血液中甘油三酯(TG)和胆固醇(CHOL)的含量。随后,通过GC-MS/MS分析和实时定量PCR(qRT-PCR)分别检测了DLK1-/-和野生型小鼠的脂肪酸含量和脂质代谢相关基因的表达。结果表明,与野生型小鼠相比,DLK1-/-小鼠腹部脂肪沉积明显。HE染色和免疫组化(IHC)结果显示,DLK1-/-小鼠的白色脂肪细胞体积更大,DLK1-/-的蛋白表达水平明显降低。在雌性小鼠的血液生化指标方面,DLK1-/-小鼠的甘油三酯含量明显升高(p < 0.001)。DLK1-/-小鼠的脂肪酸含量普遍降低。在脂质代谢中起关键作用的大多数基因的表达水平明显降低。这项研究揭示了小鼠脂肪代谢的分子调控机制,为今后应用 DLK1 基因培育肉质优良的肉牛提供了分子基础和参考。它还为揭示脂肪组织与健康之间复杂而微妙的关系提供了分子基础。
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来源期刊
International Journal of Molecular Sciences
International Journal of Molecular Sciences Chemistry-Organic Chemistry
CiteScore
8.10
自引率
10.70%
发文量
13472
审稿时长
17.49 days
期刊介绍: The International Journal of Molecular Sciences (ISSN 1422-0067) provides an advanced forum for chemistry, molecular physics (chemical physics and physical chemistry) and molecular biology. It publishes research articles, reviews, communications and short notes. Our aim is to encourage scientists to publish their theoretical and experimental results in as much detail as possible. Therefore, there is no restriction on the length of the papers or the number of electronics supplementary files. For articles with computational results, the full experimental details must be provided so that the results can be reproduced. Electronic files regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material (including animated pictures, videos, interactive Excel sheets, software executables and others).
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