Determinants of GH resistance in malnutrition

Journal of Endocrinology

Volumn 220, Issue 3, 2014, Pages

  Fazeli, Pouneh K ^a   Klibanski, Anne ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Growth hormone; IGF; Neuroendocrinology; Pituitary

Indexed keywords

GROWTH HORMONE; IGF; NEUROENDOCRINOLOGY; PITUITARY;

ANOREXIA NERVOSA; FIBROBLAST GROWTH FACTORS; HUMAN GROWTH HORMONE; HUMANS; INSULIN-LIKE GROWTH FACTOR I; MALNUTRITION;

EID: 84894319630     PISSN: 00220795     EISSN: 14796805     Source Type: Journal    
DOI: 10.1530/JOE-13-0477     Document Type: Review

References (80)

1. American Psychiatric Association 1994 Diagnostic and statisticalmanual of mental disorders (DSM-IV), 4th edn.
2. Washington, DC. Baxter RC & Turtle JR 1978 Regulation of hepatic growth hormone receptors by insulin. Biochemical and Biophysical Research Communications 84 350-357. (doi:10.1016/0006-291X(78)90177-8)
3. Baxter RC, Bryson JM & Turtle JR 1981 The effect of fasting on liver receptors for prolactin and growth hormone. Metabolism 30 1086-1090. (doi:10.1016/0026-0495(81)90052-4)
4. Brick DJ, Gerweck AV, Meenaghan E, Lawson EA, Misra M, Fazeli P, Johnson W, Klibanski A & Miller KK 2010 Determinants of IGF1 and GH across the weight spectrum: from anorexia nervosa to obesity. European Journal of Endocrinology 163 185-191. (doi:10.1530/ EJE-10-0365)
5. ChanJL,WilliamsCJ,Raciti P, BlakemanJ, KelesidisT,Kelesidis I, JohnsonML, Thorner MO & Mantzoros CS 2008 Leptin does not mediate short-term fasting-induced changes in growth hormone pulsatility but increases IGF-I in leptin deficiency states. Journal of Clinical Endocrinology and Metabolism 93 2819-2827. (doi:10.1210/jc.2008-0056)
6. Counts DR, Gwirtsman H, Carlsson LM, Lesem M & Cutler GB Jr 1992 The effect of anorexia nervosa and refeeding on growth hormone-binding protein, the insulin-like growth factors (IGFs), and the IGF-binding proteins. Journal of Clinical Endocrinology and Metabolism 75 762-767. (doi:10.1210/jc.75.3.762)
7. Devine A, Rosen C, Mohan S, Baylink D & Prince RL 1998 Effects of zinc and other nutritional factors on insulin-like growth factor I and insulin-like growth factor binding proteins in postmenopausal women. American Journal of Clinical Nutrition 68 200-206.
8. Dorup I, Flyvbjerg A, Everts ME & Clausen T 1991 Role of insulin-like growth factor-1 and growth hormone in growth inhibition induced by magnesium and zinc deficiencies. British Journal of Nutrition 66 505-521. (doi:10.1079/BJN19910051)
9. Fazeli PK, Lawson EA, Prabhakaran R,Miller KK, Donoho DA, Clemmons DR, Herzog DB, Misra M & Klibanski A 2010a Effects of recombinant human growth hormone in anorexia nervosa: a randomized, placebocontrolled study. Journal of Clinical Endocrinology and Metabolism 95 4889-4897. (doi:10.1210/jc.2010-0493)
10. Fazeli PK, Misra M, Goldstein M, Miller KK & Klibanski A 2010b Fibroblast growth factor-21 may mediate growth hormone resistance in anorexia nervosa. Journal of Clinical Endocrinology and Metabolism 95 369-374. (doi:10.1210/jc.2009-1730)
11. Fichter MM, Pirke KM & Holsboer F 1986 Weight loss causes neuroendocrine disturbances: experimental study in healthy starving subjects. Psychiatry Research 17 61-72. (doi:10.1016/0165-1781(86)90042-9)
12. Flyvbjerg A, Dorup I, Everts ME & Orskov H 1991 Evidence that potassium deficiency induces growth retardation through reduced circulating levels of growth hormone and insulin-like growth factor I. Metabolism 40 769-775. (doi:10.1016/0026-0495(91)90001-D)
13. Frederich RC, Lollmann B, Hamann A, Napolitano-Rosen A, Kahn BB, Lowell BB & Flier JS 1995 Expression of ob mRNA and its encoded protein in rodents. Impact of nutrition and obesity. Journal of Clinical Investigation 96 1658-1663. (doi:10.1172/JCI118206)
14. Frystyk J, Brick DJ, Gerweck AV, Utz AL &Miller KK 2009 Bioactive insulinlike growth factor-I in obesity. Journal of Clinical Endocrinology and Metabolism 94 3093-3097. (doi:10.1210/jc.2009-0614)
15. Gahete MD, Cordoba-Chacon J, Luque RM & Kineman RD 2013 The rise in growth hormone during starvation does not serve to maintain glucose levels or lean mass but is required for appropriate adipose tissue response in female mice. Endocrinology 154 263-269. (doi:10.1210/ en.2012-1849)
16. Gaich G, Chien JY, Fu H, Glass LC, DeegMA, HollandWL, Kharitonenkov A, Bumol T, Schilske HK & Moller DE 2013 The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metabolism 18 333-340. (doi:10.1016/j.cmet.2013.08.005)
17. Galman C, Lundasen T, Kharitonenkov A, Bina HA, ErikssonM, Hafstrom I, Dahlin M, Amark P, Angelin B & Rudling M 2008 The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARa activation in man. Cell Metabolism 8 169-174. (doi:10.1016/j.cmet. 2008.06.014)
18. Gannon MC & Nuttall FQ 2011 Effect of a high-protein diet on ghrelin, growth hormone, and insulin-like growth factor-I and binding proteins 1 and 3 in subjects with type 2 diabetes mellitus. Metabolism 60 1300-1311. (doi:10.1016/j.metabol.2011.01.016)
19. Garfinkel PE, Brown GM, Stancer HC & Moldofsky H 1975 Hypothalamic- pituitary function in anorexia nervosa. Archives of General Psychiatry 32 739-744. (doi:10.1001/archpsyc.1975.01760240067005)
20. Gianotti L, Pincelli AI, Scacchi M, Rolla M, Bellitti D, Arvat E, Lanfranco F, Torsello A, Ghigo E, Cavagnini F et al. 2000 Effects of recombinant human insulin-like growth factor I administration on spontaneous and growth hormone (GH)-releasing hormone-stimulated GH secretion in anorexia nervosa. Journal of Clinical Endocrinology and Metabolism 85 2805-2809. (doi:10.1210/jc.85.8.2805)
21. Gillum MP, Erion DM, Shulman GI 2010 Sirtuin-1 regulation of mammalian metabolism. Trends in Molecular Medicine 17 8-13. (doi:10.1016/j.molmed.2010.09.005)
22. Grinspoon SK, Baum HB, Peterson S & Klibanski A 1995 Effects of rhIGF-I administration on bone turnover during short-term fasting. Journal of Clinical Investigation 96 900-906. (doi:10.1172/JCI118137)
23. Grottoli S, Gasco V,Mainolfi A, Beccuti G, Corneli G, AimarettiG,Dieguez C, Casanueva F & Ghigo E 2008 Growth hormone/insulin-like growth factor I axis, glucose metabolism, and lypolisis but not leptin show some degree of refractoriness to short-term fasting in acromegaly. Journal of Endocrinological Investigation 31 1103-1109.
24. Hartman ML, Clayton PE, Johnson ML, Celniker A, Perlman AJ, Alberti KG, Thorner MO 1993 A low dose euglycemic infusion of recombinant human insulin-like growth factor I rapidly suppresses fasting-enhanced pulsatile growth hormone secretion in humans. Journal of Clinical Investigation 91 2453-2462. (doi:10.1172/JCI116480)
25. Henry BA, Goding JW, Tilbrook AJ, Dunshea FR, Blache D & Clarke IJ 2004 Leptin-mediated effects of undernutrition or fasting on luteinizing hormone and growth hormone secretion in ovariectomized ewes depend on the duration of metabolic perturbation. Journal of Neuroendocrinology 16 244-255. (doi:10.1111/j.0953-8194.2004.01157.x)
26. Hintz RL, Suskind R, Amatayakul K, Thanangkul O & Olson R 1978 Plasma somatomedin and growth hormone values in children with protein- calorie malnutrition. Journal of Pediatrics 92 153-156. (doi:10.1016/ S0022-3476(78)80099-7)
27. Ho KY, Veldhuis JD, Johnson ML, Furlanetto R, Evans WS, Alberti KG, Thorner MO 1988 Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man. Journal of Clinical Investigation 81 968-975. (doi:10.1172/JCI113450)
28. Holmes MD, Pollak MN, Willett WC & Hankinson SE 2002 Dietary correlates of plasma insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations. Cancer Epidemiology, Biomarkers & Prevention 11 852-861.
29. Horner JM, Kemp SF & Hintz RL 1981 Growth hormone and somatomedin in insulin-dependent diabetes mellitus. Journal of Clinical Endocrinology and Metabolism 53 1148-1153. (doi:10.1210/jcem-53-6-1148)
30. Hotta M, Fukuda I, Sato K, Hizuka N, Shibasaki T & Takano K 2000 The relationship between bone turnover and body weight, serum insulinlike growth factor (IGF) I, and serum IGF-binding protein levels in patients with anorexia nervosa. Journal of Clinical Endocrinology and Metabolism 85 200-206. (doi:10.1210/jc.85.1.200)
31. Ikeda T, Fujiyama K, Hoshino T, Takeuchi T, Mashiba H & Tominaga M 1990 Possible role of thyroid hormone in decreased somatomedin-C levels in diabetic and starved rats. Annals of Nutrition & Metabolism 34 8-12. (doi:10.1159/000177564)
32. Inagaki T, Dutchak P, Zhao G, Ding X, Gautron L, Parameswara V, Li Y, Goetz R, Mohammadi M, Esser V et al. 2007 Endocrine regulation of the fasting response by PPARa-mediated induction of fibroblast growth factor 21. Cell Metabolism 5 415-425. (doi:10.1016/j.cmet.2007.05.003)
33. Inagaki T, Lin VY, Goetz R, Mohammadi M, Mangelsdorf DJ, Kliewer SA 2008 Inhibition of growth hormone signaling by the fasting-induced hormone FGF21. Cell Metabolism 8 77-83. (doi:10.1016/j.cmet.2008. 05.006)
34. Isley WL, Underwood LE & Clemmons DR 1983 Dietary components that regulate serum somatomedin-C concentrations in humans. Journal of Clinical Investigation 71 175-182. (doi:10.1172/JCI110757)
35. Kaklamani VG, Linos A, Kaklamani E, Markaki I, Koumantaki Y & Mantzoros CS 1999 Dietary fat and carbohydrates are independently associated with circulating insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 concentrations in healthy adults. Journal of Clinical Oncology 17 3291-3298.
36. Keski-Rahkonen A, Hoek HW, Susser ES, Linna MS, Sihvola E, Raevuori A, Bulik CM, Kaprio J & Rissanen A 2007 Epidemiology and course of anorexia nervosa in the community. American Journal of Psychiatry 164 1259-1265. (doi:10.1176/appi.ajp.2007.06081388)
37. Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ, Sandusky GE, Hammond LJ, Moyers JS, Owens RA et al. 2005 FGF-21 as a novel metabolic regulator. Journal of Clinical Investigation 115 1627-1635. (doi:10.1172/JCI23606)
38. Kilic M, Taskin E, Ustundag B & Aygun AD 2004 The evaluation of serum leptin level and other hormonal parameters in children with severe malnutrition. Clinical Biochemistry 37 382-387. (doi:10.1016/j.clinbiochem. 2003.12.010)
39. Klibanski A, Beitins IZ, Badger T, Little R& McArthur JW 1981 Reproductive function during fasting in men. Journal of Clinical Endocrinology and Metabolism 53 258-263. (doi:10.1210/jcem-53-2-258)
40. Kojima M & Kangawa K 2005 Ghrelin: structure and function. Physiological Reviews 85 495-522. (doi:10.1152/physrev.00012.2004)
41. Leung KC, Doyle N, Ballesteros M, Waters MJ & Ho KK 2000 Insulin regulation of human hepatic growth hormone receptors: divergent effects on biosynthesis and surface translocation. Journal of Clinical Endocrinology and Metabolism 85 4712-4720. (doi:10.1210/jc.85.12.4712)
42. Lundasen T, Hunt MC, Nilsson LM, Sanyal S, Angelin B, Alexson SE & Rudling MP 2007 PARa is a key regulator of hepatic FGF21. Biochemical and Biophysical Research Communications 360 437-440. (doi:10.1016/ j.bbrc.2007.06.068)
43. Lundbaek K, Christensen NJ, Jensen VA, Johansen K, Olsen TS, Hansen AP, Orskov H & Osterby R 1970 Diabetes, diabetic angiopathy, and growth hormone. Lancet 2 131-133. (doi:10.1016/S0140-6736(70)92706-6)
44. Maccario M, Valetto MR, Savio P, Aimaretti G, Baffoni C, Procopio M, Grottoli S, Oleandri SE, Arvat E, Ghigo E 1997 Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency. International Journal of Obesity and Related Metabolic Disorders 21 27-32. (doi:10.1038/sj.ijo.0800356)
45. Maes M, Amand Y, Underwood LE, Maiter D & Ketelslegers JM 1988 Decreased serum insulin-like growth factor I response to growth hormone in hypophysectomized rats fed a low protein diet: evidence for a postreceptor defect. Acta Endocrinologica 117 320-326.
46. Maiter D, Fliesen T, Underwood LE, Maes M, Gerard G, Davenport ML & Ketelslegers JM 1989 Dietary protein restriction decreases insulin-like growth factor I independent of insulin and liver growth hormone binding. Endocrinology 124 2604-2611. (doi:10.1210/endo-124-5-2604)
47. Massara F, Ghigo E, Goffi S, Molinatti GM, Muller EE, Camanni F 1984 Blockade of hp-GRF-40-induced GH release in normal men by a cholinergic muscarinic antagonist. Journal of Clinical Endocrinology and Metabolism 59 1025-1026. (doi:10.1210/jcem-59-5-1025)
48. Merimee TJ, Zapf J & Froesch ER 1982 Insulin-like growth factors in the fed and fasted states. Journal of Clinical Endocrinology and Metabolism 55 999-1002. (doi:10.1210/jcem-55-5-999)
49. Miller KK, Lawson EA, Mathur V, Wexler TL, Meenaghan E, Misra M, Herzog DB & Klibanski A 2007 Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea. Journal of Clinical Endocrinology and Metabolism 92 1334-1339. (doi:10. 1210/jc.2006-2501)
50. Misra M, Miller KK, Bjornson J, Hackman A, Aggarwal A, Chung J, Ott M, Herzog DB, Johnson ML & Klibanski A 2003 Alterations in growth hormone secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. Journal of Clinical Endocrinology and Metabolism 88 5615-5623. (doi:10.1210/jc.2003-030532)
51. Mohan PS & Jaya Rao KS 1979 Plasma somatomedin activity in vitamin A deficient children. Clinica Chimica Acta 96 241-246. (doi:10.1016/ 0009-8981(79)90434-0)
52. Mohan PS & Jaya Rao KS 1980 Sulfate metabolism in vitamin A-deficient rats. Journal of Nutrition 110 868-875.
53. Mraz M, Bartlova M, Lacinova Z, Michalsky D, Kasalicky M, Haluzikova D, Matoulek M, Dostalova I, Humenanska V & HaluzikM2009 Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity. Clinical Endocrinology 71 369-375. (doi:10.1111/j.1365-2265.2008.03502.x)
54. Nishimura T, Nakatake Y, Konishi M & Itoh N 2000 Identification of a novel FGF, FGF-21, preferentially expressed in the liver. Biochimica et Biophysica Acta 1492 203-206. (doi:10.1016/S0167-4781(00)00067-1)
55. Olusi SO, Orrell DH, Morris PM & McFarlane H 1977 A study of endocrine function in protein-energy malnutrition. Clinica Chimica Acta 74 261-269. (doi:10.1016/0009-8981(77)90293-5)
56. Potthoff MJ, Inagaki T, Satapati S, Ding X, He T, Goetz R, Mohammadi M, Finck BN, Mangelsdorf DJ, Kliewer SA et al. 2009 FGF21 induces PGC-1a and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response. PNAS 106 10853-10858. (doi:10.1073/ pnas.0904187106)
57. Rao KS & Mohan PS 1982 Plasma somatomedin activity, growth-hormone and insulin levels in vitamin B6 deficient rats. Hormone and Metabolic Research 14 580-582. (doi:10.1055/s-2007-1019086)
58. Reeves RD, Dickinson L, Lee J, Kilgore B, Branham B & Elders MJ 1979 Effects of dietary composition on somatomedin activity in growing rats. Journal of Nutrition 109 613-620.
59. Robinson H & Picou D 1977 A comparison of fasting plasma insulin and growth hormone concentrations in marasmic, kwashiorkor, marasmickwashiorkor and underweight children. Pediatric Research 11 637-640. (doi:10.1203/00006450-197705000-00003)
60. Rolla M, Andreoni A, Belliti D, Ferdeghini M, Cristofani R & Muller EE 1990 Effects of cholinergic muscarinic antagonist pirenzepine on GH response to GHRH 1-40 in patients with anorexia nervosa. Endocrinologia Experimentalis 24 195-204.
61. Sakharova AA, Horowitz JF, Surya S, Goldenberg N, Harber MP, Symons K & BarkanA2008Roleof growthhormonein regulating lipolysis, proteolysis, and hepatic glucose production during fasting. Journal of Clinical Endocrinology and Metabolism 93 2755-2759. (doi:10.1210/jc.2008-0079)
62. Scacchi M, Pincelli AI, Caumo A, Tomasi P,Delitala G, Baldi G &Cavagnini F 1997 Spontaneous nocturnal growth hormone secretion in anorexia nervosa. Journal of Clinical Endocrinology and Metabolism 82 3225-3229. (doi:10.1210/jc.82.10.3225)
63. Schurch MA, Rizzoli R, Slosman D, Vadas L, Vergnaud P & Bonjour JP 1998 Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial. Annals of Internal Medicine 128 801-809. (doi:10.7326/0003-4819-128-10- 199805150-00002)
64. Shimizu H, Miyazaki M, Shimomura Y & Kobayashi I 1991 Altered hormonal status in a female deprived of food for 18 days. Journal of Medicine 22 201-210.
65. Soliman AT, Hassan AE, Aref MK, Hintz RL, Rosenfeld RG & Rogol AD 1986 Serum insulin-like growth factors I and II concentrations and growth hormone and insulin responses to arginine infusion in children with protein-energy malnutrition before and after nutritional rehabilitation. Pediatric Research 20 1122-1130. (doi:10.1203/ 00006450-198611000-00012)
66. Soliman AT, ElZalabany MM, Salama M & Ansari BM 2000 Serum leptin concentrations during severe protein-energy malnutrition: correlation with growth parameters and endocrine function. Metabolism 49 819-825. (doi:10.1053/meta.2000.6745)
67. Stoving RK, Veldhuis JD, Flyvbjerg A, Vinten J, Hangaard J, Koldkjaer OG, Kristiansen J & Hagen C 1999 Jointly amplified basal and pulsatile growth hormone (GH) secretion and increased process irregularity in women with anorexia nervosa: indirect evidence for disruption of feedback regulation within the GH-insulin-like growth factor I axis. Journal of Clinical Endocrinology and Metabolism 84 2056-2063. (doi:10.1210/jc.84.6.2056)
68. Stoving RK, Chen JW, Glintborg D, Brixen K, Flyvbjerg A, Horder K & Frystyk J 2007 Bioactive insulin-like growth factor (IGF) I and IGFbinding protein-1 in anorexia nervosa. Journal of Clinical Endocrinology and Metabolism 92 2323-2329. (doi:10.1210/jc.2006-1926)
69. Straus DS & Takemoto CD 1990 Effect of fasting on insulin-like growth factor-I (IGF-I) and growth hormone receptor mRNA levels and IGF-I gene transcription in rat liver. Molecular Endocrinology 4 91-100. (doi:10.1210/mend-4-1-91)
70. Tamai H, Komaki G, Matsubayashi S, Kobayashi N, Mori K, Nakagawa T, Truong MP, Walter RM Jr & Kumagai LF 1990 Effect of cholinergic muscarinic receptor blockade on human growth hormone (GH)- releasing hormone-(1-44)-induced GH secretion in anorexia nervosa. Journal of Clinical Endocrinology and Metabolism 70 738-741. (doi:10.1210/jcem-70-3-738)
71. Tamai H, Kiyohara K, Mukuta T, Kobayashi N, Komaki G, Nakagawa T, Kumagai LF & Aoki TT 1991 Responses of growth hormone and cortisol to intravenous glucose loading test in patients with anorexia nervosa. Metabolism 40 31-34. (doi:10.1016/0026-0495(91)90188-3)
72. Thimmarayappa J, Sun J, Schultz LE, Dejkhamron P, Lu C, Giallongo A, Merchant JL & Menon RK 2006 Inhibition of growth hormone receptor gene expression by saturated fatty acids: role of Kruppel-like zinc finger factor, ZBP-89. Molecular Endocrinology 20 2747-2760. (doi:10.1210/ me.2006-0128)
73. Thissen JP, Triest S, Underwood LE, Maes M & Ketelslegers JM 1990 Divergent responses of serum insulin-like growth factor-I and liver growth hormone (GH) receptors to exogenous GH in protein-restricted rats. Endocrinology 126 908-913. (doi:10.1210/endo-126-2-908)
74. Thissen JP, Triest S, Moats-Staats BM, Underwood LE, Mauerhoff T, Maiter D & Ketelslegers JM 1991a Evidence that pretranslational and translational defects decrease serum insulin-like growth factor-I concentrations during dietary protein restriction. Endocrinology 129 429-435. (doi:10.1210/endo-129-1-429)
75. Thissen JP, Underwood LE, Maiter D, Maes M, Clemmons DR & Ketelslegers JM 1991b Failure of insulin-like growth factor-I (IGF-I) infusion to promote growth in protein-restricted rats despite normalization of serum IGF-I concentrations. Endocrinology 128 885-890. (doi:10.1210/endo-128-2-885)
76. Yamamoto M, Iguchi G, Fukuoka H, Suda K, Bando H, Takahashi M, Nishizawa H, Seino S & Takahashi Y 2013 SIRT1 regulates adaptive response of the growth hormone - insulin-like growth factor-I axis under fasting conditions in liver. PNAS 110 14948-14953. (doi:10.1073/pnas.1220606110)
77. Yde H 1969 The growth hormone dependent sulfation factor in serum from patients with various types of diabetes. Acta Medica Scandinavica 186 293-297. (doi:10.1111/j.0954-6820.1969.tb01479.x)
78. Yi CX, Heppner KM, Kirchner H, Tong J, Bielohuby M, Gaylinn BD, Muller TD, Bartley E, Davis HW, Zhao Y et al. 2012 The GOAT-ghrelin system is not essential for hypoglycemia prevention during prolonged calorie restriction. PLoS ONE 7 e32100. (doi:10.1371/journal. pone.0032100)
79. Zhang X, Yeung DC, Karpisek M, Stejskal D, Zhou ZG, Liu F, Wong RL, Chow WS, Tso AW, Lam KS et al. 2008 Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes 57 1246-1253. (doi:10.2337/ db07-1476)
80. Zhao TJ, Liang G, Li RL, Xie X, Sleeman MW, Murphy AJ, Valenzuela DM, Yancopoulos GD, Goldstein JL & Brown MS 2010 Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice. PNAS 107 7467-7472. (doi:10.1073/ pnas.1002271107)