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

Metabolites

Dake Qi¹  Yiheng Huang¹  Michael C. Nevitt²  Cora E. Lewis³  James Torner⁴  David Felson⁵  Edward W. Randell⁶  Hongwei Zhang⁷  Guang Sun⁷  Proton Rahman⁷  Andrew Furey⁸  Ming Liu⁹  Guangju Zhai⁹  Dawn Aitken^1,10  Graeme Jones^1,10  Anthony V. Perruccio^1,11  Yoga Raja Rampersaud^1,11  Mohit Kapoor^1,11  Jason S. Rockel^1,11  Nizar N. Mahomed^1,11  Jean-Pierre Pelletier^1,12  Johanne Martel-Pelletier^1,12 

[1] College of Pharmacy, University of Manitoba, Winnipeg, MB R3E 0T5, Canada;Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94158, USA;Department of Epidemiology, University of Alabama, Birmingham, AL 35233, USA;Department of Epidemiology, University of Iowa, Iowa City, IA 52242, USA;Department of Rheumatology, Boston University School of Medicine, Boston, MA 02118, USA;Discipline of Laboratory Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, Canada;Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, Canada;Discipline of Surgery, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, Canada;Division of Biomedical Sciences (Genetics), Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, Canada;Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia;Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON M5T 2S8, Canada;Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, QC H2X 0A9, Canada;

关键词: obesity;    metabolomics;    meta-analysis;    branched-chain amino acids;    phenylalanine;    tryptophan;   

DOI  :  10.3390/metabo12040334

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown