ProQuest
Abstract/Details

The Role of Adiposity in the Association of Branched-Chain Amino Acids and Metabolic and Clinical Markers in Healthy Adults on Controlled Diets

Archer, Cairo.   University of Washington ProQuest Dissertations Publishing,  2021. 28961623.

Abstract (summary)

Branched-chain amino acids (BCAAs) leucine, isoleucine, and valine have been positively associated with adiposity and insulin resistance. Targeted metabolomic data from plasma samples of healthy adults (n = 40 men, n = 40 women) aged 18–45 years old derived from a randomized crossover feeding trial (Carbohydrates and Related Biomarkers-ClinicalTrials.gov Identifier: NCT00622661) were used to further elucidate why BCAAs are elevated in settings of increased adiposity and insulin resistance. Twelve metabolites were selected from a combination of a literature search and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway review for cross-sectional analysis. Linear mixed models were used to evaluate associations between (1) adiposity and metabolites related to BCAA catabolism, (2) adiposity, HOMA-IR, and CRP, and (3) markers of BCAA catabolism, adipokines (leptin and adiponectin), and markers of inflammation (CRP, IL-6, and SAA). Adiposity was positively associated with leucine (p = 0.043), isoleucine (p = 0.035), valine (p = 0.034), pyruvate (p = 0.015), alanine (p = 6e-4), glutamic acid (p = 8e-7), and isovaleric acid (p = 2e-4). Conversely, malonic acid concentration was found to be inversely associated with body adiposity (p = 0.014). These results support the hypothesis that elevated BCAAs are part of a metabolic signature of obesity and reductions in BCAA catabolism at the first two steps of BCAA catabolism likely drive elevations in plasma BCAA concentrations. Serum glucose, insulin, HOMA-IR score, and CRP were all positively associated with adiposity (p = 2.3e-3, p = 7.88e-6, p = 3.65e-6, p = 5e-3, respectively). These results were significant even after adjustments for plasma leucine, isoleucine, and valine concentration, and carbohydrate intake. Finally, plasma leptin was positively associated with leucine (p = 0.042), isoleucine (p = 0.045), valine (p = 0.021), and glutamic acid (p = 0.027) and these associations could be related to insulin resistance and regulation of plasma insulin levels. Leptin was inversely associated with malonic acid which may be related to the opposing roles leptin and malonic acid-derived malonyl-CoA play in fatty acid metabolism. These exploratory metabolomic results provide key connections between metabolites related to BCAA catabolism, adiposity, inflammation, and adipokine activity. These results have broad applications towards understanding the complex signaling effects of BCAAs on the human metabolome.

Indexing (details)


Psychology indexing term
Subject
Nutrition
Classification
0570: Nutrition
Identifier / keyword
BCAA; Branched-chain amino acids; Controlled feeding study; Insulin resistance; Obesity
Title
The Role of Adiposity in the Association of Branched-Chain Amino Acids and Metabolic and Clinical Markers in Healthy Adults on Controlled Diets
Author
Archer, Cairo
Number of pages
69
Publication year
2021
Degree date
2021
School code
0250
Source
MAI 83/7(E), Masters Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9798780639381
Advisor
Lampe, Johanna
Committee member
Navarro, Sandi; Kirk, Elizabeth
University/institution
University of Washington
Department
Nutritional Sciences
University location
United States -- Washington
Degree
Master's
Source type
Dissertation or Thesis
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
28961623
ProQuest document ID
2628318756
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
https://www.proquest.com/pqdtglobal/docview/2628318756/abstract/