以高脂肪饮食喂养的脂肪单核细胞趋化蛋白-1 缺乏症小鼠的代谢组变化

IF 2.3 Q3 NUTRITION & DIETETICS Nutrition and Metabolic Insights Pub Date : 2024-09-28 eCollection Date: 2024-01-01 DOI:10.1177/11786388241280859
Lin Yan, Bret M Rust, Sneha Sundaram, Forrest H Nielsen
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引用次数: 0

摘要

单核细胞趋化蛋白-1(MCP-1)是一种小型诱导性细胞因子,与肥胖相关的慢性疾病有关。脂肪细胞产生的 MCP-1 在肥胖的人类和肥胖的啮齿动物模型中都会升高。本研究在肥胖啮齿动物模型中考察了脂肪特异性 MCP-1 缺乏引起的肝脏代谢组学改变。将宽型(WT)和脂肪特异性MCP-1基因敲除小鼠(MCP-1 -/-)随机分为两组,分别喂食标准AIN93G饮食或高脂饮食(HFD)12周。与 AIN93G 饮食相比,无论基因型如何,高脂饮食都会增加体重、体脂质量以及胰岛素和瘦素的血浆浓度。WT小鼠和Mcp-1 -/-小鼠在喂食相同食物时,这些变量没有差异。在 172 个已确定的代谢物中,有 87 个符合在 4 个组间进行代谢组比较的标准。当 Mcp-1 -/- 小鼠与 WT 小鼠进行比较时,39 种代谢物在两种饮食处理之间存在显著差异,15 种代谢物存在差异。在这两种比较中存在显著差异的代谢物包括氨基酸、能量、脂质、核苷酸和维生素代谢物。网络分析发现,HFD和脂肪Mcp-1基因敲除都可能对氨基酸代谢产生重大影响,这体现在Mcp-1 -/-小鼠的氨基酰-tRNA生物合成途径发生了改变,此外,苯丙氨酸、酪氨酸和色氨酸生物合成途径也发生了改变。然而,喂食高饱和脂肪酸的小鼠体内氨基酸代谢物信号降低,而Mcp-1 -/-小鼠体内氨基酸代谢物信号升高,这表明高饱和脂肪酸可能下调了氨基酸代谢,而脂肪Mcp-1基因敲除可能上调了氨基酸代谢。
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Metabolomic Alteration in Adipose Monocyte Chemotactic Protein-1 Deficient Mice Fed a High-Fat Diet.

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 Mcp-1 knockdown mice (Mcp-1 -/-) 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 Mcp-1 -/- 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 Mcp-1 -/- 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 Mcp-1 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 Mcp-1 -/- mice. However, decreased signals of amino acid metabolites in mice fed the HFD and increased signals of amino acid metabolites in Mcp-1 -/- mice indicate that HFD may have down-regulated and adipose Mcp-1 knockdown may have up-regulated amino acid metabolism.

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来源期刊
Nutrition and Metabolic Insights
Nutrition and Metabolic Insights NUTRITION & DIETETICS-
CiteScore
3.30
自引率
0.00%
发文量
27
审稿时长
8 weeks
期刊介绍: Nutrition and Metabolic Insights is a peer-reviewed, open-access online journal focusing on all aspects of nutrition and metabolism. This encompasses nutrition, including the biochemistry of metabolism, exercise and associated physical processes and also includes clinical articles that relate to metabolism, such as obesity, lipidemias and diabetes. It includes research at the molecular, cellular and organismal levels. This journal welcomes new manuscripts for peer review on the following topics: Nutrition, including the biochemistry of metabolism, Exercise and associated physical processes, Clinical articles that relate to metabolism, such as obesity, lipidemias and diabetes, Research at the molecular, cellular and organismal levels, Other areas of interest include gene-nutrient interactions, the effects of hormones, models of metabolic function, macronutrient interactions, outcomes of changes in diet, and pathophysiology.
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