A combined 1H-NMR spectroscopy- and mass spectrometry-based metabolomic study of the PPAR-alpha null mutant mouse defines profound systemic changes in metabolism linked to the metabolic syndrome - PubMed (original) (raw)

A combined 1H-NMR spectroscopy- and mass spectrometry-based metabolomic study of the PPAR-alpha null mutant mouse defines profound systemic changes in metabolism linked to the metabolic syndrome

Helen J Atherton et al. Physiol Genomics. 2006.

Abstract

The mobilization of triacylglycerides from storage in adipocytes to the liver is a vital response to the fasting state in mammalian metabolism. This is accompanied by a rapid translational activation of genes encoding mitochondrial, microsomal, and peroxisomal beta-oxidation in the liver, in part under the regulation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha). A failure to express PPAR-alpha results in profound metabolic perturbations in muscle tissue as well as the liver. These changes represent a number of deficits that accompany diabetes, dyslipidemia, and the metabolic syndrome. In this study, the metabolic role of PPAR-alpha has been investigated in heart, skeletal muscle, liver, and adipose tissue of PPAR-alpha null mice at 1 mo of age using metabolomics. To maximize the coverage of the metabolome in these tissues, (1)H-NMR spectroscopy, magic angle spinning (1)H-NMR spectroscopy, gas chromatography-mass spectrometry, and liquid chromatography-mass spectrometry were used to examine metabolites in aqueous tissue extracts and intact tissue. The data were analyzed by the multivariate approaches of principal components analysis and partial least squares. Across all tissues, there was a profound decrease in glucose and a number of amino acids, including glutamine and alanine, and an increase in lactate, demonstrating that a failure to express PPAR-alpha results in perturbations in glycolysis, the citric acid cycle, and gluconeogenesis. Furthermore, despite PPAR-alpha being weakly expressed in adipose tissue, a profound metabolic perturbation was detected in this tissue.

PubMed Disclaimer

Cited by

Role of PPARα in Hepatic Carbohydrate Metabolism.
Peeters A, Baes M. Peeters A, et al. PPAR Res. 2010;2010:572405. doi: 10.1155/2010/572405. Epub 2010 Sep 30. PPAR Res. 2010. PMID: 20936117 Free PMC article.
Global urinary metabolic profiling procedures using gas chromatography-mass spectrometry.
Chan EC, Pasikanti KK, Nicholson JK. Chan EC, et al. Nat Protoc. 2011 Sep 8;6(10):1483-99. doi: 10.1038/nprot.2011.375. Nat Protoc. 2011. PMID: 21959233
Applications of metabolomics and proteomics to the mdx mouse model of Duchenne muscular dystrophy: lessons from downstream of the transcriptome.
Griffin JL, Des Rosiers C. Griffin JL, et al. Genome Med. 2009 Mar 25;1(3):32. doi: 10.1186/gm32. Genome Med. 2009. PMID: 19341503 Free PMC article.
PPAR-pan activation induces hepatic oxidative stress and lipidomic remodelling.
Ament Z, West JA, Stanley E, Ashmore T, Roberts LD, Wright J, Nicholls AW, Griffin JL. Ament Z, et al. Free Radic Biol Med. 2016 Jun;95:357-68. doi: 10.1016/j.freeradbiomed.2015.11.033. Epub 2015 Nov 30. Free Radic Biol Med. 2016. PMID: 26654758 Free PMC article.
Progress in Metabolomics Standardisation and its Significance in Future Clinical Laboratory Medicine.
Dias DA, Koal T. Dias DA, et al. EJIFCC. 2016 Dec 1;27(4):331-343. eCollection 2016 Dec. EJIFCC. 2016. PMID: 28149265 Free PMC article.

A combined 1H-NMR spectroscopy- and mass spectrometry-based metabolomic study of the PPAR-alpha null mutant mouse defines profound systemic changes in metabolism linked to the metabolic syndrome - PubMed (original) (raw)