Metabolomics of the interaction between PPAR‐α and age in the PPAR‐α‐null mouse

Atherton, Helen; Gulston, Melanie K.; Bailey, Nigel J.; Cheng, Kian Kai; Zhang, Wen; Clarke, Kieran; Griffin, Julian L.

doi:10.1038/msb.2009.18

Cited by 72 publications

(54 citation statements)

References 42 publications

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“…In a previous study, it was reported that plasma TG, glucose, insulin, and leptin levels are increased and liver TG level is increased with decreasing fatty acid oxidation in the liver in rats with aging (35). It is also reported that PPAR-␣-null mice show increased fatty acid accumulation and decreased cholesterol synthesis, glucose storage and gluconeogenesis in the liver with aging (36). In addition, with a diabetogenic diet, it is reported that plasma insulin level is increased with aging (37).…”

Section: Discussionmentioning

confidence: 96%

Increased Lipid Accumulation in Liver and White Adipose Tissue in Aging in the SAMP10 Mouse

Honma

Yanaka

Tsuduki

et al. 2011

J Nutr Sci Vitaminol

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SummaryThe population of elderly persons has increased worldwide. However, few studies have examined age-dependent changes in lipid and carbohydrate metabolism related to age-related diseases. The number of cases of metabolic syndrome is increasing worldwide and prevention of lifestyle diseases may lead to prolongation of lifespan. In this study, we examined age-dependent changes in lipid and carbohydrate metabolism in the senescenceaccelerated (SAM) P10 mouse. Tissue weights and biochemical parameters in plasma and liver were examined in SAMP10 mice aged 3, 6, 9 and 12 mo. White adipose tissue weight and the levels of liver triacylglycerol, plasma free fatty acids, and plasma insulin all showed increases with aging of the mice. To examine this mechanism in detail, aging-related changes in mRNA expression of genes related to lipid and carbohydrate metabolism were examined by DNA microarray analysis. The mRNA level for Hsd11b1 (hydroxysteroid 11-beta dehydrogenase 1), which increases insulin secretion and resistance, was elevated with aging in the liver of SAMP10 mice. These results show that lipid accumulation in liver and white adipose tissue is promoted by aging in SAMP10 mice through an increase in plasma insulin levels. Key Words aging, DNA microarray, Hsd11b1, hyperinsulinemia, SAMP10The population of elderly persons has increased worldwide ( 1 , 2 ) and this trend is expected to continue, with a concurrent increase in age-related diseases ( 2 ). Studies of aging are important for prevention of these diseases, maintenance of personal quality of life (QOL), and societal health. Many studies on age-related diseases have been performed, with a particular focus on encephalopathy ( 3-5 ). However, few studies have examined age-dependent changes in lipid and carbohydrate metabolism related to lifestyle diseases. The number of cases of metabolic syndrome is increasing worldwide ( 6 ) and prevention of lifestyle diseases may lead to prolongation of lifespan. Therefore, an understanding of the dependence of lifestyle diseases on aging is particularly important.In this study, we investigated age-dependent changes of lipid and carbohydrate metabolism in the senescenceaccelerated (SAM) P10 mouse. This mouse was developed in 1981 by a research team at Kyoto University ( 7 ). At present, there are nine senescence-prone inbred strains, which are referred to as SAMP1,2,3,6,7,8,9, 10 and 11 ( 8 ). The SAMP10 mouse exhibits encephalatrophy along with aging, which reflects learning and memory disorder ( 9 ). In this study, tissue weights and biochemical parameters for lipid and carbohydrate metabolism in plasma and liver were examined in SAMP10 mice aged 3, 6, 9, and 12 mo. To examine the mechanisms underlying age-dependent changes in lipid and carbohydrate metabolism, changes with age of mRNA levels for genes related to lipid and carbohydrate metabolism were examined by DNA microarray analysis. MATERIALS AND METHODS Animals and diets.All procedures were performed in accordance with the Animal Experiment Guidelines of Tohoku...

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Section: Discussionmentioning

confidence: 96%

Increased Lipid Accumulation in Liver and White Adipose Tissue in Aging in the SAMP10 Mouse

Honma

Yanaka

Tsuduki

et al. 2011

J Nutr Sci Vitaminol

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“…26 The following metabolites were assessed: glutamate, citrate, malate, and creatine. Data were expressed as relative to the control peak of TSP.…”

Section: Nmr Metabolomic Analysismentioning

confidence: 99%

Impaired In Vivo Mitochondrial Krebs Cycle Activity After Myocardial Infarction Assessed Using Hyperpolarized Magnetic Resonance Spectroscopy

Dodd

Atherton

Carr

et al. 2014

Circ: Cardiovascular Imaging

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M yocardial infarction (MI) is the leading cause of heart failure in the developed world and results in high levels of mortality and morbidity in patients. 1 MI is caused by a partial or complete obstruction of a coronary artery, resulting in significant reductions in coronary blood flow and in ischemia.2 MI injury results in loss of heart tissue, causing the heart to remodel structurally and metabolically. However, this remodeled state is unsustainable, and the heart eventually fails, where the myocardial wall thins, the left ventricular (LV) cavity dilates, and cardiac output decreases.2 After a MI, the progression into heart failure can be characterized by profound changes in myocardial energy metabolism. 1,3 Editorial see p 854 Clinical Perspective on p 904Fatty acid oxidation contributes 60% to 70% of the energy required for the resting heart, with glucose and lactate making up the majority of the remaining needs.1,2,4,5 The tightly regulated reciprocal relationship between glucose oxidation through pyruvate dehydrogenase (PDH) and fatty acid oxidation breaks down after an MI. [5][6][7] This is accompanied by alterations in both Krebs cycle enzyme activities and electron chain complexes and contributes to a generalized reduction in the capacity for ATP production. [8][9][10][11][12] In vitro experiments of MI have revealed that there are alterations in the electron transport chain as early as 2 weeks after MI, 8 and that alterations in cardiac mitochondrial metabolism continue out to 6 months. However, the exact nature and timing of in vivo mitochondrial dysfunction after an MI are unclear, and information about this would provide a greater understanding of the development of metabolic abnormalities after an MI.The use of hyperpolarized 13 C-magnetic resonance spectroscopy (MRS) 13 allows the study of in vivo mitochondrial metabolism by measuring the flux of 13 C-labeledBackground-Myocardial infarction (MI) is one of the leading causes of heart failure. An increasing body of evidence links alterations in cardiac metabolism and mitochondrial function with the progression of heart disease. The aim of this work was to, therefore, follow the in vivo mitochondrial metabolic alterations caused by MI, thereby allowing a greater understanding of the interplay between metabolic and functional abnormalities. Methods and Results-Using hyperpolarized carbon-13 ( 13 C)-magnetic resonance spectroscopy, in vivo alterations in mitochondrial metabolism were assessed for 22 weeks after surgically induced MI with reperfusion in female Wister rats. One week after MI, there were no detectable alterations in in vivo cardiac mitochondrial metabolism over the range of ejection fractions observed (from 28% to 84%). At 6 weeks after MI, in vivo mitochondrial Krebs cycle activity was impaired, with decreased 13 C-label flux into citrate, glutamate, and acetylcarnitine, which correlated with the degree of cardiac dysfunction. These changes were independent of alterations in pyruvate dehydrogenase flux. By 22 weeks, alterations were...

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“…Поэтому, изучая всю совокупность низкомолекулярных веществ, метаболомика всесторонне описывает молекулярный фенотип биологического объекта с предельно возможной степенью детализации и является неотъемлемой частью постгеномных исследований [1][2][3][4]. Посредством же анализа метаболитов, задействованных в патологических биохимических процессах, метаболомный анализ может использоваться в клинической практике для эффективной диагностики и расчета рисков заболеваний [3,[5][6][7].…”

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Metabolic profiling of human blood

2014

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Metabolomics is a novel “omics” branch of science intended for studying a comprehensive set of low molecular weight substances (metabolites) of various biological objects. Metabolite profiles represent a molecular phenotype of biological systems and reflect information encoded at the genome level and realized at the transcriptome and proteome levels. Analysis of human blood metabolic profile is universal and promising tool for clinical applications because it is a sensitive measure of both endogenous and exogenous (environmental) factors affected on the patient's organism. Technical implementation of metabolic profiling of blood and statistic analysis of metabolite profiles for effective diagnostics and risk assessments of diseases are discussed in this review.

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Metabolomics of the interaction between PPAR‐α and age in the PPAR‐α‐null mouse

Cited by 72 publications

References 42 publications

Increased Lipid Accumulation in Liver and White Adipose Tissue in Aging in the SAMP10 Mouse

Increased Lipid Accumulation in Liver and White Adipose Tissue in Aging in the SAMP10 Mouse

Impaired In Vivo Mitochondrial Krebs Cycle Activity After Myocardial Infarction Assessed Using Hyperpolarized Magnetic Resonance Spectroscopy

Metabolic profiling of human blood

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