Yan Lin, Rust Bret M, Sundaram Sneha, Nielsen Forrest H
U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND, USA.
Nutr Metab Insights. 2024 Sep 28;17:11786388241280859. doi: 10.1177/11786388241280859. eCollection 2024.
Monocyte chemotactic protein-1 (MCP-1), a small inducible cytokine, is involved in obesity-related chronic disorders. Adipocytes produce MCP-1 that is elevated in obese humans and in rodent models of obesity. This study examined the hepatic metabolomic alterations caused by adipose-specific MCP-1 deficiency in a rodent model of obesity. Wide-type (WT) and adipose-specific knockdown mice ( ) were each assigned randomly to 2 groups and fed the standard AIN93G diet or a high-fat diet (HFD) for 12 weeks. Compared to the AIN93G diet, the HFD increased body weight, body fat mass, and plasma concentrations of insulin and leptin, regardless of genotype. There were no differences in these variables between WT and mice when they were fed the same diet. Eighty-seven of 172 identified metabolites met the criteria for metabolomic comparisons among the 4 groups. Thirty-nine metabolites differed significantly between the 2 dietary treatments and 15 differed when mice were compared to WT mice. The metabolites that significantly differed in both comparisons included those involved in amino acid, energy, lipid, nucleotide, and vitamin metabolism. Network analysis found that both HFD and adipose knockdown may considerably impact amino acid metabolism as evidenced by alteration in the aminoacyl-tRNA biosynthesis pathways, in addition to alteration in the phenylalanine, tyrosine, and tryptophan biosynthesis pathway in mice. However, decreased signals of amino acid metabolites in mice fed the HFD and increased signals of amino acid metabolites in mice indicate that HFD may have down-regulated and adipose knockdown may have up-regulated amino acid metabolism.
单核细胞趋化蛋白-1（MCP-1）是一种可诱导的小细胞因子，与肥胖相关的慢性疾病有关。脂肪细胞产生的MCP-1在肥胖人群和肥胖啮齿动物模型中水平升高。本研究在肥胖啮齿动物模型中检测了脂肪特异性MCP-1缺乏引起的肝脏代谢组学变化。将野生型（WT）和脂肪特异性敲低小鼠（ ）随机分为两组，分别给予标准AIN93G饮食或高脂饮食（HFD）12周。与AIN93G饮食相比，无论基因型如何，HFD均可增加体重、体脂量以及胰岛素和瘦素的血浆浓度。当给予相同饮食时，WT和 小鼠在这些变量上没有差异。在172种已鉴定的代谢物中，有87种符合4组之间代谢组学比较的标准。两种饮食处理之间有39种代谢物存在显著差异，与WT小鼠相比， 小鼠中有15种代谢物存在差异。在两项比较中均有显著差异的代谢物包括参与氨基酸、能量、脂质、核苷酸和维生素代谢的代谢物。网络分析发现，HFD和脂肪敲低均可显著影响氨基酸代谢，这不仅表现为氨酰-tRNA生物合成途径的改变，还表现为 小鼠中苯丙氨酸、酪氨酸和色氨酸生物合成途径的改变。然而，喂食HFD的小鼠中氨基酸代谢物信号降低，而 小鼠中氨基酸代谢物信号增加，这表明HFD可能下调了氨基酸代谢，而脂肪敲低可能上调了氨基酸代谢。
