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| Status |
Public on Mar 11, 2019 |
| Title |
Branched chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Elevated branched chain amino acids (BCAAs) are associated with obesity and insulin resistance. How long-term dietary BCAAs impact late-life health and lifespan is unknown. Here, we show that when dietary BCAAs are varied against a fixed, isocaloric macronutrient background, long-term exposure to high BCAA diets led to hyperphagia, obesity and reduced lifespan. These effects were not due to elevated BCAA per se or hepatic mTOR activation, but rather the shift in balance between dietary BCAAs and other AAs, notably tryptophan and threonine. Increasing the ratio of BCAAs to these AAs resulted in hyperphagia and was linked to central serotonin depletion. Preventing hyperphagia by calorie restriction or pair-feeding averted the health costs of a high BCAA diet. Our data highlight a role for amino acid quality in energy balance and show that health costs of chronic high BCAA intakes were not due to intrinsic toxicity; rather, to hyperphagia driven by AA imbalance.
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| Overall design |
3 animals per sex per diet were used. Mice were fed one of four diets (all 19% total protein, 63% carbohydrate, 18% fat, total energy density 14 kJ/g) varying in BCAA content (BCAA200: twice BCAA content of control diet AIN93G; BCAA100: standard content of BCAAs; and BCAA50 and BCAA20: containing one half and one fifth of standard content of BCAAs), and either euthanized at 15 months of age or maintained for determination of lifespan.
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| Contributor(s) |
Solon-Biet SM, Cogger VC, Pulpitel T, Wahl D, Clark X, Senior AM, Wang Q, Brandon A, Perks R, O’Sullivan J, Koay YC, Bell-Anderson K, Kebede M, Yau B, Atkinson C, Svineng G, Ribeiro R, Wali JA, Piper MD, Cumming RG, Hirani V, Handelsman DJ, Juricic P, Partridge L, Raubenheimer D, Cooney G, Le Couteur DG, Simpson SJ |
| Citation(s) |
31656947 |
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| Submission date |
May 24, 2018 |
| Last update date |
Nov 04, 2019 |
| Contact name |
Qiao-Ping Wang |
| E-mail(s) |
qpwang1@gmail.com
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| Phone |
61292958304
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| Organization name |
University of Sydney
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| Department |
Charles Perkins Centre
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| Lab |
Functional Genomics
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| Street address |
Johns Hopkins Dr
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| City |
Sydney |
| State/province |
NSW |
| ZIP/Postal code |
2046 |
| Country |
Australia |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA472872 |
| SRA |
SRP148854 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE114855_FPKM_Pearson_GEO.xlsx |
4.3 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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