Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents Obesity
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/12/4/334 |
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| author | Ming Liu 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 Guangju Zhai |
| author_facet | Ming Liu 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 Guangju Zhai |
| author_sort | Ming Liu |
| collection | DOAJ |
| description | 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/m<sup>2</sup>, and 49% of participants were obese. Fifty-eight metabolites were associated with BMI and obesity (all <i>p</i> ≤ 2.58 × 10<sup>−4</sup>), 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. |
| first_indexed | 2024-03-09T10:32:24Z |
| format | Article |
| id | doaj.art-be8a85981d014df1aab4161b6a3b1d68 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T10:32:24Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-be8a85981d014df1aab4161b6a3b1d682023-12-01T21:13:38ZengMDPI AGMetabolites2218-19892022-04-0112433410.3390/metabo12040334Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents ObesityMing Liu0Yiheng Huang1Hongwei Zhang2Dawn Aitken3Michael C. Nevitt4Jason S. Rockel5Jean-Pierre Pelletier6Cora E. Lewis7James Torner8Yoga Raja Rampersaud9Anthony V. Perruccio10Nizar N. Mahomed11Andrew Furey12Edward W. Randell13Proton Rahman14Guang Sun15Johanne Martel-Pelletier16Mohit Kapoor17Graeme Jones18David Felson19Dake Qi20Guangju Zhai21Division of Biomedical Sciences (Genetics), Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaCollege of Pharmacy, University of Manitoba, Winnipeg, MB R3E 0T5, CanadaDiscipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaMenzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, AustraliaDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA 94158, USAOsteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON M5T 2S8, CanadaOsteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, QC H2X 0A9, CanadaDepartment of Epidemiology, University of Alabama, Birmingham, AL 35233, USADepartment of Epidemiology, University of Iowa, Iowa City, IA 52242, USAOsteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON M5T 2S8, CanadaOsteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON M5T 2S8, CanadaOsteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON M5T 2S8, CanadaDiscipline of Surgery, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaDiscipline of Laboratory Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaDiscipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaDiscipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaOsteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, QC H2X 0A9, CanadaOsteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON M5T 2S8, CanadaMenzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, AustraliaDepartment of Rheumatology, Boston University School of Medicine, Boston, MA 02118, USACollege of Pharmacy, University of Manitoba, Winnipeg, MB R3E 0T5, CanadaDivision of Biomedical Sciences (Genetics), Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaObesity 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/m<sup>2</sup>, and 49% of participants were obese. Fifty-eight metabolites were associated with BMI and obesity (all <i>p</i> ≤ 2.58 × 10<sup>−4</sup>), 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.https://www.mdpi.com/2218-1989/12/4/334obesitymetabolomicsmeta-analysisbranched-chain amino acidsphenylalaninetryptophan |
| spellingShingle | Ming Liu 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 Guangju Zhai Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents Obesity Metabolites obesity metabolomics meta-analysis branched-chain amino acids phenylalanine tryptophan |
| title | Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents Obesity |
| title_full | Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents Obesity |
| title_fullStr | Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents Obesity |
| title_full_unstemmed | Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents Obesity |
| title_short | Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents Obesity |
| title_sort | restricting branched chain amino acids within a high fat diet prevents obesity |
| topic | obesity metabolomics meta-analysis branched-chain amino acids phenylalanine tryptophan |
| url | https://www.mdpi.com/2218-1989/12/4/334 |
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