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Metabolomics of the interaction between PPAR-alpha and age in the PPAR-alpha- mouse.

Atherton HJ, Gulston MK, Bailey NJ, Cheng KK, Zhang W, Clarke K, Griffin JL - Mol. Syst. Biol. (2009)

Bottom Line: Expression of the receptor is high in the liver, heart and skeletal muscle, but decreases with age.Hepatic glycogen and glucose also decreased with age for both genotypes.Furthermore, the combined metabolomic and multivariate statistics approach provides a robust method for examining the interaction between age and genotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry & Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK.

ABSTRACT
Regulation between the fed and fasted states in mammals is partially controlled by peroxisome proliferator-activated receptor-alpha (PPAR-alpha). Expression of the receptor is high in the liver, heart and skeletal muscle, but decreases with age. A combined (1)H nuclear magnetic resonance (NMR) spectroscopy and gas chromatography-mass spectrometry metabolomic approach has been used to examine metabolism in the liver, heart, skeletal muscle and adipose tissue in PPAR-alpha- mice and wild-type controls during ageing between 3 and 13 months. For the PPAR-alpha- mouse, multivariate statistics highlighted hepatic steatosis, reductions in the concentrations of glucose and glycogen in both the liver and muscle tissue, and profound changes in lipid metabolism in each tissue, reflecting known expression targets of the PPAR-alpha receptor. Hepatic glycogen and glucose also decreased with age for both genotypes. These findings indicate the development of age-related hepatic steatosis in the PPAR-alpha- mouse, with the normal metabolic changes associated with ageing exacerbating changes associated with genotype. Furthermore, the combined metabolomic and multivariate statistics approach provides a robust method for examining the interaction between age and genotype.

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Related in: MedlinePlus

A summary figure of the key changes between wild-type and PPAR-α- mice and associated with ageing in both mouse genotypes.
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f4: A summary figure of the key changes between wild-type and PPAR-α- mice and associated with ageing in both mouse genotypes.

Mentions: GC-MS analysis of the heart also showed a reduction in β-hydroxybutyrate, a ketone body used to supply energy to the heart under conditions of low glucose intake. This reduction was evident at 5 and 9 months (data not shown). A complete list of the most significant changes is available as part of the online Supplementary Tables 1–9 and summarised in Figure 4.


Metabolomics of the interaction between PPAR-alpha and age in the PPAR-alpha- mouse.

Atherton HJ, Gulston MK, Bailey NJ, Cheng KK, Zhang W, Clarke K, Griffin JL - Mol. Syst. Biol. (2009)

A summary figure of the key changes between wild-type and PPAR-α- mice and associated with ageing in both mouse genotypes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2683722&req=5

f4: A summary figure of the key changes between wild-type and PPAR-α- mice and associated with ageing in both mouse genotypes.
Mentions: GC-MS analysis of the heart also showed a reduction in β-hydroxybutyrate, a ketone body used to supply energy to the heart under conditions of low glucose intake. This reduction was evident at 5 and 9 months (data not shown). A complete list of the most significant changes is available as part of the online Supplementary Tables 1–9 and summarised in Figure 4.

Bottom Line: Expression of the receptor is high in the liver, heart and skeletal muscle, but decreases with age.Hepatic glycogen and glucose also decreased with age for both genotypes.Furthermore, the combined metabolomic and multivariate statistics approach provides a robust method for examining the interaction between age and genotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry & Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK.

ABSTRACT
Regulation between the fed and fasted states in mammals is partially controlled by peroxisome proliferator-activated receptor-alpha (PPAR-alpha). Expression of the receptor is high in the liver, heart and skeletal muscle, but decreases with age. A combined (1)H nuclear magnetic resonance (NMR) spectroscopy and gas chromatography-mass spectrometry metabolomic approach has been used to examine metabolism in the liver, heart, skeletal muscle and adipose tissue in PPAR-alpha- mice and wild-type controls during ageing between 3 and 13 months. For the PPAR-alpha- mouse, multivariate statistics highlighted hepatic steatosis, reductions in the concentrations of glucose and glycogen in both the liver and muscle tissue, and profound changes in lipid metabolism in each tissue, reflecting known expression targets of the PPAR-alpha receptor. Hepatic glycogen and glucose also decreased with age for both genotypes. These findings indicate the development of age-related hepatic steatosis in the PPAR-alpha- mouse, with the normal metabolic changes associated with ageing exacerbating changes associated with genotype. Furthermore, the combined metabolomic and multivariate statistics approach provides a robust method for examining the interaction between age and genotype.

Show MeSH
Related in: MedlinePlus