Metabolic phenotyping of genetically modified mice: An NMR metabonomic approach☆

Monocyte chemoattractant protein-1 (MCP-1) plays a relevant role in macrophage migration but recentfindings suggest an additional role in lipid and glucose metabolism. We report the use of 1 H NMRspectroscopy as a useful complementary method to assess the metabolic function of this gene ina comparative strategy. This metabonomic analysis was rapid, simple, quantitative and reproducible, andrevealed a suggestive relationship between the expression of the MCP-1 gene and hepatic glucose andtaurine concentrations. This approach should be considered in genetically modified mice when a meta-bolic alteration is suspected, or in routine assessment of metabolic phenotype. 2009 Elsevier Masson SAS. All rights reserved. 1. IntroductionThe evaluation of the activity of candidate genes or proteinsthrough transcriptomics and proteomics is usually expensive andcomplex. With the rationale that small differences in metabolismmay result in pronounced changes in metabolite concentrations,we designed a metabonomic approach to assess the function ofselected genes in genetically modified mice using a comparativestrategy between knockout and derived double-knockout mice. Totest this approach we chose MCP-1. Although the main rolereported for MCP-1 is related to monocyte trafficking and otherimmunological functions [1,2], there is evidence to suggest that itparticipates in metabolism [3]. We have demonstrated that MCP-1is involved in the development of obesity and in impaired glucosemetabolism in LDLr-deficient mice (LDLr