Metabolomics Profiling of Visceral Adipose Tissue: Results From MESA and the NEO Study

Autor: Matthew A. Allison, David M. Herrington, Ibrahim Karaman, Ioanna Tzoulaki, Philip Greenland, Claire L. Boulangé, Roelof A.J. Smit, Ian J. Neeland, Dennis O. Mook-Kanamori, Renée de Mutsert, Naresh M. Punjabi, Hildo J. Lamb, J. Wouter Jukema, Ko Willems van Dijk, Sebastiaan C. Boone, Frits R. Rosendaal, Colby Ayers, Dhananjay Vaidya
Přispěvatelé: Imperial College Healthcare NHS Trust- BRC Funding, National Institutes of Health
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
obesity
Epidemiology
Metabolite
Glutamine
Proton Magnetic Resonance Spectroscopy
Adipose tissue
Cardiorespiratory Medicine and Haematology
030204 cardiovascular system & hematology
chemistry.chemical_compound
0302 clinical medicine
80 and over
visceral adipose tissue
Amino Acids
Tomography
Original Research
2. Zero hunger
Aged
80 and over
0303 health sciences
cohort
Organ Size
Middle Aged
Magnetic Resonance Imaging
X-Ray Computed
3. Good health
adipose tissue
Cholesterol
Female
Cardiology and Cardiovascular Medicine
Glycolysis
Metabolic Networks and Pathways
medicine.medical_specialty
HDL
metabolite
Intra-Abdominal Fat
LDL
03 medical and health sciences
Metabolomics
Internal medicine
medicine
Humans
Lactic Acid
Metabolic and endocrine
Triglycerides
Nutrition
030304 developmental biology
Aged
business.industry
Prevention
Cholesterol
HDL
Gluconeogenesis
Metabolism
Cholesterol
LDL
Branched-Chain
Endocrinology
chemistry
Linear Models
Digestive Diseases
business
Tomography
X-Ray Computed
Biomarkers
Amino Acids
Branched-Chain
Lipoprotein
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Journal of the American Heart Association
Journal of the American Heart Association, 8(9). WILEY
Journal of the American Heart Association, vol 8, iss 9
ISSN: 2047-9980
Popis: Background Identifying associations between serum metabolites and visceral adipose tissue ( VAT ) could provide novel biomarkers of VAT and insights into the pathogenesis of obesity‐related diseases. We aimed to discover and replicate metabolites reflecting pathways related to VAT . Methods and Results Associations between fasting serum metabolites and VAT area (by computed tomography or magnetic resonance imaging) were assessed with cross‐sectional linear regression of individual‐level data from participants in MESA (Multi‐Ethnic Study of Atherosclerosis; discovery, N=1103) and the NEO (Netherlands Epidemiology of Obesity) study (replication, N=2537). Untargeted 1 H nuclear magnetic resonance metabolomics profiling of serum was performed in MESA, and metabolites were replicated in the NEO study using targeted 1 H nuclear magnetic resonance spectroscopy. A total of 30 590 metabolomic spectral variables were evaluated. After adjustment for age, sex, race/ethnicity, socioeconomic status, smoking, physical activity, glucose/lipid‐lowering medication, and body mass index, 2104 variables representing 24 nonlipid and 49 lipid/lipoprotein subclass metabolites remained significantly associated with VAT ( P =4.88×10 −20 –1.16×10 −3 ). These included conventional metabolites, amino acids, acetylglycoproteins, intermediates of glucose and hepatic metabolism, organic acids, and subclasses of apolipoproteins, cholesterol, phospholipids, and triglycerides. Metabolites mapped to 31 biochemical pathways, including amino acid substrate use/metabolism and glycolysis/gluconeogenesis. In the replication cohort, acetylglycoproteins, branched‐chain amino acids, lactate, glutamine (inversely), and atherogenic lipids remained associated with VAT ( P =1.90×10 −35 –8.46×10 −7 ), with most associations remaining after additional adjustment for surrogates of VAT (glucose level, waist circumference, and serum triglycerides), reflecting novel independent associations. Conclusions We identified and replicated a metabolite panel associated with VAT in 2 community‐based cohorts. These findings persisted after adjustment for body mass index and appear to define a metabolic signature of visceral adiposity.
Databáze: OpenAIRE
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