Metabolic Profiling of Visceral and Subcutaneous Adipose Tissue from Colorectal Cancer Patients: GC-TOF MS analyis of subcutaneous and visceral adipose tissue samples
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Adipose Tissue
PROVIDER: ST000061 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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Project description:This West Coast Metabolomics Center pilot and feasibility project was granted to Johanna Lampe (Fred Hutchinson Cancer Research Center at Univ. of Washington, Seattle). In the current investigation, unbiased profiling of the metabolome and lipidome of adipose tissue samples (visceral(VAT) and subcutaenous (SAT)) and serum of 50 CRC patients, including stages I-IV, from the Fred Hutchinson Cancer Center (Seattle,WA) and the German Cancer Research Center (Heidelberg, Germany) was conducted. The lipidome and metabolome of adipose tissue (VAT/SAT) and serum were analyzed using established UPLC-QTOFMS analysis and GC-TOFMS analyses, respectively.
The primary objectives of this project were to 1) compare the metabolome and lipidome of matched VAT and SAT adipose tissue of n=50 Colorectal Cancer Cell (CRC) patients, 2) characterize the associations between the lipidome and metabolome in adipose tissue (VAT/SAT) and serum of n=50 CRC patients and 3) test the associations between the lipidome/metabolome of VAT and serum with the tumor stage of CRC patients.
2019-07-01 | MSV000084042 | GNPS
Project description:Humans interact with thousands of chemicals. This study aims to identify substances of emerging concern and in need of human health risk evaluations. Sixteen pooled human serum samples were constructed from 25 individual samples each from the National Institute of Environmental Health Sciences' Clinical Research Unit. Samples were analyzed using gas chromatography (GC) × GC/time-of-flight (TOF)-mass spectrometry (MS) in a suspect screening analysis, with follow-up confirmation analysis of 19 substances. A standard reference material blood sample was also analyzed through the confirmation process for comparison. The pools were stratified by sex (female and male) and by age (≤45 and >45). Publicly available information on potential exposure sources was aggregated to annotate presence in serum as either endogenous, food/nutrient, drug, commerce, or contaminant. Of the 544 unique substances tentatively identified by spectral matching, 472 were identified in females, while only 271 were identified in males. Surprisingly, 273 of the identified substances were found only in females. It is known that behavior and near-field environments can drive exposures, and this work demonstrates the existence of exposure sources uniquely relevant to females.
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Project description:Background and aimsAccumulation of visceral adipose tissue is associated with hepatic inflammation and fibrosis, suggestive of its metabolic and inflammatory properties. We aimed to examine the histologic findings of visceral and subcutaneous adipose tissue and to associate these findings with clinical and radiologic characteristics in patients with cirrhosis.MethodsIncluded were 55 adults with cirrhosis who underwent liver transplantation from 3/2017-12/2018 and had an abdominal computed tomography (CT) scan within 6 months prior to transplant. Visceral-to-subcutaneous adipose tissue ratio (VSR) was calculated using visceral (VATI) and subcutaneous adipose tissue index (SATI) quantified by CT at the L3-vertebral level and normalized for height (cm2/m2). VAT (greater omentum), SAT (abdominal wall), and skeletal muscle (rectus abdominis) biopsies were collected at transplant.ResultsMajority of patients had VAT inflammation (71%); only one patient (2%) had SAT inflammation. Patients with VAT inflammation had similar median VATI (42 vs 41 cm2/m2), lower median SATI (64 vs 97 cm2/m2), and higher median VSR (0.63 vs 0.37, p = 0.002) than patients without inflammation. In univariable logistic regression, VSR was associated with VAT inflammation (OR 1.47, 95%CI 1.11-1.96); this association remained significant even after adjusting for age, sex, BMI, HCC, or MELD-Na on bivariable analyses.ConclusionIn patients with cirrhosis undergoing liver transplantation, histologic VAT inflammation was common, but SAT inflammation was not. Increased VSR was independently associated with VAT inflammation. Given the emerging data demonstrating the prognostic value of VSR, our findings support the value of CT-quantified VSR as a prognostic marker for adverse outcomes in the liver transplant setting.
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Project description:Obesity is a complex multifactorial phenotype that influences several metabolic pathways. Yet, few studies have examined the relations of different body fat compartments to urinary and serum metabolites. Anthropometric phenotypes (visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), the ratio between VAT and SAT (VSR), body mass index (BMI), waist circumference (WC)) and urinary and serum metabolite concentrations measured by nuclear magnetic resonance spectroscopy were measured in a population-based sample of 228 healthy adults. Multivariable linear and logistic regression models, corrected for multiple testing using the false discovery rate, were used to associate anthropometric phenotypes with metabolites. We adjusted for potential confounding variables: age, sex, smoking, physical activity, menopausal status, estimated glomerular filtration rate (eGFR), urinary glucose, and fasting status. In a fully adjusted logistic regression model dichotomized for the absence or presence of quantifiable metabolite amounts, VAT, BMI and WC were inversely related to urinary choline (ß = -0.18, p = 2.73*10-3), glycolic acid (ß = -0.20, 0.02), and guanidinoacetic acid (ß = -0.12, p = 0.04), and positively related to ethanolamine (ß = 0.18, p = 0.02) and dimethylamine (ß = 0.32, p = 0.02). BMI and WC were additionally inversely related to urinary glutamine and lactic acid. Moreover, WC was inversely associated with the detection of serine. VAT, but none of the other anthropometric parameters, was related to serum essential amino acids, such as valine, isoleucine, and phenylalanine among men. Compared to other adiposity measures, VAT demonstrated the strongest and most significant relations to urinary and serum metabolites. The distinct relations of VAT, SAT, VSR, BMI, and WC to metabolites emphasize the importance of accurately differentiating between body fat compartments when evaluating the potential role of metabolic regulation in the development of obesity-related diseases, such as insulin resistance, type 2 diabetes, and cardiovascular disease.
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Project description:There is a link between visceral white adipose tissue (WAT) and the metabolic syndrome in humans, with health improvements produced with small visceral WAT reduction. By contrast, subcutaneous WAT provides a site for lipid storage that is rather innocuous relative to ectopic lipid storage in muscle or liver. The sympathetic nervous system (SNS) is the principal initiator for lipolysis in WAT by mammals. Nothing is known, however, about the central origins of the SNS circuitry innervating the only true visceral WAT in rodents, mesenteric WAT (MWAT), which drains into the hepatic portal vein. We tested whether the central sympathetic circuits to subcutaneous [inguinal WAT (IWAT)] and visceral WAT (MWAT) are separate or shared and whether they possess differential sympathetic drives with food deprivation in Siberian hamsters. Using two isogenic strains of pseudorabies virus, a retrograde transneuronal viral tract tracer within the same hamsters, we found some overlap (∼20-55% doubly infected neurons) between the two circuitries across the neural axis with lesser overlap proximal to the depots (spinal cord and sympathetic chain) and with more neurons involved in the innervation of IWAT than MWAT in some brain regions. Food deprivation triggered a greater sympathetic drive to subcutaneous (IWAT) than visceral (MWAT) depots. Collectively, we demonstrated both shared and separate populations of brain, spinal cord, and sympathetic chain neurons ultimately project to a subcutaneous WAT depot (IWAT) and the only visceral WAT depot in rodents (MWAT). In addition, the lipolytic stimulus of food deprivation only increased SNS drive to subcutaneous fat (IWAT).
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2014-09-17 | GSE61454 | GEO
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