1932

Abstract

The original description of dietary methionine restriction (MR) used semipurified diets to limit methionine intake to 20% of normal levels, and this reduction in dietary methionine increased longevity by ∼30% in rats. The MR diet also produces paradoxical increases in energy intake and expenditure and limits fat deposition while reducing tissue and circulating lipids and enhancing overall insulin sensitivity. In the years following the original 1993 report, a comprehensive effort has been made to understand the nutrient sensing and signaling systems linking reduced dietary methionine to the behavioral, physiological, biochemical, and transcriptional components of the response. Recent work has shown that transcriptional activation of hepatic fibroblast growth factor 21 (FGF21) is a key event linking the MR diet to many but not all components of its metabolic phenotype. These findings raise the interesting possibility of developing therapeutic, MR-based diets that produce the beneficial effects of FGF21 by nutritionally modulating its transcription and release.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-nutr-062320-111849
2022-08-22
2024-12-10
Loading full text...

Full text loading...

/deliver/fulltext/nutr/42/1/annurev-nutr-062320-111849.html?itemId=/content/journals/10.1146/annurev-nutr-062320-111849&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Adams AC, Cheng CC, Coskun T, Kharitonenkov A. 2012. FGF21 requires βklotho to act in vivo. PLOS ONE 7:e49977
    [Google Scholar]
  2. 2.
    Adams AC, Coskun T, Rovira AR, Schneider MA, Raches DW et al. 2012. Fundamentals of FGF19 & FGF21 action in vitro and in vivo. PLOS ONE 7:e38438
    [Google Scholar]
  3. 3.
    Anthony TG, Gietzen DW. 2013. Detection of amino acid deprivation in the central nervous system. Curr. Opin. Clin. Nutr. Metab. Care 16:96–101
    [Google Scholar]
  4. 4.
    Anthony TG, McDaniel BJ, Byerley RL, McGrath BC, Cavener DDR et al. 2004. Preservation of liver protein synthesis during dietary leucine deprivation occurs at the expense of skeletal muscle mass in mice deleted for eIF2 kinase GCN2. J. Biol. Chem. 279:36553–61
    [Google Scholar]
  5. 5.
    Anthony TG, Morrison CD, Gettys TW. 2013. Remodeling of lipid metabolism by dietary restriction of essential amino acids. Diabetes 62:2635–44
    [Google Scholar]
  6. 6.
    Anthony TG, Reiter AK, Anthony JC, Kimball SR, Jefferson LS. 2001. Deficiency of dietary EAA preferentially inhibits mRNA translation of ribosomal proteins in liver of meal-fed rats. Am. J. Physiol. Endocrinol. Metab. 281:E430–39
    [Google Scholar]
  7. 7.
    Barzilai N, Banerjee S, Hawkins M, Chen W, Rossetti L 1998. Caloric restriction reverses hepatic insulin resistance in aging rats by decreasing visceral fat. J. Clin. Investig. 101:1353–61
    [Google Scholar]
  8. 8.
    Barzilai N, Ferrucci L. 2012. Insulin resistance and aging: a cause or a protective response?. J. Gerontol. A Biol. Sci. Med. Sci. 67:1329–31
    [Google Scholar]
  9. 9.
    Barzilai N, Gabriely I. 2001. The role of fat depletion in the biological benefits of caloric restriction. J. Nutr. 131:S903–6
    [Google Scholar]
  10. 10.
    Barzilai N, Rossetti L. 1995. Relationship between changes in body composition and insulin responsiveness in models of the aging rat. Am. J. Physiol. Endocrinol. Metab. 269:E591–97
    [Google Scholar]
  11. 11.
    Ben-Sahra I, Howell JJ, Asara JM, Manning BD. 2013. Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. Science 339:1323–28
    [Google Scholar]
  12. 12.
    Berg BN, Simms HS. 1960. Nutrition and longevity in the rat. II. Longevity and onset of disease with different levels of food intake. J. Nutr. 71:255–63
    [Google Scholar]
  13. 13.
    Berry SA, Brown CS, Greene C, Camp KM, McDonough S et al. 2020. Medical foods for inborn errors of metabolism: history, current status, and critical need. Pediatrics 145:e20192261
    [Google Scholar]
  14. 14.
    BonDurant LD, Ameka M, Naber MC, Markan KR, Idiga SO et al. 2017. FGF21 regulates metabolism through adipose-dependent and -independent mechanisms. Cell Metab. 25:935–44.e4
    [Google Scholar]
  15. 15.
    Bookout AL, de Groot MH, Owen BM, Lee S, Gautron L et al. 2013. FGF21 regulates metabolism and circadian behavior by acting on the nervous system. Nat. Med. 19:1147–52
    [Google Scholar]
  16. 16.
    Carpenter KJ. 1997. Some amino acids are indispensable for growth (Osborne and Mendel, 1914–1916). J. Nutr. 127:S1031–32
    [Google Scholar]
  17. 17.
    Carpenter KJ. 2003. A short history of nutritional science: part 1 (1785–1885). J. Nutr. 133:638–45
    [Google Scholar]
  18. 18.
    Carpenter KJ. 2003. A short history of nutritional science: part 2 (1885–1912). J. Nutr. 133:975–84
    [Google Scholar]
  19. 19.
    Carpenter KJ. 2003. A short history of nutritional science: part 3 (1912–1944). J. Nutr. 133:3023–32
    [Google Scholar]
  20. 20.
    Charles ED, Neuschwander-Tetri BA, Pablo Frias J, Kundu S, Luo Y et al. 2019. Pegbelfermin (BMS-986036), PEGylated FGF21, in patients with obesity and type 2 diabetes: results from a randomized phase 2 study. Obesity 27:41–49
    [Google Scholar]
  21. 21.
    Chen H, Pan YX, Dudenhausen EE, Kilberg MS. 2004. Amino acid deprivation induces the transcription rate of the human asparagine synthetase gene through a timed program of expression and promoter binding of nutrient-responsive basic region/leucine zipper transcription factors as well as localized histone acetylation. J. Biol. Chem. 279:50829–39
    [Google Scholar]
  22. 22.
    Cheng Y, Meng Q, Wang C, Li H, Huang Z et al. 2010. Leucine deprivation decreases fat mass by stimulation of lipolysis in white adipose tissue and upregulation of uncoupling protein 1 (UCP1) in brown adipose tissue. Diabetes 59:17–25
    [Google Scholar]
  23. 23.
    Cheng Y, Zhang Q, Meng Q, Xia T, Huang Z et al. 2011. Leucine deprivation stimulates fat loss via increasing CRH expression in the hypothalamus and activating the sympathetic nervous system. Mol. Endocrinol. 25:1624–35
    [Google Scholar]
  24. 24.
    Coskun T, Bina HA, Schneider MA, Dunbar JD, Hu CC et al. 2008. Fibroblast growth factor 21 corrects obesity in mice. Endocrinology 149:6018–27
    [Google Scholar]
  25. 25.
    Cullinan SB, Diehl JA. 2004. PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress. J. Biol. Chem. 279:20108–17
    [Google Scholar]
  26. 26.
    De Sousa–Coelho AL, Marrero PF, Haro D 2012. Activating transcription factor 4–dependent induction of FGF21 during amino acid deprivation. Biochem. J. 443:165–71
    [Google Scholar]
  27. 27.
    Deval C, Chaveroux C, Maurin AC, Cherasse Y, Parry L et al. 2009. Amino acid limitation regulates the expression of genes involved in several specific biological processes through GCN2-dependent and GCN2-independent pathways. FEBS J. 276:707–18
    [Google Scholar]
  28. 28.
    Ding X, Boney-Montoya J, Owen BM, Bookout AL, Coate KC et al. 2012. βKlotho is required for fibroblast growth factor 21 effects on growth and metabolism. Cell Metab. 16:387–93
    [Google Scholar]
  29. 29.
    Donnelly N, Gorman AM, Gupta S, Samali A. 2013. The eIF2α kinases: their structures and functions. Cell. Mol. Life Sci. 70:3493–511
    [Google Scholar]
  30. 30.
    Douris N, Stevanovic DM, Fisher FM, Cisu TI, Chee MJ et al. 2015. Central fibroblast growth factor 21 browns white fat via sympathetic action in male mice. Endocrinology 156:2470–81
    [Google Scholar]
  31. 31.
    Elia M, Livesey G. 1988. Theory and validity of indirect calorimetry during net lipid synthesis. Am. J. Clin. Nutr. 47:591–607
    [Google Scholar]
  32. 32.
    Elshorbagy AK, Valdivia-Garcia M, Mattocks DA, Plummer JD, Orentreich DS et al. 2013. Effect of taurine and N-acetylcysteine on methionine restriction–mediated adiposity resistance. Metabolism 62:509–17
    [Google Scholar]
  33. 33.
    Elshorbagy AK, Valdivia-Garcia M, Mattocks DA, Plummer JD, Smith AD et al. 2011. Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase. J. Lipid Res. 52:104–12
    [Google Scholar]
  34. 34.
    Erickson A, Moreau R. 2016. The regulation of FGF21 gene expression by metabolic factors and nutrients. Horm. Mol. Biol. Clin. Investig. 30:20160016
    [Google Scholar]
  35. 35.
    Fang H, Stone KP, Forney LA, Sims LC, Gutierrez GC et al. 2021. Implementation of dietary methionine restriction using casein after selective, oxidative deletion of methionine. iScience 24:102470
    [Google Scholar]
  36. 36.
    Fang H, Stone KP, Ghosh S, Forney LA, Gettys TW. 2021. The role of reduced methionine in mediating the metabolic responses to protein restriction using different sources of protein. Nutrients 13:2609
    [Google Scholar]
  37. 37.
    Fang H, Stone KP, Ghosh S, Forney LA, Sims LC et al. 2021. Hepatic Nfe2l2 is not an essential mediator of the metabolic phenotype produced by dietary methionine restriction. Nutrients 13:18
    [Google Scholar]
  38. 38.
    Ferrannini E. 1988. The theoretical bases of indirect calorimetry: a review. Metabolism 37:287–301
    [Google Scholar]
  39. 39.
    Finkelstein JD, Martin JJ, Harris BJ. 1988. Methionine metabolism in mammals. The methionine-sparing effect of cystine. J. Biol. Chem. 263:11750–54
    [Google Scholar]
  40. 40.
    Forney LA, Fang H, Sims LC, Stone KP, Vincik LY et al. 2020. Dietary methionine restriction signals to the brain through fibroblast growth factor 21 to regulate energy balance and remodeling of adipose tissue. Obesity 28:1912–21
    [Google Scholar]
  41. 41.
    Forney LA, Stone KP, Gibson AN, Vick AM, Sims LC et al. 2020. Sexually dimorphic effects of dietary methionine restriction are dependent on age when the diet is introduced. Obesity 28:581–89
    [Google Scholar]
  42. 42.
    Forney LA, Wanders D, Stone KP, Pierse A, Gettys TW. 2017. Concentration-dependent linkage of dietary methionine restriction to the components of its metabolic phenotype. Obesity 25:730–38
    [Google Scholar]
  43. 43.
    Furusawa Y, Uruno A, Yagishita Y, Higashi C, Yamamoto M. 2014. Nrf2 induces fibroblast growth factor 21 in diabetic mice. Genes Cells 19:864–78
    [Google Scholar]
  44. 44.
    Gabriely I, Ma XH, Yang XM, Atzmon G, Rajala MW et al. 2002. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process?. Diabetes 51:2951–58
    [Google Scholar]
  45. 45.
    Gaich G, Chien JY, Fu H, Glass LC, Deeg MA et al. 2013. The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metab. 18:333–40
    [Google Scholar]
  46. 46.
    Geller S, Arribat Y, Netzahualcoyotzi C, Lagarrigue S, Carneiro L et al. 2019. Tanycytes regulate lipid homeostasis by sensing free fatty acids and signaling to key hypothalamic neuronal populations via FGF21 secretion. Cell Metab. 30:833–44.e7
    [Google Scholar]
  47. 47.
    Ghosh S, Forney LA, Wanders D, Stone KP, Gettys TW. 2017. An integrative analysis of tissue-specific transcriptomic and metabolomic responses to short-term dietary methionine restriction in mice. PLOS ONE 12:e0177513
    [Google Scholar]
  48. 48.
    Ghosh S, Wanders D, Stone KP, Van NT, Cortez CC, Gettys TW. 2014. A systems biology analysis of the unique and overlapping transcriptional responses to caloric restriction and dietary methionine restriction in rats. FASEB J. 28:2577–90
    [Google Scholar]
  49. 49.
    Gietzen DW, Aja SM. 2012. The brain's response to an essential amino acid–deficient diet and the circuitous route to a better meal. Mol. Neurobiol. 46:332–48
    [Google Scholar]
  50. 50.
    Grandison RC, Piper MD, Partridge L. 2009. Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature 462:1061–64
    [Google Scholar]
  51. 51.
    Guo F, Cavener DR. 2007. The GCN2 eIF2α kinase regulates fatty-acid homeostasis in the liver during deprivation of an essential amino acid. Cell Metab. 5:103–14
    [Google Scholar]
  52. 52.
    Hao S, Sharp JW, Ross-Inta CM, McDaniel BJ, Anthony TG et al. 2005. Uncharged tRNA and sensing of amino acid deficiency in mammalian piriform cortex. Science 307:1776–78
    [Google Scholar]
  53. 53.
    Harding HP, Novoa I, Zhang Y, Zeng H, Wek R et al. 2000. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol. Cell 6:1099–108
    [Google Scholar]
  54. 54.
    Harding HP, Zhang Y, Zeng H, Novoa I, Lu PD et al. 2003. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol. Cell 11:619–33
    [Google Scholar]
  55. 55.
    Hasek BE, Boudreau A, Shin J, Feng D, Hulver M et al. 2013. Remodeling the integration of lipid metabolism between liver and adipose tissue by dietary methionine restriction in rats. Diabetes 62:3362–72
    [Google Scholar]
  56. 56.
    Hasek BE, Stewart LK, Henagan TM, Boudreau A, Lenard NR et al. 2010. Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states. Am. J. Physiol. Regul. Integr. Comp. Physiol. 299:R728–39
    [Google Scholar]
  57. 57.
    Hayes JD, Dinkova-Kostova AT. 2014. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem. Sci. 39:199–218
    [Google Scholar]
  58. 58.
    Henriques V, Hansen C. 1905. Ober eiweißsynthese im tierkörper. Hoppe Seylers Z. Physiol. Chem. 43:417–46
    [Google Scholar]
  59. 59.
    Holland WL, Adams AC, Brozinick JT, Bui HH, Miyauchi Y et al. 2013. An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice. Cell Metab. 17:790–97
    [Google Scholar]
  60. 60.
    Hopkins FG, Cole SW. 1902. A preliminary study of a hitherto undescribed product of tryptic digestion. J. Physiol. 27:418–28
    [Google Scholar]
  61. 61.
    Huffman DM, Barzilai N. 2009. Role of visceral adipose tissue in aging. Biochim. Biophys. Acta 1790:1117–23
    [Google Scholar]
  62. 62.
    Huffman DM, Barzilai N. 2010. Contribution of adipose tissue to health span and longevity. Interdiscip. Top. Gerontol. 37:1–19
    [Google Scholar]
  63. 63.
    Hultman K, Scarlett JM, Baquero AF, Cornea A, Zhang Y et al. 2019. The central fibroblast growth factor receptor/beta klotho system: comprehensive mapping in Mus musculus and comparisons to nonhuman primate and human samples using an automated in situ hybridization platform. J. Comp. Neurol. 527:2069–85
    [Google Scholar]
  64. 64.
    Jensen-Cody SO, Flippo KH, Claflin KE, Yavuz Y, Sapouckey SA et al. 2020. FGF21 signals to glutamatergic neurons in the ventromedial hypothalamus to suppress carbohydrate intake. Cell Metab. 32:273–86.e6
    [Google Scholar]
  65. 65.
    Jonsson WO, Margolies NS, Mirek ET, Zhang Q, Linden MA et al. 2021. Physiologic responses to dietary sulfur amino acid restriction in mice are influenced by Atf4 status and biological sex. J. Nutr. 151:785–99
    [Google Scholar]
  66. 66.
    Kelley DE, Mandarino LJ 2000. Fuel selection in human skeletal muscle in insulin resistance: a reexamination. Diabetes 49:677–83
    [Google Scholar]
  67. 67.
    Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R et al. 2005. FGF-21 as a novel metabolic regulator. J. Clin. Investig. 115:1627–35
    [Google Scholar]
  68. 68.
    Kharitonenkov A, Wroblewski VJ, Koester A, Chen YF, Clutinger CK et al. 2007. The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. Endocrinology 148:774–81
    [Google Scholar]
  69. 69.
    Kilberg MS, Shan J, Su N. 2009. ATF4-dependent transcription mediates signaling of amino acid limitation. Trends Endocrinol. Metab. 20:436–43
    [Google Scholar]
  70. 70.
    Kimball S, Anthony TG, Cavener D, Jefferson LS. 2004. Nutrient signaling through mammalian GCN2. Top. Curr. Genet. 7:113–30
    [Google Scholar]
  71. 71.
    Lee J, Ozcan U. 2014. Unfolded protein response signaling and metabolic diseases. J. Biol. Chem. 289:1203–11
    [Google Scholar]
  72. 72.
    Lees EK, Banks R, Cook C, Hill S, Morrice N et al. 2017. Direct comparison of methionine restriction with leucine restriction on the metabolic health of C57BL/6J mice. Sci. Rep. 7:9977
    [Google Scholar]
  73. 73.
    Mair W, Dillin A. 2008. Aging and survival: the genetics of life span extension by dietary restriction. Annu. Rev. Biochem. 77:727–54
    [Google Scholar]
  74. 74.
    Mair W, Piper MD, Partridge L. 2005. Calories do not explain extension of life span by dietary restriction in Drosophila. PLOS Biol. 3:e223
    [Google Scholar]
  75. 75.
    Malloy VL, Krajcik RA, Bailey SJ, Hristopoulos G, Plummer JD, Orentreich N. 2006. Methionine restriction decreases visceral fat mass and preserves insulin action in aging male Fischer 344 rats independent of energy restriction. Aging Cell 5:305–14
    [Google Scholar]
  76. 76.
    Maurin AC, Jousse C, Averous J, Parry L, Bruhat A et al. 2005. The GCN2 kinase biases feeding behavior to maintain amino acid homeostasis in omnivores. Cell Metab. 1:273–77
    [Google Scholar]
  77. 77.
    McCay CM, Crowell MF, Maynard LA. 1935. The effect of retarded growth upon the length of life span and upon the ultimate body size. J. Nutr. 10:63–79
    [Google Scholar]
  78. 78.
    McCollum EV. 1953. My early experiences in the study of foods and nutrition. Annu. Rev. Biochem. 22:1–16
    [Google Scholar]
  79. 79.
    McCollum EV. 1957. A History of Nutrition. The Sequence of Ideas in Nutrition Investigations Boston, MA: Houghton Mifflin
    [Google Scholar]
  80. 80.
    Miller RA, Buehner G, Chang Y, Harper JM, Sigler R, Smith-Wheelock M. 2005. 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 4:119–25
    [Google Scholar]
  81. 81.
    Mirzaei H, Suarez JA, Longo VD. 2014. Protein and amino acid restriction, aging and disease: from yeast to humans. Trends Endocrinol. Metab. 25:558–66
    [Google Scholar]
  82. 82.
    (US) Natl. Res. Counc. Subcomm. Lab. Anim. Nutr 1995. Nutrient Requirements of Laboratory Animals Washington, DC: Natl. Acad. Sci. 173 pp .
    [Google Scholar]
  83. 83.
    Orentreich N, Matias JR, DeFelice A, Zimmerman JA. 1993. Low methionine ingestion by rats extends life span. J. Nutr. 123:269–74
    [Google Scholar]
  84. 84.
    Osborne TB, Ferry LB, Ferry EL, Wakeman AJ. 1914. Amino-acids in nutrition and growth. J. Biol. Chem. 17:325–49
    [Google Scholar]
  85. 85.
    Osborne TB, Mendel LB. 1916. A quantitative comparison of casein, lactalbumin, and edestin for growth or maintenance. J. Biol. Chem. 26:1–23
    [Google Scholar]
  86. 86.
    Osborne TB, Mendel LB, Ferry EL, Wakeman AJ. 1916. The amino-acid minimum for maintenance and growth, as exemplified by further experiments with lysine and tryptophane. J. Biol. Chem. 25:1–12
    [Google Scholar]
  87. 87.
    Osborne TB, Mendel LB, Ferry EL, Wakeman AJ. 1916. The effect of the amino-acid content of the diet on the growth of chickens. J. Biol. Chem. 26:293–300
    [Google Scholar]
  88. 88.
    Owen BM, Ding X, Morgan DA, Coate KC, Bookout AL et al. 2014. FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss. Cell Metab. 20:670–77
    [Google Scholar]
  89. 89.
    Owen BM, Mangelsdorf DJ, Kliewer SA. 2015. Tissue-specific actions of the metabolic hormones FGF15/19 and FGF21. Trends Endocrinol. Metab. 26:22–29
    [Google Scholar]
  90. 90.
    Pakos-Zebrucka K, Koryga I, Mnich K, Ljujic M, Samali A, Gorman AM. 2016. The integrated stress response. EMBO Rep. 17:1374–95
    [Google Scholar]
  91. 91.
    Palam LR, Baird TD, Wek RC. 2011. Phosphorylation of eIF2 facilitates ribosomal bypass of an inhibitory upstream ORF to enhance CHOP translation. J. Biol. Chem. 286:10939–49
    [Google Scholar]
  92. 92.
    Palii SS, Kays CE, Deval C, Bruhat A, Fafournoux P, Kilberg MS. 2009. Specificity of amino acid regulated gene expression: analysis of genes subjected to either complete or single amino acid deprivation. Amino Acids 37:79–88
    [Google Scholar]
  93. 93.
    Pan YX, Chen H, Siu F, Kilberg MS. 2003. Amino acid deprivation and endoplasmic reticulum stress induce expression of multiple activating transcription factor-3 mRNA species that, when overexpressed in HepG2 cells, modulate transcription by the human asparagine synthetase promoter. J. Biol. Chem. 278:38402–12
    [Google Scholar]
  94. 94.
    Pan YX, Chen H, Thiaville MM, Kilberg MS. 2007. Activation of the ATF3 gene through a co-ordinated amino acid–sensing response programme that controls transcriptional regulation of responsive genes following amino acid limitation. Biochem. J. 401:299–307
    [Google Scholar]
  95. 95.
    Park Y, Reyna-Neyra A, Philippe L, Thoreen CC 2017. mTORC1 balances cellular amino acid supply with demand for protein synthesis through post-transcriptional control of ATF4. Cell Rep. 19:1083–90
    [Google Scholar]
  96. 96.
    Patil YN, Dille KN, Burk DH, Cortez CC, Gettys TW. 2015. Cellular and molecular remodeling of inguinal adipose tissue mitochondria by dietary methionine restriction. J. Nutr. Biochem. 26:1235–47
    [Google Scholar]
  97. 97.
    Perrone CE, Mattocks DA, Hristopoulos G, Plummer JD, Krajcik RA, Orentreich N. 2008. Methionine restriction effects on 11β-HSD1 activity and lipogenic/lipolytic balance in F344 rat adipose tissue. J. Lipid Res. 49:12–23
    [Google Scholar]
  98. 98.
    Perrone CE, Mattocks DA, Jarvis-Morar M, Plummer JD, Orentreich N. 2010. Methionine restriction effects on mitochondrial biogenesis and aerobic capacity in white adipose tissue, liver, and skeletal muscle of F344 rats. Metabolism 59:1000–11
    [Google Scholar]
  99. 99.
    Perrone CE, Mattocks DA, Plummer JD, Chittur SV, Mohney R et al. 2012. Genomic and metabolic responses to methionine-restricted and methionine-restricted, cysteine-supplemented diets in Fischer 344 rat inguinal adipose tissue, liver and quadriceps muscle. J. Nutrigenet. Nutrigenom. 5:132–57
    [Google Scholar]
  100. 100.
    Pettit AP, Jonsson WO, Bargoud AR, Mirek ET, Peelor FF 3rd et al. 2017. Dietary methionine restriction regulates liver protein synthesis and gene expression independently of eukaryotic initiation factor 2 phosphorylation in mice. J. Nutr. 147:1031–40
    [Google Scholar]
  101. 101.
    Piper MD, Partridge L, Raubenheimer D, Simpson SJ. 2011. Dietary restriction and aging: a unifying perspective. Cell Metab. 14:154–60
    [Google Scholar]
  102. 102.
    Plaisance EP, Greenway FL, Boudreau A, Hill KL, Johnson WD et al. 2011. Dietary methionine restriction increases fat oxidation in obese adults with metabolic syndrome. J. Clin. Endocrinol. Metab. 96:E836–40
    [Google Scholar]
  103. 103.
    Plaisance EP, Henagan TM, Echlin H, Boudreau A, Hill KL et al. 2010. Role of β-adrenergic receptors in the hyperphagic and hypermetabolic responses to dietary methionine restriction. Am. J. Physiol. Regul. Integr. Comp. Physiol. 299:R740–50
    [Google Scholar]
  104. 104.
    Richie JP Jr., Leutzinger Y, Parthasarathy S, Malloy V, Orentreich N, Zimmerman JA. 1994. Methionine restriction increases blood glutathione and longevity in F344 rats. FASEB J. 8:1302–7
    [Google Scholar]
  105. 105.
    Rose WC, Oesterling MJ, Womack M. 1948. Comparative growth on diets containing ten and 19 amino acids, with further observations upon the role of glutamic and aspartic acids. J. Biol. Chem. 176:753–62
    [Google Scholar]
  106. 106.
    Santoso P, Nakata M, Shiizaki K, Boyang Z, Parmila K et al. 2017. Fibroblast growth factor 21, assisted by elevated glucose, activates paraventricular nucleus NUCB2/Nesfatin-1 neurons to produce satiety under fed states. Sci. Rep. 7:45819
    [Google Scholar]
  107. 107.
    Sanyal A, Charles ED, Neuschwander-Tetri BA, Loomba R, Harrison SA et al. 2019. Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial. Lancet 392:2705–17
    [Google Scholar]
  108. 108.
    Schlein C, Talukdar S, Heine M, Fischer AW, Krott LM et al. 2016. FGF21 lowers plasma triglycerides by accelerating lipoprotein catabolism in white and brown adipose tissues. Cell Metab. 23:441–53
    [Google Scholar]
  109. 109.
    Seo J, Fortuno ES 3rd, Suh JM, Stenesen D, Tang W et al. 2009. Atf4 regulates obesity, glucose homeostasis, and energy expenditure. Diabetes 58:2565–73
    [Google Scholar]
  110. 110.
    Shan JX, Ord D, Ord T, Kilberg MS. 2009. Elevated ATF4 expression, in the absence of other signals, is sufficient for transcriptional induction via CCAAT enhancer–binding protein–activating transcription factor response elements. J. Biol. Chem. 284:21241–48
    [Google Scholar]
  111. 111.
    Sharma S, Dixon T, Jung S, Graff EC, Forney LA et al. 2019. Dietary methionine restriction reduces inflammation independent of FGF21 action. Obesity 27:1305–13
    [Google Scholar]
  112. 112.
    Solon-Biet SM, Cogger VC, Pulpitel T, Heblinski M, Wahl D et al. 2016. Defining the nutritional and metabolic context of FGF21 using the geometric framework. Cell Metab. 24:555–65
    [Google Scholar]
  113. 113.
    Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE et al. 2014. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum–fed mice. Cell Metab. 19:418–30
    [Google Scholar]
  114. 114.
    Song P, Zechner C, Hernandez G, Canovas J, Xie Y et al. 2018. The hormone FGF21 stimulates water drinking in response to ketogenic diet and alcohol. Cell Metab. 27:1338–47.e4
    [Google Scholar]
  115. 115.
    Sood R, Porter AC, Olsen DA, Cavener DR, Wek RC. 2000. A mammalian homologue of GCN2 protein kinase important for translational control by phosphorylation of eukaryotic initiation factor-2α. Genetics 154:787–801
    [Google Scholar]
  116. 116.
    Stone KP, Ghosh S, Kovalik JP, Orgeron M, Wanders D et al. 2021. The acute transcriptional responses to dietary methionine restriction are triggered by inhibition of ternary complex formation and linked to Erk1/2, mTOR, and ATF4. Sci. Rep. 11:3765
    [Google Scholar]
  117. 117.
    Stone KP, Wanders D, Calderon LF, Spurgin SB, Scherer PE, Gettys TW. 2015. Compromised responses to dietary methionine restriction in adipose tissue but not liver of ob/ob mice. Obesity 23:1836–44
    [Google Scholar]
  118. 118.
    Stone KP, Wanders D, Orgeron M, Cortez CC, Gettys TW. 2014. Mechanisms of increased in vivo insulin sensitivity by dietary methionine restriction in mice. Diabetes 63:3721–33
    [Google Scholar]
  119. 119.
    Su N, Kilberg MS. 2008. C/EBP homology protein (CHOP) interacts with activating transcription factor 4 (ATF4) and negatively regulates the stress-dependent induction of the asparagine synthetase gene. J. Biol. Chem. 283:35106–17
    [Google Scholar]
  120. 120.
    Sun L, Sadighi Akha AA, Miller RA, Harper JM. 2009. Life-span extension in mice by preweaning food restriction and by methionine restriction in middle age. J. Gerontol. A Biol. Sci. Med. Sci. 64:711–22
    [Google Scholar]
  121. 121.
    Talukdar S, Zhou Y, Li D, Rossulek M, Dong J et al. 2016. A long-acting FGF21 molecule, PF-05231023, decreases body weight and improves lipid profile in non-human primates and type 2 diabetic subjects. Cell Metab. 23:427–40
    [Google Scholar]
  122. 122.
    Turner T, Chen X, Zahner M, Opsahl A, DeMarco G et al. 2018. FGF21 increases water intake, urine output and blood pressure in rats. PLOS ONE 13:e0202182
    [Google Scholar]
  123. 123.
    Vickery HB, Schmidt CLA. 1931. The history of the discovery of the amino acids. Chem. Rev. 9:169–318
    [Google Scholar]
  124. 124.
    Visweswaraiah J, Lageix S, Castilho BA, Izotova L, Kinzy TG et al. 2011. Evidence that eukaryotic translation elongation factor 1A (eEF1A) binds the Gcn2 protein C terminus and inhibits Gcn2 activity. J. Biol. Chem. 286:36568–79
    [Google Scholar]
  125. 125.
    Wanders D, Burk DH, Cortez CC, Tan NT, Stone KP et al. 2015. UCP1 is an essential mediator of the effects of methionine restriction on energy balance but not insulin sensitivity. FASEB J. 29:2603–15
    [Google Scholar]
  126. 126.
    Wanders D, Forney LA, Stone KP, Burk DH, Pierse A, Gettys TW. 2017. FGF21 mediates the thermogenic and insulin-sensitizing effects of dietary methionine restriction but not its effects on hepatic lipid metabolism. Diabetes 66:858–67
    [Google Scholar]
  127. 127.
    Wanders D, Forney LA, Stone KP, Hasek BE, Johnson WD, Gettys TW. 2018. The components of age-dependent effects of dietary methionine restriction on energy balance in rats. Obesity 26:740–46
    [Google Scholar]
  128. 128.
    Wanders D, Ghosh S, Stone KP, Van NT, Gettys TW 2014. Transcriptional impact of dietary methionine restriction on systemic inflammation: relevance to biomarkers of metabolic disease during aging. Biofactors 40:13–26
    [Google Scholar]
  129. 129.
    Wanders D, Stone KP, Dille K, Simon J, Pierse A, Gettys TW. 2015. Metabolic responses to dietary leucine restriction involve remodeling of adipose tissue and enhanced hepatic insulin signaling. Biofactors 41:391–402
    [Google Scholar]
  130. 130.
    Wanders D, Stone KP, Forney LA, Cortez CC, Dille KN et al. 2016. Role of GCN2-independent signaling through a non-canonical PERK/NRF2 pathway in the physiological responses to dietary methionine restriction. Diabetes 65:1499–510
    [Google Scholar]
  131. 131.
    Wang C, Huang Z, Du Y, Cheng Y, Chen S, Guo F 2010. ATF4 regulates lipid metabolism and thermogenesis. Cell Res. 20:174–84
    [Google Scholar]
  132. 132.
    Xia T, Cheng Y, Zhang Q, Xiao F, Liu B et al. 2012. S6K1 in the central nervous system regulates energy expenditure via MC4R/CRH pathways in response to deprivation of an essential amino acid. Diabetes 61:2461–71
    [Google Scholar]
  133. 133.
    Xu J, Lloyd DJ, Hale C, Stanislaus S, Chen M et al. 2009. Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes 58:250–59
    [Google Scholar]
  134. 134.
    Xu J, Stanislaus S, Chinookoswong N, Lau YY, Hager T et al. 2009. Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulin-resistant mouse models-association with liver and adipose tissue effects. Am. J. Physiol. Endocrinol. Metab. 297:E1105–14
    [Google Scholar]
  135. 135.
    Yoshizawa T, Hinoi E, Jung DY, Kajimura D, Ferron M et al. 2009. The transcription factor ATF4 regulates glucose metabolism in mice through its expression in osteoblasts. J. Clin. Investig. 119:2807–17
    [Google Scholar]
  136. 136.
    Zhang P, McGrath BC, Reinert J, Olsen DS, Lei L et al. 2002. The GCN2 eIF2α kinase is required for adaptation to amino acid deprivation in mice. Mol. Cell. Biol. 22:6681–88
    [Google Scholar]
  137. 137.
    Zimmerman JA, Malloy V, Krajcik R, Orentreich N. 2003. Nutritional control of aging. Exp. Gerontol. 38:47–52
    [Google Scholar]
/content/journals/10.1146/annurev-nutr-062320-111849
Loading
/content/journals/10.1146/annurev-nutr-062320-111849
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error