Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth

Nutrition Journal

Volumn 12, Issue 1, 2013, Pages

  Melnik, Bodo C ^a   John, Swen Malte ^a   Schmitz, Gerd ^b  

^a UNIVERSITY OF OSNABRÜCK   (Germany)

^b UNIVERSITY HOSPITAL REGENSBURG   (Germany)

Author keywords

Branched chain amino acids; Diseases of civilization; Exosomal microRNA; Glucagon like peptide 1; Glucose dependent insulinotropic polypeptide; Leucine; MicroRNA 21; Milk; mTORC1; Postnatal growth; Tryptophan

Indexed keywords

AMINO ACID; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON LIKE PEPTIDE 1; GROWTH HORMONE; INSULIN; LEUCINE; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MICRORNA; MICRORNA 103; MICRORNA 155; MICRORNA 21; MICRORNA 29A; MICRORNA 29B; SOMATOMEDIN C; TRYPTOPHAN; UNCLASSIFIED DRUG;

ADIPOGENESIS; ADULTHOOD; BREAST MILK; CELL GROWTH; CELL PROLIFERATION; CIVILIZATION; DISEASES; EXOSOME; FOOD; FOOD INTAKE; GENETIC TRANSFECTION; GROWTH HORMONE BLOOD LEVEL; HORMONE BLOOD LEVEL; HUMAN; INSULIN BLOOD LEVEL; INSULIN RESISTANCE; METABOLIC REGULATION; MILK; POSTNATAL GROWTH; PROTEIN BLOOD LEVEL; REVIEW;

AMINO ACIDS; ANIMALS; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON-LIKE PEPTIDE 1; HUMAN GROWTH HORMONE; HUMANS; INFANT; INFANT NUTRITIONAL PHYSIOLOGICAL PHENOMENA; INSULIN; INSULIN-LIKE GROWTH FACTOR I; MICRORNAS; MILK; MILK, HUMAN; MULTIPROTEIN COMPLEXES; POSTNATAL CARE; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; TRANSFECTION; UP-REGULATION;

EID: 84880912548     PISSN: None     EISSN: 14752891     Source Type: Journal    
DOI: 10.1186/1475-2891-12-103     Document Type: Review

References (123)

1. Breastfeeding and maternal and infant health outcomes in developed countries. Ip S, Chung M, Raman G, Chew P, Magula N, DeVine D, Trikalinos T, Lau J, Evid RepTechnol Assess (Full Rep) 2007 153 1 186
2. Cow milk consumption, insulin-like growth factor-I, and human biology: a life history approach. Wiley AS, Am J Hum Biol 2012 24 130 138 10.1002/ajhb.22201 22121110
3. Leucine and mTORC1: a complex relationship. Dodd KM, Tee AR, Am J Physiol Endocrinol Metab 2012 302 1329 E1342 10.1152/ajpendo.00525.2011 22354780
4. Connecting mTORC1 signalling to SREBP-1 activation. Bakan I, Laplante M, Curr Opin Lipidol 2012 23 226 234 10.1097/MOL.0b013e328352dd03 22449814
5. Mammalian target of rapamycin (mTOR): conducting the cellular signalling symphony. Foster KG, Fingar DC, J Biol Chem 2010 285 14071 14077 10.1074/jbc.R109.094003 20231296
6. Amino acids: metabolism, functions, and nutrition. Wu G, Amino Acids 2009 37 1 17 19301095
7. Dietary amino acids and brain serotonin function; implications for stress-related affective changes. Markus CR, Neuromol Med 2008 10 247 258 10.1007/s12017-008-8039-9
8. Effect of 1-5 hydroxytryptophan infusion on growth hormone and prolactin secretion in man. Lancranjan I, Wirz-Justice A, Pühringer W, del Pozo E, J Clin Endocrinol Metab 1977 45 588 593 10.1210/jcem-45-3-588 302840 (Pubitemid 8194499)
9. Milk consumption and the prepubertal somatotropic axis. Rich-Edwards JW, Ganmaa D, Pollak MN, Nakamoto EK, Kleinman K, Tserendolgor U, Willet WC, Frazier AL, Nutr J 2007 6 28 10.1186/1475-2891-6-28 17900364 (Pubitemid 350209637)
10. Differential effects of casein versus whey on fasting plasma levels of insulin, IGF-1 and IGF-1/IGFBP-3: results from a randomized 7-day supplementation study in prepubertal boys. Hoppe C, Mølgaard C, Dalum C, Vaag A, Michaelsen KF, Eur J Clin Nutr 2009 63 1076 1083 10.1038/ejcn.2009.34 19471293
11. Diet, serum insulin-like growth factor-I and IGF-binding protein-3 in European women. Norat T, Dossus L, Rinaldi S, Overvad K, Grønbaek H, Tjønneland A, Olsen A, Clavel-Chapelon F, Boutron-Ruault MC, Boeing H, Lahmann PH, Linseisen J, Nagel G, Trichopoulou A, Trichopoulos D, Kalapothaki V, Sieri S, Palli D, Panico S, Tumino R, Sacerdote C, Bueno-de-Mesquita HB, Peeters PH, van Gils CH, Agudo A, Amiano P, Ardanoz E, Martinez C, Quirós R, Tormo MJ, et al. Eur J Clin Nutr 2007 61 91 98 10.1038/sj.ejcn.1602494 16900085 (Pubitemid 44921120)
12. The association between diet and serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in the European Prospective Investigation into Cancer and Nutrition. Crowe FL, Key TJ, Allen NE, Appleby PN, Roddam A, Overvad K, Grønbaek H, Tjønneland A, Halkjaer J, Dossus L, Boeing H, Kröger J, Trichopoulou A, Dilis V, Trichopoulos D, Boutron-Ruault MC, De Lauzon B, Clavel-Chapelon F, Palli D, Berrino F, Panico S, Tumino R, Sacerdote C, Bueno-de-Mesquita HB, Vrieling A, van Gils CH, Peeters PH, Gram IT, Skeie G, Lund E, et al. Cancer Epidemiol Biomarkers Prev 2009 18 1333 1340 10.1158/1055-9965.EPI-08-0781 19423514
13. Milk consumption and circulating insulin-like growth factor-I level: a systematic literature review. Qin LQ, He K, Xu JY, Int J Food Sci Nutr 2009 60 Suppl 7 330 340 19746296
14. Milk protein intake, the metabolic-endocrine response, and growth in infancy: data from a randomized clinical trial. Socha P, Grote V, Gruszfeld D, Janas R, Demmelmair H, Closa-Monasterolo R, Subías JE, Scaglioni S, Verduci E, Dain E, Langhendries JP, Perrin E, Koletzko B, European Childhood Obesity Trial Study Group, Am J Clin Nutr 2011 94 Suppl 6 1776S 1784S 21849603
15. Glycemia and insulinemia in healthy subjects after lactose-equivalent meals of milk and other food proteins: the role of plasma amino acids and incretins. Nilsson M, Stenberg M, Frid AH, Holst JJ, Björck IM, Am J Clin Nutr 2004 80 1246 1253 15531672 (Pubitemid 41350685)
16. The insulinogenic effects of whey protein is partially mediated by a direct effect of amino acids and GIP on β-cells. Salehi A, Gunnerud U, Muhammed SJ, Ostman E, Holst JJ, Björck I, Rorsman P, Nutr Metab (Lond) 2012 9 48 10.1186/1743-7075-9-48
17. High intakes of milk, but not meat, increases s-insulin and insulin resistance in 8-year- old boys. Hoppe C, Mølgaard C, Vaag A, Barkholt V, Michaelsen KF, Eur J Clin Nutr 2005 59 393 398 10.1038/sj.ejcn.1602086 15578035 (Pubitemid 40403293)
18. Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro. Chen Q, Reimer RA, Nutrition 2009 25 340 349 10.1016/j.nut.2008.08.012 19036562
19. L-leucine and a nonmetabolized analogue activate pancreatic islet glutamate dehydrogenase. Sener A, Malaisse WJ, Nature 1980 288 187 189 10.1038/288187a0 7001252 (Pubitemid 11212612)
20. Branched-chain amino and keto acid metabolism in pancreatic islets. Malaisse WJ, Adv Enzyme Regul 1986 25 203 217 3544703
21. Regulation of insulin release by factors that also modify glutamate dehydrogenase. Fahien LA, MacDonald MJ, Kmiotek EH, Mertz RJ, Fahien CM, J Biol Chem 1988 263 13610 13614 3047128
22. Metabolic regulation by leucine of translation initiation through the mTOR-signaling pathway by pancreatic β-cells. Xu G, Kwon G, Cruz WS, Marshall CA, McDaniel MK, Diabetes 2001 50 353 360 10.2337/diabetes.50.2.353 11272147 (Pubitemid 32127292)
23. Metabolic and autocrine regulation of the mammalian target of rapamycin by pancreatic β-cells. McDaniel ML, Marshall CA, Pappan KL, Kwon G, Diabetes 2002 51 2877 2885 10.2337/diabetes.51.10.2877 12351422
24. Leucine metabolism in regulation of insulin secretion from pancreatic beta cells. Yang J, Chi Y, Burkhardt BR, Guan Y, Wolf BA, Nutr Rev 2010 68 270 279 10.1111/j.1753-4887.2010.00282.x 20500788
25. mTORC1 and mTORC2 regulate insulin secretion through Akt in INS-1 cells. Le Bacquer O, Queniat G, Gmyr V, Kerr-Conte J, Lefebvre B, Pattou F, J Endocrinol 2013 216 21 29 10.1530/JOE-12-0351 23092880
26. Chronic leucine supplementation increases body weight and insulin sensitivity in rats on high-fat diet likely by promoting insulin signalling in insulin-target tissues. Li X, Wang X, Liu R, Ma Y, Guo H, Hao L, Yao P, Liu L, Sun X, He K, Cao W, Yang X, Mol Nutr Food Res 2013 57 1067 1079 10.1002/mnfr.201200311 23404947
27. Whey protein ingestion activates mTOR-dependent signalling after resistance exercise in young men: a double-blinded randomized controlled trial. Farnfield MM, Carey KA, Gran P, Trenerry MK, Cameron-Smith D, Nutrients 2009 1 263 275 10.3390/nu1020263 22253983
28. The effects of energy source and tryptophan on the rate of protein synthesis and on hormones of the entero-insular axis in the piglet. Ponter AA, Cortamira NO, Sève B, Salter DN, Morgan LM, Br J Nutr 1994 71 661 674 10.1079/BJN19940174 8054322 (Pubitemid 24155484)
29. Intragastric tryptophan reduces glycemia after glucose, possibly via glucose-mediated insulinotropic polypeptide in early-weaned piglets. Ponter AA, Sève B, Morgan LM, J Nutr 1994 124 259 267 8308575 (Pubitemid 24093965)
30. Glucose-induced incretin hormone release and inactivation are differently modulated by oral fat and protein in mice. Gunnarsson TP, Sörhed Winzell M, Deacon CF, Larson MO, Jelic K, Carr RD, Ahrén B, Endocrinology 2006 147 3173 3180 10.1210/en.2005-1442 16627575 (Pubitemid 43901106)
31. The glucose-dependent insulinotropic polypeptide receptor is overexpressed amongst GNAS1 mutation-negative somatotropinomas and drives growth hormone (GH)-promoter activity in GH3 cells. Occhi G, Losa M, Albiger N, Trivellin G, Regazzo D, Scanarini M, Monteserin- Garcia JL, Fröhlich B, Ferasin S, Terreni MR, Fassina A, Vitiello L, Stalla G, Mantero F, Scaroni C, J Neuroendocrinol 2011 23 641 649 10.1111/j.1365-2826.2011.02155.x 21554434
32. Nutrition and somatomedin. XXIII. Molecular regulation of IGF-1 by amino acid availability in cultured hepatocytes. Harp JB, Goldstein S, Phillips LS, Diabetes 1991 40 95 101 10.2337/diabetes.40.1.95 1901809
33. Growth hormone and amino acid supply interact synergistically to control insulin-like growth factor-I production and gene expression in cultured ovine hepatocytes. Wheelhouse NM, Stubbs AK, Lomax MA, MacRae JC, Hazlerigg DG, J Endocrinol 1999 163 353 361 10.1677/joe.0.1630353 10556786
34. Differential regulation of insulin-like growth factor I (IGF-I) and IGF binding protein-1 messenger ribonucleic acids by amino acid availability and growth hormone in rat hepatocyte primary culture. Thissen JP, Pucilowska JB, Underwood LE, Endocrinology 1994 134 1570 1576 10.1210/en.134.3.1570 7509741 (Pubitemid 24085618)
35. Nutritional regulation of the insulin-like growth factors. Thissen JP, Ketelslegers JM, Underwood LE, Endocr Rev 1994 15 80 101 8156941 (Pubitemid 24058597)
36. Acute regulation of IGF-1 by alterations in post-exercise macronutrients. Foster EB, Fisher G, Sartin JL, Elsasser TH, Wu G, Cowan W, Pascoe DD, Amino Acids 2012 42 1405 1416 10.1007/s00726-011-0837-y 21293890
37. Insulin regulation of insulin-like growth factor-binding protein-1 gene expression is dependent on the mammalian target of rapamycin, but independent of ribosomal S6 kinase activity. Patel S, Lochhead PA, Rena G, Fumagalli S, Pende M, Kozma SC, Thomas G, Sutherland C, J Biol Chem 2002 277 9889 9895 10.1074/jbc.M109870200 11784721 (Pubitemid 34968094)
38. Regulation and function of insulin-like growth factor-binding protein-1. Lee PDK, Conover CA, Powell DR, Proc Soc Exp Biol Med 1993 204 4 29 10.3181/00379727-204-43630 7690486 (Pubitemid 23274051)
39. Differential effects of insulin-like growth factor-1 (IGF- I) and IGF-binding protein-1 on protein metabolism in human skeletal muscle cells. Frost RA, Lang CH, Endocr Soc 1999 140 3962 3970 10.1210/en.140.9.3962 (Pubitemid 30647090)
40. Effects of caloric or protein restriction on insulin-like growth factor-I (IGF-I) and IGF-binding proteins in children and adults. Smith WJ, Underwood LE, Clemmons DR, J Clin Endocrinol Metab 1995 80 443 449 10.1210/jc.80.2.443 7531712
41. Effects of refeeding of undernourished and insulin treatment of diabetic neonatal rats on IGF and IGFBP. Rivero LGF, Martin MA, Arahuetes R, Hernandez ER, Pascual-Leone AM, Am J Physiol 1996 271 223 E231 8770014
42. Protein quality assessment: impact of expanding understanding of protein and amino acid needs for optimal health. Millward DJ, Layman DK, Tomé D, Schaafsma G, Am J Clin Nutr 2008 87 1576S 1581S 18469291 (Pubitemid 351679814)
43. Over-stimulation of insulin/IGF-1 signalling by Western diet may promote diseases of civilization: lessons learnt from Laron syndrome. Melnik BC, John SW, Schmitz G, Nutr Metab (Lond) 2011 8 41 10.1186/1743-7075-8-41
44. Regulation of mammalian gene expression by exogenous microRNAs. Liang H, Huang L, Cao J, Zen K, Chen X, Zhang CY, WIREs RNA 2012 3 733 742 10.1002/wrna.1127 22740375
45. Secreted microRNAs: a new form of intercellular communication. Chen X, Liang H, Zhang J, Zen K, Zhang CY, Trends Cell Biol 2012 22 125 132 10.1016/j.tcb.2011.12.001 22260888
46. The functions of animal microRNAs. Ambros V, Nature 2004 431 350 355 10.1038/nature02871 15372042 (Pubitemid 39265675)
47. Horizontal transfer of microRNAs: molecular mechanisms and clinical applications. Chen X, Liang H, Zhang J, Zen K, Zhang CY, Protein Cell 2012 3 28 37 10.1007/s13238-012-2003-z 22314808
48. The mircoRNA spectrum in 12 body fluids. Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, Galas DJ, Wang K, Clin Chem 2010 56 1733 1741 10.1373/clinchem.2010.147405 20847327
49. Isolation of bovine milk-derived microvesicles carrying mRNA and microRNAs. Hata T, Murakami K, Nakatani H, Yamamoto Y, Matsuda T, Aoki N, Biochem Biophys Res Commun 2010 396 528 533 10.1016/j.bbrc.2010.04.135 20434431
50. Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products. Chen X, Gao C, Li H, Huang L, Sun Q, Dong Y, Tian C, Gao S, Dong H, Guan D, Hu X, Zhao S, Li L, Zhu L, Yan Q, Zhang J, Zen K, Zhang CY, Cell Res 2010 20 1128 1137 10.1038/cr.2010.80 20548333
51. Bovine milk contains microRNA and messenger RNA that are stable under degradative conditions. Izumi H, Kosaka N, Shimizu T, Sekine K, Ochiya T, Takase M, J Dairy Sci 2012 95 4831 4841 10.3168/jds.2012-5489 22916887
52. Bovine milk exosome proteome. Reinhardt TA, Lippolis JD, Nonnecke BJ, Sacco RE, J Proteomics 2012 75 1486 1492 10.1016/j.jprot.2011.11.017 22129587
53. Purification of RNA from milk whey. Izumi H, Kosala N, Shimizu T, Sekine K, Ochiya T, Takase M, Methods Mol Biol 2013 1024 191 201 10.1007/978-1-62703- 453-1-15 23719952
54. Immune modulatory function of abundant immune-related microRNAs in microvesicles from bovine colostrum. Sun Q, Chen X, Yu J, Ken K, Zhang CY, Li L, Protein Cell 2013 4 197 210 10.1007/s13238-013-2119-9 23483481
55. microRNA as a new immune- regulatory agent in breast milk. Kosaka N, Izumi H, Sekine K, Ochiya T, Silence 2010 1 7 10.1186/1758-907X-1-7 20226005
56. Immune-related microRNAs are abundant in breast milk exosomes. Zhou Q, Li M, Wang X, Li Q, Wang T, Zhu Q, Zhou X, Wang X, Gao X, Li X, Int J Biol Sci 2012 8 118 123 22211110
57. Intestinal epithelial cells secrete exosome-like vesicles. Van Niel G, Raposo G, Candahl C, Boussac M, Hershberg R, Cerf-Bensussan N, Heyman M, Gastroenterology 2001 121 337 349 10.1053/gast.2001.26263 11487543 (Pubitemid 32729381)
58. Exosomal-like vesicles are present in human blood plasma. Caby MP, Lankar D, Vincendeau-Scherrer C, Raposo G, Bonnerot C, Int Immunol 2005 17 879 887 10.1093/intimm/dxh267 15908444 (Pubitemid 41417955)
59. Exosomes: small vesicles participating in intercellular communication. Ludwig AK, Giebel B, Int J Biochem Cell Biol 2012 44 11 15 10.1016/j.biocel. 2011.10.005 22024155
60. Exosomes as intercellular signalling organelles involved in health and disease: basic science and clinical applications. Corrado C, Raimondo S, Chiesi A, Ciccia F, De Leo G, Alessandro R, Int J Mol Sci 2013 14 5338 5366 10.3390/ijms14035338 23466882
61. Age-related differences in the expression of circulating microRNAs: miR-21 as a new circulating marker of inflammaging. Olivieri F, Spazzafumo L, Santini G, Lazzarini R, Albertini MC, Rippo MR, Galeazzi R, Abbatecola AM, Marchesellli F, Monti D, Ostan R, Cevenini E, Antonicelli R, Franceschi C, Procopio AD, Mech Ageing Dev 2012 133 675 685 10.1016/j.mad.2012.09.004 23041385
62. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Zhang L, Hou D, Chen X, Li D, Zhu L, Zhang Y, Li J, Bian Z, Liang X, Cai X, Yin Y, Wang C, Zhang T, Zhu D, Zhang D, Xu J, Chen Q, Ba Y, Liu J, Wang Q, Chen J, Wang J, Wang M, Zhang Q, Zhang J, Zen K, Zhang CY, Cell Res 2012 22 107 126 10.1038/cr.2011.158 21931358
63. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T, Gastroenterology 2007 133 647 658 10.1053/j.gastro.2007.05.022 17681183 (Pubitemid 47187346)
64. Antagonism of miR-21 reverses epithelial-mesenchymal transition and cancer stem cell phenotype through AKT/ERK1/2 incactivation by targeting PTEN. Han M, Liu M, Wang Y, Chen X, Xu J, Sun Y, Zhao L, Qu H, Fan Y, Wu C, PLoS One 2012 7 39520 10.1371/journal.pone.0039520 22761812
65. MicroRNA-21 orchestrates high glucose-induced signals to TOR complex 1, resulting in renal cell pathology in diabetes. Dey N, Das F, Mariappan MM, Mandal CC, Ghosh-Choudhury N, Kasinath BS, Choudhury GG, J Biol Chem 2011 286 25586 25603 10.1074/jbc.M110.208066 21613227
66. TGFβ-stimulated microRNA-21 utilizes PTEN to orchestrate AKT/mTORC1 signaling for mesangial cell hypertrophy and matrix expansion. Dey N, Ghosh-Choudhury N, Kasinath BS, Choudhury GG, PLoS One 2012 7 42316 10.1371/journal.pone.0042316 22879939
67. MicroRNA-21 targets Sprouty2 and promotes cellular outgrouths. Sayed D, Rane S, Lypowy J, He M, Chen IY, Vashistha H, Yan L, Malhotra A, Vatner D, Abdellatif M, Mol Biol Cell 2008 19 3272 3282 10.1091/mbc.E08-02-0159 18508928
68. Transcriptional and post-transcriptional regulation of Sprouty1, a receptor tyrosine kinase inhibitor in prostate cancer. Dariminpourain M, Wang S, Ittmann M, Kwabi-Addo B, Prostate Cancer Prostatic Dis 2011 14 279 285 10.1038/pcan.2011.33 21826097
69. Sprouty keeps bowel kinases regular in colon cancer, while miR-21 targets Sprouty. Frey MR, Carraro G, Batra RK, Polk DB, Warburton D, Cancer Biol Ther 2011 11 122 124 10.4161/cbt.11.1.14176 21124074
70. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, Allgayer H, Oncogene 2008 27 2128 2136 10.1038/sj.onc.1210856 17968323 (Pubitemid 351485639)
71. MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Lu Z, Liu M, Stribinskis V, Klinge CM, Ramos KS, Colburn NH, Li Y, Oncogene 2008 27 4373 4379 10.1038/onc.2008.72 18372920 (Pubitemid 352010003)
72. Suppression of programmed cell death 4 (PDCD4) protein expression by BCR-ABL-regulated engagement of the mTOR/p70 S6 kinase pathway. Carayol N, Katsoulidis E, Sassano A, Altman JK, Druker BJ, Platanias LC, J Biol Chem 2008 283 8601 8610 10.1074/jbc.M707934200 18223253
73. A microRNA-21 surge facilitates rapid cyclin D1 translation and cell cycle progression in mouse liver regeneration. Ng R, Song G, Roll GR, Frandsen NM, Willenbring H, J Clin Invest 2012 122 1097 1108 10.1172/JCI46039 22326957
74. Role of p70S6K1-mediated phosphorylation of eIF4B and PDCD4 proteins in the regulation of protein synthesis. Dennis MD, Jefferson LS, Kimball SR, J Biol Chem 2012 287 42890 42899 10.1074/jbc.M112.404822 23105104
75. Apoptosis and the target genes of miR-21. Becker Buscaglia LE, Li Y, Chin J Cancer 2011 30 371 380 21627859
76. MicroRNA-21 governs TORC1 activation in renal cancer cell proliferation and invasion. Dey N, Das F, Ghosh-Choudhury N, Mandal CC, Parekh DJ, Block K, Kasinath BS, Abboud HA, Chouldhury GG, PLoS One 2012 7 37366 10.1371/journal.pone.0037366 22685542
77. mTOR: from growth signal integration to cancer, diabetes and ageing. Zoncu R, Efeyan A, Sabatini DM, Nat Rev Mol Cell Biol 2011 12 21 35 10.1038/nrm3025 21157483
78. mTOR signalling in health and disease. Proud CG, Biochem Soc Trans 2011 39 431 436 10.1042/BST0390431 21428914
79. Dietary intervention in acne. Attenuation of increased mTORC1 signaling promoted by Western diet. Melnik BC, Dermatoendocrinol 2012 4 20 32 10.4161/derm.19828 22870349
80. Potential role of FoxO1 and mTORC1 in the pathogenesis of Western diet-induced acne. Melnik BC, Zouboulis CC, Exp Dermatol 2013 22 311 315 10.1111/exd.12142 23614736
81. Excessive leucine-mTORC1-signalling of cow milk-based infant formula: the missing link to understand early childhood obesity. Melnik BC, J Obes 2012 2012 197653 22523661
82. Skim milk, whey, and casein increase body weight and whey and casein increase plasma C-peptide concentration in overweight adolescents. Arnberg K, Mølgaard C, Michaelsen KF, Jensen SM, Trolle E, Larnkjær A, J Nutr 2012 142 2083 2090 10.3945/jn.112.161208 23077192
83. Leucine signalling in the pathogenesis of type 2 diabetes and obesity. Melnik BC, World J Diabetes 2012 3 38 53 10.4239/wjd.v3.i3.38 22442749
84. Hypothalamic mTORC1 signalling controls sympathetic nerve activity and arterial pressure and mediates leptin effects. Harlan SM, Guo DF, Morgan DA, Fernandes-Santos C, Rahmouni K, Cell Metabol 2013 17 599 606 10.1016/j.cmet.2013.02.017
85. The role of mTOR signaling in Alzheimer disease. Oddo S, Front Biosci 2012 4 941 952
86. The mTOR signalling pathway in human cancer. Pópulo H, Lopes JM, Soares P, Int J Mol Sci 2012 13 1886 1918 10.3390/ijms13021886 22408430
87. The translational landscape of mTOR signalling steers cancer initiation and metastasis. Hsieh AC, Liu Y, Edlind MP, Ingolia NT, Janes MR, Sher A, Shi EY, Stumpf CR, Christensen C, Bonham MJ, Wang S, Ren P, Martin M, Jessen K, Feldman ME, Weissman JS, Shokat KM, Rommel C, Ruggero D, Nature 2012 485 55 61 10.1038/nature10912 22367541
88. The impact of coẃs milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer. Melnik BC, John SM, Carrera-Bastos P, Cordain L, Nutr Metab (Lond) 2012 9 74 10.1186/1743-7075-9-74
89. Milk kinship hypothesis in light of epigenetic knowledge. Ozkan H, Tuzun F, Kumral A, Duman N, Clin Epigenetics 2012 4 1 14 10.1186/1868-7083-4-14 22989202
90. The Trojan exosome hypothesis. Gould SJ, Booth AM, Hildreth JEK, Proc Natl Acad Sci USA 2003 100 10592 10597 10.1073/pnas.1831413100 12947040 (Pubitemid 37140073)
91. Dairy and milk consumption and child growth: Is BMI involved? An analysis of NHANES 1999-2004. Wiley AS, Am J Hum Biol 2010 22 517 525 10.1002/ajhb.21042 20155844
92. Milk, dairy fat, dietary calcium, and weight gain. Berkey CS, Rocket HRH, Willet WC, Colditz GA, Arch Pediatr Adolesc Med 2005 159 543 550 10.1001/archpedi.159.6.543 15939853 (Pubitemid 40973476)
93. Effects of increased consumption of fluid milk on energy and nutrient intake, body weight, and cardiovascular risk factors in healthy older adults. Barr SI, McCarron DA, Heaney RP, Dawson-Hughes B, Berga SL, Stern JS, Oparil S, Am J Diet Assoc 2000 100 810 817 10.1016/S0002-8223(00)00236-4
94. Milk consumption during pregnancy is associated with increased infant size at birth: prospective cohort study. Olsen SF, Halldorsson TI, Willett WC, Knudsen VK, Gillman MW, Mikkelsen TB, Olsen J, NUTRIX Consortium, Am J Clin Nutr 2007 86 1104 1110 17921389 (Pubitemid 47538314)
95. Does milk and dairy consumption during pregnancy influence fetal growth and infant birthweight? A systematic literature review. Brantsaeter AL, Olafsdottir AS, Forsum E, Olsen SF, Thorsdottir I, Food Nutr Res 2012 56 20050
96. An insulin index of foods: the insulin demand generated by 1000-kJ portions of common foods. Holt S, Brand Miller J, Petocz P, Am J Clin Nutr 1997 66 1264 1276 9356547 (Pubitemid 27473353)
97. Dissociation of the glycaemic and insulinaemic responses to whole and skimmed milk. Hoyt G, Hickey MS, Cordain L, Br J Nutr 2005 93 175 177 10.1079/BJN20041304 15788109
98. The relationship between BMI and metabolomic profiles: a focus on amino acids. Morris C, ÓGrada C, Ryan M, Roche HM, Gibney MJ, Gibney ER, Brennan L, Proc Nutr Soc 2012 71 634 638 10.1017/S0029665112000699 22863201
99. Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents. McCormack SE, Shaham O, McCarthy MA, Deik AA, Wang TJ, Gerszten RE, Clish CB, Mootha VK, Grinspoon SK, Fleischman A, Pediatric Obesity 2013 8 52 61 10.1111/j.2047-6310. 2012.00087.x 22961720
100. MicroRNA regulation in mammalian adipogenesis. Romao JM, Jin W, Dodson MV, Hausman GJ, Moore SS, Guan LL, Exp Biol Med 2011 236 997 1004 10.1258/ebm.2011.011101
101. Mir-21 regulates adipogenic differentiation through the modulation of TGF-β signalling in mesenchymal stem cells derived from human adipose tissue. Kim YJ, Hwang SJ, Bae YC, Jung JS, Stem Cells 2009 27 3093 3102 19816956
102. MicroRNA 21 regulates the proliferation of human adipose tissue-derived mesenchymal stem cells and high-fat diet-induced obesity alters microRNA 21 expression in white adipose tissues. Kim YJ, Hwang SH, Cho HH, Shun KK, Bae YC, Jung JS, J Cell Physiol 2011 227 183 193
103. Mechanistic target of rapamycin (mTOR) controls homeostasis of adipogenesis. Yoon MS, Zhang C, Sun Y, Schoenherr CJ, Chen J, J Lipid Res 2013 54 2166 2173 10.1194/jlr.M037705 23740969
104. S6K1 plays a critical role in early adipocyte differentiation. Carnevalli LS, Masuda K, Frigerio F, Le Bacquer O, Um SH, Gandin V, Topisirovic I, Sonenberg N, Thomas G, Kozma SC, Dev Cell 2010 18 763 774 10.1016/j.devcel.2010. 02.018 20493810
105. MicroRNAs induced during adipogenesis that accelerate fat cell development are downregulated in obesity. Xie H, Lim B, Lodish H, Diabetes 2009 58 1050 1057 10.2337/db08-1299 19188425
106. Early second-trimenster serum miRNA profiling predicts gestational diabetes mellitus. Zhao C, Dong J, Jiang T, Shi Z, Yu B, Zhu Y, Chen D, Xu J, Huo R, Dai J, Xia Y, Pan S, Hu Z, Sha J, PLoS One 2011 6 23925 10.1371/journal.pone.0023925 21887347
107. Insulin-induced gene: a new regulator in lipid metabolism. Dong XY, Tang SQ, Peptides 2010 31 2145 2150 10.1016/j.peptides.2010.07.020 20817058
108. Insig-1 "brakes" lipogenesis in adipocytes and inhibits differentiation of preadipocytes. Li J, Takaishi K, Cook W, McCorkle SK, Unger RU, Proc Natl Acad Sci USA 2003 100 9476 9481 10.1073/pnas.1133426100 12869692 (Pubitemid 37033953)
109. miR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit. Chen Y, Siegel F, Kipschull S, Haas B, Fröhlich H, Meister G, Pfeifer A, Nat Commun 2013 4 1769 23612310
110. Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity. Lackey DE, Lynch CJ, Olson KC, Mostaedi R, Ali M, Smith WH, Karpe F, Humphreys S, Bedinger DH, Dunn TN, Thomas AP, Oort PJ, Kieffer DA, Amin R, Bettaieb A, Haj FG, Permana P, Anthony TG, Adams SH, Am J Physiol Endocrinol Metab 2013 304 1175 E1187 10.1152/ajpendo.00630.2012 23512805
111. Human microRNA (miR29b) expression controls the amount of branched chain α-ketoacid dehydrogenase complex in a cell. Mersey BD, Jin P, Danner DJ, Hum Mol Genet 2005 14 3371 3377 10.1093/hmg/ddi368 16203741 (Pubitemid 41672121)
112. Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1. Um SH, D́Alession D, Thomas G, Cell Metab 2006 3 393 402 10.1016/j.cmet.2006.05.003 16753575 (Pubitemid 43811780)
113. Insulin resistance and the metabolism of branched-chain amino acids. Lu J, Xie G, Jia W, Jia W, Front Med 2013 7 53 59 10.1007/s11684-013-0255-5 23385611
114. A new player in the orchestra of cell growth: SREBP activity is regulated by mTORC1 and contributes to the regulation of cell and organ size. Porstmann T, Santos CR, Lewis C, Griffiths B, Schulze A, Biochme Soc Trans 2009 37 278 283 10.1042/BST0370278
115. An emerging role of mTOR in lipid biosynthesis. Laplante M, Sabatini DM, Curr Biol 2009 19 1046 R1052 10.1016/j.cub.2009.09.058 19948145
116. mTOR complex 1 regulates Lipin1 localization to control the SREBP pathway. Peterson TR, Sengupta SS, Harris TE, Carmack AE, Kang SA, Balderas E, Guertin DA, Madden KL, Carpenter AE, Finck BN, Sabatini DM, Cell 2011 146 408 420 10.1016/j.cell.2011.06.034 21816276
117. Regulation of peroxisome proliferator-activated receptor-γ activity by mammalian target of rapamycin and amino acids in adipogenesis. Kim JE, Chen J, Diabetes 2004 53 2748 2756 10.2337/diabetes.53.11.2748 15504954 (Pubitemid 39425899)
118. Major involvement of mTOR in the PPARγ-induced stimulation of adipose tissue lipid uptake and fat accretion. Blanchard FG, Festuccia WT, Houde VP, St-Pierre P, Brule S, Turcotte V, Cote M, Bellamnn K, Marette A, Deshaies Y, J Lipid Res 2012 53 1117 1125 10.1194/jlr.M021485 22467681
119. Mammalian target of rapamycin complex 1 suppresses lipolysis, stimulates lipogenesis, and promotes fat storage. Chakrabarti P, English T, Shi J, Smas CM, Kandror KV, Diabetes 2010 59 775 781 10.2337/db09-1602 20068142
120. The Lin28/let-7 axis regulates glucose metabolism. Zhu H, Shyh-Chang N, Segrè AV, Shinoda G, Shah SP, Einhorn WS, Takeuchi A, Engreitz JM, Hagan JP, Kharas MG, Urbach A, Thornton JE, Triboulet R, Gregory RI, Altshuler D, Daley GQ, DIAGRAM Consortium, MAGIC Investigators, Cell 2011 147 81 94 10.1016/j.cell.2011.08.033 21962509
121. Selective blockade of microRNA processing by Lin-28. Viswanathan SR, Dalex GQ, Gregory RI, Science 2008 320 97 100 10.1126/science.1154040 18292307 (Pubitemid 351490762)
122. Metabolic rescue of obese adipose-derived stem cells by Lin28/Let7 pathway. Pérez LM, Bernal A, San Martin N, Lorenzo M, Fernández-Veledo S, Gávez BG, Diabetes 2013 62 2368 2379 10.2337/db12-1220 23423565
123. MicroRNA-containing microvesicles regulating inflammation in association with atherosclerotic diesease. Hulsmans M, Holvoet P, Cardiovasc Res 2013 June 16 [Epub ahead of print]