NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet 387, 1377–1396 (2016).
Stierman, B. et al. National Health and Nutrition Examination Survey 2017–March 2020 Prepandemic Data Files—Development of Files and Prevalence Estimates for Selected Health Outcomes National Health Statistics Reports no. 158 (CDC, 2021).
Fontana, L. et al. Decreased consumption of branched-chain amino acids improves metabolic health. Cell Rep. 16, 520–530 (2016).
Samaha, F. F. et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. N. Engl. J. Med. 348, 2074–2081 (2003).
Stolt, E. et al. Sulfur amino acid restriction, energy metabolism and obesity: a study protocol of an 8-week randomized controlled dietary intervention with whole foods and amino acid supplements. J. Transl. Med. 19, 153 (2021).
Yancy, W. S. Jr, Olsen, M. K., Guyton, J. R., Bakst, R. P. & Westman, E. C. A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann. Intern. Med. 140, 769–777 (2004).
Coll, A. P. et al. GDF15 mediates the effects of metformin on body weight and energy balance. Nature 578, 444–448 (2020).
Fisher, F. M. & Maratos-Flier, E. Understanding the Physiology of FGF21. Annu. Rev. Physiol. 78, 223–241 (2016).
Suriben, R. et al. Antibody-mediated inhibition of GDF15-GFRAL activity reverses cancer cachexia in mice. Nat. Med. 26, 1264–1270 (2020).
Smith, C. M., Narrow, C. M., Kendrick, Z. V. & Steffen, C. The effect of pantothenate deficiency in mice on their metabolic response to fast and exercise. Metabolism 36, 115–121 (1987).
Rose, W. C. The nutritive significance of the amino acids and certain related compounds. Science 86, 298–300 (1937).
Ishii, I. et al. Cystathionine gamma-lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury. J. Biol. Chem. 285, 26358–26368 (2010).
Mani, S., Yang, G. & Wang, R. A critical life-supporting role for cystathionine gamma-lyase in the absence of dietary cysteine supply. Free Radic. Biol. Med. 50, 1280–1287 (2011).
Du, Y., Meng, Q., Zhang, Q. & Guo, F. Isoleucine or valine deprivation stimulates fat loss via increasing energy expenditure and regulating lipid metabolism in WAT. Amino Acids 43, 725–734 (2012).
Guo, F. & Cavener, D. R. The GCN2 eIF2α kinase regulates fatty-acid homeostasis in the liver during deprivation of an essential amino acid. Cell Metab. 5, 103–114 (2007).
Xiao, F. et al. Effects of essential amino acids on lipid metabolism in mice and humans. J. Mol. Endocrinol. 57, 223–231 (2016).
Xiao, F. & Guo, F. Impacts of essential amino acids on energy balance. Mol. Metab. 57, 101393 (2022).
Zhang, X. et al. Dietary tryptophan, tyrosine, and phenylalanine depletion induce reduced food intake and behavioral alterations in mice. Physiol. Behav. 244, 113653 (2022).
Hao, S. et al. Uncharged tRNA and sensing of amino acid deficiency in mammalian piriform cortex. Science 307, 1776–1778 (2005).
Day, E. A. et al. Metformin-induced increases in GDF15 are important for suppressing appetite and promoting weight loss. Nat. Metab. 1, 1202–1208 (2019).
Kilberg, M. S., Shan, J. & Su, N. ATF4-dependent transcription mediates signaling of amino acid limitation. Trends Endocrinol. Metab. 20, 436–443 (2009).
Kim, K. H. et al. Metformin-induced inhibition of the mitochondrial respiratory chain increases FGF21 expression via ATF4 activation. Biochem. Biophys. Res. Commun. 440, 76–81 (2013).
Gusarov, I. et al. Dietary thiols accelerate aging of C. elegans. Nat. Commun. 12, 4336 (2021).
Jonsson, W. O., Margolies, N. S. & Anthony, T. G. Dietary sulfur amino acid restriction and the integrated stress response: mechanistic insights. Nutrients https://doi.org/10.3390/nu11061349 (2019).
Miller, R. A. et al. Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell 4, 119–125 (2005).
Richie, J. P. Jr et al. Methionine restriction increases blood glutathione and longevity in F344 rats. FASEB J. 8, 1302–1307 (1994).
Lu, S. C. Glutathione synthesis. Biochim. Biophys. Acta 1830, 3143–3153 (2013).
Jackowski, S. & Rock, C. O. Regulation of coenzyme A biosynthesis. J. Bacteriol. 148, 926–932 (1981).
Leonardi, R., Zhang, Y. M., Rock, C. O. & Jackowski, S. Coenzyme A: back in action. Prog. Lipid Res. 44, 125–153 (2005).
Robishaw, J. D., Berkich, D. & Neely, J. R. Rate-limiting step and control of coenzyme A synthesis in cardiac muscle. J. Biol. Chem. 257, 10967–10972 (1982).
Li, L. et al. Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): new insights into the biology of hydrogen sulfide. Circulation 117, 2351–2360 (2008).
Yoneshiro, T. et al. BCAA catabolism in brown fat controls energy homeostasis through SLC25A44. Nature 572, 614–619 (2019).
Gietzen, D. W. & Aja, S. M. The brain’s response to an essential amino acid-deficient diet and the circuitous route to a better meal. Mol. Neurobiol. 46, 332–348 (2012).
Fabbiano, S. et al. Caloric restriction leads to browning of white adipose tissue through type 2 immune signaling. Cell Metab. 24, 434–446 (2016).
Horton, J. D., Goldstein, J. L. & Brown, M. S. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest. 109, 1125–1131 (2002).
Go, G. W. & Mani, A. Low-density lipoprotein receptor (LDLR) family orchestrates cholesterol homeostasis. Yale J. Biol. Med. 85, 19–28 (2012).
Horton, J. D., Cohen, J. C. & Hobbs, H. H. Molecular biology of PCSK9: its role in LDL metabolism. Trends Biochem. Sci. 32, 71–77 (2007).
Rouland, A. et al. Role of apolipoprotein C1 in lipoprotein metabolism, atherosclerosis and diabetes: a systematic review. Cardiovasc. Diabetol. 21, 272 (2022).
DeNicola, G. M. et al. NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nat. Genet. 47, 1475–1481 (2015).
He, C. H. et al. Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation. J. Biol. Chem. 276, 20858–20865 (2001).
Kasai, S. et al. Role of the ISR-ATF4 pathway and its cross talk with Nrf2 in mitochondrial quality control. J. Clin. Biochem. Nutr. 64, 1–12 (2019).
Copple, I. M. et al. The hepatotoxic metabolite of acetaminophen directly activates the Keap1-Nrf2 cell defense system. Hepatology 48, 1292–1301 (2008).
Itoh, K. et al. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 13, 76–86 (1999).
Eisenstein, A. et al. Activation of the transcription factor NRF2 mediates the anti-inflammatory properties of a subset of over-the-counter and prescription NSAIDs. Immunity 55, 1082–1095 e1085 (2022).
Patel, S. et al. GDF15 provides an endocrine signal of nutritional stress in mice and humans. Cell Metab. 29, 707–718 (2019).
Qi, L. et al. TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism. Science 312, 1763–1766 (2006).
Asantewaa, G. et al. Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression. Nat. Commun. 15, 6152 (2024).
Naquet, P., Kerr, E. W., Vickers, S. D. & Leonardi, R. Regulation of coenzyme A levels by degradation: the ‘ins and outs’. Prog. Lipid Res. 78, 101028 (2020).
Simcox, J. et al. Global analysis of plasma lipids identifies liver-derived acylcarnitines as a fuel source for brown fat thermogenesis. Cell Metab. 26, 509–522 (2017).
Rahbani, J. F. et al. Creatine kinase B controls futile creatine cycling in thermogenic fat. Nature 590, 480–485 (2021).
Vina, J. et al. The effect of cysteine oxidation on isolated hepatocytes. Biochem. J. 212, 39–44 (1983).
Triguero, A. et al. Liver intracellular l-cysteine concentration is maintained after inhibition of the trans-sulfuration pathway by propargylglycine in rats. Br. J. Nutr. 78, 823–831 (1997).
Stipanuk, M. H., Dominy, J. E. Jr, Lee, J. I. & Coloso, R. M. Mammalian cysteine metabolism: new insights into regulation of cysteine metabolism. J. Nutr. 136, 1652S–1659S (2006).
Bradley, H. et al. Sulfate metabolism is abnormal in patients with rheumatoid arthritis. Confirmation by in vivo biochemical findings. J. Rheumatol. 21, 1192–1196 (1994).
Elshorbagy, A. K., Valdivia-Garcia, M., Refsum, H. & Butte, N. The association of cysteine with obesity, inflammatory cytokines and insulin resistance in Hispanic children and adolescents. PLoS ONE 7, e44166 (2012).
Gordon, C., Bradley, H., Waring, R. H. & Emery, P. Abnormal sulphur oxidation in systemic lupus erythematosus. Lancet 339, 25–26 (1992).
Heafield, M. T. et al. Plasma cysteine and sulphate levels in patients with motor neurone, Parkinson’s and Alzheimer’s disease. Neurosci. Lett. 110, 216–220 (1990).
Ozkan, Y., Ozkan, E. & Simsek, B. Plasma total homocysteine and cysteine levels as cardiovascular risk factors in coronary heart disease. Int. J. Cardiol. 82, 269–277 (2002).
Kiselevsky, Y. V., Ostrovtsova, S. A. & Strumilo, S. A. Kinetic characterization of the pyruvate and oxoglutarate dehydrogenase complexes from human heart. Acta Biochim. Pol. 37, 135–139 (1990).
Marcel, Y. L. & Suzue, G. Kinetic studies on the specificity of long chain acyl coenzyme A synthetase from rat liver microsomes. J. Biol. Chem. 247, 4433–4436 (1972).
Chen, G., Chen, Z., Hu, Y. & Huang, P. Inhibition of mitochondrial respiration and rapid depletion of mitochondrial glutathione by β-phenethyl isothiocyanate: mechanisms for anti-leukemia activity. Antioxid. Redox Signal. 15, 2911–2921 (2011).
Zhang, G. et al. Integrated stress response couples mitochondrial protein translation with oxidative stress control. Circulation 144, 1500–1515 (2021).
Romero, R. et al. Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis. Nat. Med. 23, 1362–1368 (2017).
Mina, A. I. et al. CalR: a web-based analysis tool for indirect calorimetry experiments. Cell Metab. 28, 656–666 (2018).
Anders, S., Pyl, P. T. & Huber, W. HTSeq-a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166–169 (2015).
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
Banh, R. S. et al. The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway. Nature 597, 420–425 (2021).
Chen, W. W., Freinkman, E., Wang, T., Birsoy, K. & Sabatini, D. M. Absolute quantification of matrix metabolites reveals the dynamics of mitochondrial metabolism. Cell 166, 1324–1337 (2016).
Simon-Manso, Y. et al. Metabolite profiling of a NIST Standard Reference Material for human plasma (SRM 1950): GC-MS, LC-MS, NMR, and clinical laboratory analyses, libraries, and web-based resources. Anal. Chem. 85, 11725–11731 (2013).
Smith, C. A. et al. METLIN: a metabolite mass spectral database. Ther. Drug monit. 27, 747–751 (2005).
Virtanen, P. et al. SciPy 1.0: fundamental algorithms for scientific computing in Python. Nat. Methods 17, 261–272 (2020).