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Restricting branched-chain amino acids within a high-fat diet prevents obesity

Citation

Liu, M and Huang, Y and Zhang, H and Aitken, D and Nevitt, MC and Rockel, JS and Pelletier, JP and Lewis, CE and Torner, J and Rampersaud, YR and Perruccio, AV and Mahomed, NN and Furey, A and Randell, EW and Rahman, P and Sun, G and Martel-Pelletier, J and Kapoor, M and Jones, G and Felson, D and Qi, D and Zhai, G, Restricting branched-chain amino acids within a high-fat diet prevents obesity, Metabolites, 12, (4) Article 334. ISSN 2218-1989 (2022) [Refereed Article]


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Copyright Statement

Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) license. (https://creativecommons.org/licenses/by/4.0/).

DOI: doi:10.3390/metabo12040334

Abstract

Obesity is a global pandemic, but there is yet no effective measure to control it. Recent metabolomics studies have identified a signature of altered amino acid profiles to be associated with obesity, but it is unclear whether these findings have actionable clinical potential. The aims of this study were to reveal the metabolic alterations of obesity and to explore potential strategies to mitigate obesity. We performed targeted metabolomic profiling of the plasma/serum samples collected from six independent cohorts and conducted an individual data meta-analysis of metabolomics for body mass index (BMI) and obesity. Based on the findings, we hypothesized that restriction of branched-chain amino acids (BCAAs), phenylalanine, or tryptophan may prevent obesity and tested our hypothesis in a dietary restriction trial with eight groups of 4-week-old male C57BL/6J mice (n = 5/group) on eight different types of diets, respectively, for 16 weeks. A total of 3397 individuals were included in the meta-analysis. The mean BMI was 30.7 ± 6.1 kg/m2, and 49% of participants were obese. Fifty-eight metabolites were associated with BMI and obesity (all p ≤ 2.58 × 10-4), linked to alterations of the BCAA, phenylalanine, tryptophan, and phospholipid metabolic pathways. The restriction of BCAAs within a high-fat diet (HFD) maintained the mice's weight, fat and lean volume, subcutaneous and visceral adipose tissue weight, and serum glucose and insulin at levels similar to those in the standard chow group, and prevented obesity, adipocyte hypertrophy, adipose inflammation, and insulin resistance induced by HFD. Our data suggest that four metabolic pathways, BCAA, phenylalanine, tryptophan, and phospholipid metabolic pathways, are altered in obesity and restriction of BCAAs within a HFD can prevent the development of obesity and insulin resistance in mice, providing a promising strategy to potentially mitigate diet-induced obesity.

Item Details

Item Type:Refereed Article
Keywords:branched-chain amino acids, meta-analysis, metabolomics, obesity, phenylalanine, tryptophan
Research Division:Biomedical and Clinical Sciences
Research Group:Nutrition and dietetics
Research Field:Public health nutrition
Objective Division:Health
Objective Group:Clinical health
Objective Field:Treatment of human diseases and conditions
UTAS Author:Aitken, D (Associate Professor Dawn Aitken)
UTAS Author:Jones, G (Professor Graeme Jones)
ID Code:154042
Year Published:2022
Web of Science® Times Cited:2
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-10-25
Last Modified:2022-11-01
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