Lin Yan, Bret M Rust, Sneha Sundaram, Forrest H Nielsen
{"title":"Metabolomic Alteration in Adipose Monocyte Chemotactic Protein-1 Deficient Mice Fed a High-Fat Diet.","authors":"Lin Yan, Bret M Rust, Sneha Sundaram, Forrest H Nielsen","doi":"10.1177/11786388241280859","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>Mcp-1</i> knockdown mice (<i>Mcp-1</i> <sup>-/-</sup>) 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 <i>Mcp-1</i> <sup>-/-</sup> 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 <i>Mcp-1</i> <sup>-/-</sup> 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 <i>Mcp-1</i> 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 <i>Mcp-1</i> <sup>-/-</sup> mice. However, decreased signals of amino acid metabolites in mice fed the HFD and increased signals of amino acid metabolites in <i>Mcp-1</i> <sup>-/-</sup> mice indicate that HFD may have down-regulated and adipose <i>Mcp-1</i> knockdown may have up-regulated amino acid metabolism.</p>","PeriodicalId":19396,"journal":{"name":"Nutrition and Metabolic Insights","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452861/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nutrition and Metabolic Insights","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/11786388241280859","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.