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Article

Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents Obesity

1
Division of Biomedical Sciences (Genetics), Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, Canada
2
College of Pharmacy, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
3
Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, Canada
4
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia
5
Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94158, USA
6
Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON M5T 2S8, Canada
7
Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, QC H2X 0A9, Canada
8
Department of Epidemiology, University of Alabama, Birmingham, AL 35233, USA
9
Department of Epidemiology, University of Iowa, Iowa City, IA 52242, USA
10
Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 2S8, Canada
11
Department of Surgery, University of Toronto, Toronto, ON M5T 2S8, Canada
12
Discipline of Surgery, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, Canada
13
Office of the Premier, Government of Newfoundland and Labrador, St. John’s, NL A1B 4J6, Canada
14
Discipline of Laboratory Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, Canada
15
Department of Rheumatology, Boston University School of Medicine, Boston, MA 02118, USA
16
NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Victor Gault
Metabolites 2022, 12(4), 334; https://doi.org/10.3390/metabo12040334
Received: 18 March 2022 / Revised: 1 April 2022 / Accepted: 4 April 2022 / Published: 7 April 2022
(This article belongs to the Special Issue Metabolomics of Complex Traits II)
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. View Full-Text
Keywords: obesity; metabolomics; meta-analysis; branched-chain amino acids; phenylalanine; tryptophan obesity; metabolomics; meta-analysis; branched-chain amino acids; phenylalanine; tryptophan
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MDPI and ACS Style

Liu, M.; Huang, Y.; Zhang, H.; Aitken, D.; Nevitt, M.C.; Rockel, J.S.; Pelletier, J.-P.; Lewis, C.E.; Torner, J.; Rampersaud, Y.R.; Perruccio, A.V.; Mahomed, N.N.; Furey, A.; Randell, E.W.; Rahman, P.; Sun, G.; Martel-Pelletier, J.; Kapoor, M.; Jones, G.; Felson, D.; Qi, D.; Zhai, G. Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents Obesity. Metabolites 2022, 12, 334. https://doi.org/10.3390/metabo12040334

AMA Style

Liu M, Huang Y, Zhang H, Aitken D, Nevitt MC, Rockel JS, Pelletier J-P, Lewis CE, Torner J, Rampersaud YR, Perruccio AV, Mahomed NN, Furey A, Randell EW, Rahman P, Sun G, Martel-Pelletier J, Kapoor M, Jones G, Felson D, Qi D, Zhai G. Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents Obesity. Metabolites. 2022; 12(4):334. https://doi.org/10.3390/metabo12040334

Chicago/Turabian Style

Liu, Ming, Yiheng Huang, Hongwei Zhang, Dawn Aitken, Michael C. Nevitt, Jason S. Rockel, Jean-Pierre Pelletier, Cora E. Lewis, James Torner, Yoga Raja Rampersaud, Anthony V. Perruccio, Nizar N. Mahomed, Andrew Furey, Edward W. Randell, Proton Rahman, Guang Sun, Johanne Martel-Pelletier, Mohit Kapoor, Graeme Jones, David Felson, Dake Qi, and Guangju Zhai. 2022. "Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents Obesity" Metabolites 12, no. 4: 334. https://doi.org/10.3390/metabo12040334

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