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Alterations of plasma metabolite profiles related to adipose tissue distribution and cardiometabolic risk.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2015 Oct 15; Vol. 309 (8), pp. E736-46. Date of Electronic Publication: 2015 Aug 25. - Publication Year :
- 2015
-
Abstract
- Metabolomic profiling of obese individuals revealed altered concentrations of many metabolites, especially branched-chain amino acids (BCAA), possibly linked to altered adipose tissue BCAA catabolism. We tested the hypothesis that some features of this metabolite signature relate closely to visceral obesity and concomitant alterations in cardiometabolic risk factors. We also postulated that alterations in BCAA-catabolizing enzymes are predominant in visceral adipose tissue. Fifty-nine women (BMI 20-41 kg/m(2)) undergoing gynecologic surgery were recruited and characterized for overall and regional adiposity, blood metabolite levels using targeted metabolomics, and cardiometabolic risk factors. Adipose samples (visceral and subcutaneous) were obtained and used for gene expression and Western blot analyses. Obese women had significantly higher circulating BCAA and kynurenine/tryptophan (Kyn/Trp) ratio than lean or overweight women (P < 0.01). Principal component analysis confirmed that factors related to AA and the Kyn/Trp ratio were positively associated with BMI, fat mass, visceral or subcutaneous adipose tissue area, and subcutaneous adipocyte size (P ≤ 0.05). AA-related factor was positively associated with HOMA-IR (P ≤ 0.01). Factors reflecting glycerophospholipids and sphingolipids levels were mostly associated with altered blood lipid concentrations (P ≤ 0.05). Glutamate level was the strongest independent predictor of visceral adipose tissue area (r = 0.46, P < 0.001). Obese women had lower expression and protein levels of BCAA-catabolizing enzymes in visceral adipose tissue than overweight or lean women (P ≤ 0.05). We conclude that among metabolites altered in obesity plasma concentrations of BCAA and the Kyn/Trp ratio are closely related to increased adiposity. Alterations in expression and protein levels of BCAA-catabolizing enzymes are predominant in visceral adipose tissue.<br /> (Copyright © 2015 the American Physiological Society.)
- Subjects :
- 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) genetics
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) metabolism
Adipocytes pathology
Adipokines metabolism
Adult
Amino Acids metabolism
Blood Glucose metabolism
Blotting, Western
Cell Size
Cholesterol, HDL metabolism
Cholesterol, LDL metabolism
Dyslipidemias metabolism
Female
Gene Expression Profiling
Humans
Insulin Resistance
Intra-Abdominal Fat metabolism
Kynurenine metabolism
Metabolomics
Middle Aged
Overweight metabolism
Risk Factors
Subcutaneous Fat metabolism
Thinness metabolism
Triglycerides metabolism
Tryptophan metabolism
Adipose Tissue metabolism
Amino Acids, Branched-Chain metabolism
Body Fat Distribution
Cardiovascular Diseases metabolism
Obesity metabolism
RNA, Messenger metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1555
- Volume :
- 309
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 26306599
- Full Text :
- https://doi.org/10.1152/ajpendo.00231.2015