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

2006 ◽  
Vol 27 (2) ◽  
pp. 178-186 ◽  
Author(s):  
Helen J. Atherton ◽  
Nigel J. Bailey ◽  
Wen Zhang ◽  
John Taylor ◽  
Hilary Major ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Nmr Spectroscopy ◽  
Magic Angle Spinning ◽  
Magic Angle ◽  
H Nmr ◽  
The Metabolic Syndrome ◽  
Chromatography Mass Spectrometry ◽  
Metabolic Role

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 β-oxidation in the liver, in part under the regulation of peroxisome proliferator-activated receptor-α (PPAR-α). A failure to express PPAR-α 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-α has been investigated in heart, skeletal muscle, liver, and adipose tissue of PPAR-α null mice at 1 mo of age using metabolomics. To maximize the coverage of the metabolome in these tissues, 1H-NMR spectroscopy, magic angle spinning 1H-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-α results in perturbations in glycolysis, the citric acid cycle, and gluconeogenesis. Furthermore, despite PPAR-α being weakly expressed in adipose tissue, a profound metabolic perturbation was detected in this tissue.

Metabolic profile of intact tissue from uterine leiomyomas using high-resolution magic-angle-spinning 1 H NMR spectroscopy

2010 ◽  
Vol 23 (10) ◽  
pp. 1137-1145 ◽  
Author(s):  
Pierluigi Mazzei ◽  
Alessandro Piccolo ◽  
Loredana Nugnes ◽  
Massimo Mascolo ◽  
Gaetano De Rosa ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
High Resolution ◽  
Metabolic Profile ◽  
Magic Angle Spinning ◽  
Uterine Leiomyomas ◽  
Magic Angle ◽  
Intact Tissue ◽  
H Nmr ◽  
Angle Spinning

scholarly journals The biochemical profile of rat testicular tissue as measured by magic angle spinning 1 H NMR spectroscopy

FEBS Letters ◽  
2000 ◽  
Vol 486 (3) ◽  
pp. 225-229 ◽  
Author(s):  
J.L. Griffin ◽  
J. Troke ◽  
L.A. Walker ◽  
R.F. Shore ◽  
J.C. Lindon ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Testicular Tissue ◽  
Magic Angle Spinning ◽  
Magic Angle ◽  
Biochemical Profile ◽  
H Nmr ◽  
Angle Spinning

scholarly journals Monitoring apoptosis in intact cells by high‐resolution magic angle spinning 1 H NMR spectroscopy

2021 ◽  
Author(s):  
Marta Wylot ◽  
David T.E. Whittaker ◽  
Stephen A.C. Wren ◽  
John H. Bothwell ◽  
Leslie Hughes ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
High Resolution ◽  
Magic Angle Spinning ◽  
Magic Angle ◽  
Intact Cells ◽  
H Nmr ◽  
Angle Spinning

Defining a metabolic phenotype in the brain of a transgenic mouse model of spinocerebellar ataxia 3

2004 ◽  
Vol 16 (3) ◽  
pp. 334-340 ◽  
Author(s):  
J. L. Griffin ◽  
C. K. Cemal ◽  
M. A. Pook
Keyword(s):  
Pattern Recognition ◽  
Nmr Spectroscopy ◽  
Mouse Model ◽  
Yeast Artificial Chromosome ◽  
Magic Angle Spinning ◽  
Metabolic Phenotype ◽  
Magic Angle ◽  
Spinocerebellar Ataxias ◽  
H Nmr

Many of the spinocerebellar ataxias (SCAs) are caused by expansions of CAG trinucleotide repeats encoding abnormal stretches of polyglutamine. SCA3 or Machado-Joseph disease (MJD) is the commonest dominant inherited ataxia disease, with pathological phenotypes apparent with a CAG triplet repeat length of 61–84. In this study a mouse model of SCA3 has been examined which was produced using a human yeast artificial chromosome containing the MJD gene with a CAG triplet expansion of 84 repeats. These mice have previously been shown to possess a mild progressive cerebellar deficit. NMR-based metabolomics/metabonomics in conjunction with multivariate pattern recognition identified a number of metabolic perturbations in SCA3 mice. These changes included a consistent increase in glutamine concentration in tissue extracts of the cerebellum and cerebrum and spectra obtained from intact tissue using magic angle spinning 1H-NMR spectroscopy. Furthermore, these profiles demonstrated metabolic abnormalities were present in the cerebrum, a region not previously implicated in SCA3. As well as an increase in glutamine both brain regions demonstrated decreases in GABA, choline, phosphocholine and lactate (representing the summation of lactate in vivo, and postmortem glycolysis of glucose and glycogen). The metabolic changes are discussed in terms of the formation of neuronal intranuclear inclusions associated with SCA3. This study suggests high-resolution 1H-NMR spectroscopy coupled with pattern recognition may provide a rapid method for assessing the phenotype of animal models of human disease.

Brown adipose tissue: a potential target in the fight against obesity and the metabolic syndrome

2015 ◽  
Vol 129 (11) ◽  
pp. 933-949 ◽  
Author(s):  
Laurence Poekes ◽  
Nicolas Lanthier ◽  
Isabelle A. Leclercq
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Potential Contribution ◽  
Atp Production ◽  
Main Site ◽  
Glucose Homoeostasis ◽  
The Metabolic Syndrome ◽  
Metabolic Role ◽  
Brown Adipose

BAT (brown adipose tissue) is the main site of thermogenesis in mammals. It is essential to ensure thermoregulation in newborns. It is also found in (some) adult humans. Its capacity to oxidize fatty acids and glucose without ATP production contributes to energy expenditure and glucose homoeostasis. Brown fat activation has thus emerged as an attractive therapeutic target for the treatment of obesity and the metabolic syndrome. In the present review, we integrate the recent advances on the metabolic role of BAT and its relation with other tissues as well as its potential contribution to fighting obesity and the metabolic syndrome.

scholarly journals Metabolic profiling of visceral adipose tissue from obese subjects with or without metabolic syndrome

2018 ◽  
Vol 475 (5) ◽  
pp. 1019-1035 ◽  
Author(s):  
Eleonora Candi ◽  
Manfredi Tesauro ◽  
Carmine Cardillo ◽  
Anna Maria Lena ◽  
Francesca Schinzari ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mass Spectrometry ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Vascular Complications ◽  
Gas Chromatography Mass Spectrometry ◽  
Chromatography Mass Spectrometry ◽  
Obese Subjects ◽  
Visceral Adipose

Obesity represents one of the most complex public health challenges and has recently reached epidemic proportions. Obesity is also considered to be primarily responsible for the rising prevalence of metabolic syndrome, defined as the coexistence in the same individual of several risk factors for atherosclerosis, including dyslipidemia, hypertension and hyperglycemia, as well as for cancer. Additionally, the presence of three of the five risk factors (abdominal obesity, low high-density lipoprotein cholesterol, high triglycerides, high fasting glucose and high blood pressure) characterizes metabolic syndrome, which has serious clinical consequences. The current study was conducted in order to identify metabolic differences in visceral adipose tissue (VAT) collected from obese (body mass index 43–48) human subjects who were diagnosed with metabolic syndrome, obese individuals who were metabolically healthy and nonobese healthy controls. Extensive gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS/MS) analyses were used to obtain the untargeted VAT metabolomic profiles of 481 metabolites belonging to all biochemical pathways. Our results indicated consistent increases in oxidative stress markers from the pathologically obese samples in addition to subtle markers of elevated glucose levels that may be consistent with metabolic syndrome. In the tissue derived from the pathologically obese subjects, there were significantly elevated levels of plasmalogens, which may be increased in response to oxidative changes in addition to changes in glycerolphosphorylcholine, glycerolphosphorylethanolamine glycerolphosphorylserine, ceramides and sphingolipids. These data could be potentially helpful for recognizing new pathways that underlie the metabolic–vascular complications of obesity and may lead to the development of innovative targeted therapies.

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