Deficiency in mTORC1-controlled C/EBPβ-mRNA translation improves metabolic health in mice

EMBO Reports

Volumn 16, Issue 8, 2015, Pages 1022-1036

  Zidek, Laura M ^a   Ackermann, Tobias ^b   Hartleben, Götz ^a,b   Eichwald, Sabrina ^a   Kortman, Gertrud ^b   Kiehntopf, Michael ^c   Leutz, Achim ^d   Sonenberg, Nahum ^e   Wang, Zhao Qi ^a   Von Maltzahn, Julia ^a   Müller, Christine ^a,b   Calkhoven, Cornelis F ^a,b  

^a FRITZ LIPMANN INSTITUTE   (Germany)

^b UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^c JENA UNIVERSITY HOSPITAL   (Germany)

^d MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

^e MCGILL UNIVERSITY   (Canada)

Author keywords

C EBP ; calorie restriction; metabolism; mTORC1; translation

Indexed keywords

CCAAT ENHANCER BINDING PROTEIN BETA; INITIATION FACTOR 4E; INITIATION FACTOR 4E BINDING PROTEIN; LIVER INHIBITORY PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MESSENGER RNA; TRANSACTIVATOR PROTEIN; UNCLASSIFIED DRUG; CEBPB PROTEIN, MOUSE; FATTY ACID; ISOPROTEIN; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; RAPAMYCIN; TARGET OF RAPAMYCIN KINASE;

ANIMAL EXPERIMENT; ARTICLE; CALORIC RESTRICTION; GLUCOSE TOLERANCE; INSULIN SENSITIVITY; MOUSE; NONHUMAN; OPEN READING FRAME; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; RNA TRANSLATION; ADIPOGENESIS; ANIMAL; ANTAGONISTS AND INHIBITORS; DEFICIENCY; GENE EXPRESSION REGULATION; GENETICS; LIPID METABOLISM; METABOLISM; OXIDATION REDUCTION REACTION; PROTEIN SYNTHESIS; SIGNAL TRANSDUCTION;

MAMMALIA; MUS; VERTEBRATA;

ADIPOGENESIS; ANIMALS; CALORIC RESTRICTION; CCAAT-ENHANCER-BINDING PROTEIN-BETA; FATTY ACIDS; GENE EXPRESSION REGULATION; LIPID METABOLISM; MICE; MULTIPROTEIN COMPLEXES; OPEN READING FRAMES; OXIDATION-REDUCTION; PHENOTYPE; PROTEIN BIOSYNTHESIS; PROTEIN ISOFORMS; RNA, MESSENGER; SIGNAL TRANSDUCTION; SIROLIMUS; TOR SERINE-THREONINE KINASES;

EID: 84938738838     PISSN: 1469221X     EISSN: 14693178     Source Type: Journal    
DOI: 10.15252/embr.201439837     Document Type: Article

References (44)

1. Desvergne B, Michalik L, Wahli W, (2006) Transcriptional regulation of metabolism. Physiol Rev 86: 465-514
2. Roesler WJ, (2001) The role of C/EBP in nutrient and hormonal regulation of gene expression. Annu Rev Nutr 21: 141-165
3. Descombes P, Schibler U, (1991) A liver-enriched transcriptional activator protein, LAP, and a transcriptional inhibitory protein, LIP, are translated from the same mRNA. Cell 67: 569-579
4. Calkhoven CF, Muller C, Leutz A, (2000) Translational control of C/EBPalpha and C/EBPbeta isoform expression. Genes Dev 14: 1920-1932
5. Wethmar K, Begay V, Smink JJ, Zaragoza K, Wiesenthal V, Dorken B, Calkhoven CF, Leutz A, (2010) C/EBPbetaDeltauORF mice-a genetic model for uORF-mediated translational control in mammals. Genes Dev 24: 15-20
6. Hansen M, Taubert S, Crawford D, Libina N, Lee SJ, Kenyon C, (2007) Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell 6: 95-110
7. Johnson SC, Rabinovitch PS, Kaeberlein M, (2013) mTOR is a key modulator of ageing and age-related disease. Nature 493: 338-345
8. Kaeberlein M, Powers RW III, Steffen KK, Westman EA, Hu D, Dang N, Kerr EO, Kirkland KT, Fields S, Kennedy BK, (2005) Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310: 1193-1196
9. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S, (2004) Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol 14: 885-890
10. Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ, Choudhury AI, Claret M, Al-Qassab H, Carmignac D, Ramadani F, et al, (2009) Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 326: 140-144
11. Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE, Cogger VC, Warren A, Huang X, Pichaud N, Melvin RG, et al, (2014) The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab 19: 418-430
12. Um SH, Frigerio F, Watanabe M, Picard F, Joaquin M, Sticker M, Fumagalli S, Allegrini PR, Kozma SC, Auwerx J, et al, (2004) Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature 431: 200-205
13. Wu JJ, Liu J, Chen EB, Wang JJ, Cao L, Narayan N, Fergusson MM, Rovira II, Allen M, Springer DA, et al, (2013) Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression. Cell Rep 4: 913-920
14. Zid BM, Rogers AN, Katewa SD, Vargas MA, Kolipinski MC, Lu TA, Benzer S, Kapahi P, (2009) 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. Cell 139: 149-160
15. Zoncu R, Efeyan A, Sabatini DM, (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12: 21-35
16. Jundt F, Raetzel N, Muller C, Calkhoven CF, Kley K, Mathas S, Lietz A, Leutz A, Dorken B, (2005) A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein {beta} and NF-{kappa}B activity in Hodgkin and anaplastic large cell lymphomas. Blood 106: 1801-1807
17. Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL, Sabatini DM, (2006) Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 22: 159-168
18. Brunn GJ, Hudson CC, Sekulic A, Williams JM, Hosoi H, Houghton PJ, Lawrence JC Jr, Abraham RT, (1997) Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. Science 277: 99-101
19. Le Bacquer O, Petroulakis E, Paglialunga S, Poulin F, Richard D, Cianflone K, Sonenberg N, (2007) Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2. J Clin Invest 117: 387-396
20. Feldman ME, Apsel B, Uotila A, Loewith R, Knight ZA, Ruggero D, Shokat KM, (2009) Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol 7: e38
21. Bruss MD, Khambatta CF, Ruby MA, Aggarwal I, Hellerstein MK, (2010) Calorie restriction increases fatty acid synthesis and whole body fat oxidation rates. Am J Physiol Endocrinol Metab 298: E108-E116
22. Wernstedt Asterholm I, Scherer PE, (2010) Enhanced metabolic flexibility associated with elevated adiponectin levels. Am J Pathol 176: 1364-1376
23. Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K, Uchida S, Ito Y, Takakuwa K, Matsui J, et al, (2003) Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem 278: 2461-2468
24. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, et al, (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7: 941-946
25. Stefanovic-Racic M, Perdomo G, Mantell BS, Sipula IJ, Brown NF, O'Doherty RM, (2008) A moderate increase in carnitine palmitoyltransferase 1a activity is sufficient to substantially reduce hepatic triglyceride levels. Am J Physiol Endocrinol Metab 294: E969-E977
26. Mulligan JD, Stewart AM, Saupe KW, (2008) Downregulation of plasma insulin levels and hepatic PPARgamma expression during the fir st week of caloric restriction in mice. Exp Gerontol 43: 146-153
27. Higami Y, Pugh TD, Page GP, Allison DB, Prolla TA, Weindruch R, (2004) Adipose tissue energy metabolism: altered gene expression profile of mice subjected to long-term caloric restriction. FASEB J 18: 415-417
28. Selman C, Kerrison ND, Cooray A, Piper MD, Lingard SJ, Barton RH, Schuster EF, Blanc E, Gems D, Nicholson JK, et al, (2006) Coordinated multitissue transcriptional and plasma metabonomic profiles following acute caloric restriction in mice. Physiol Genomics 27: 187-200
29. Huffman DM, Moellering DR, Grizzle WE, Stockard CR, Johnson MS, Nagy TR, (2008) Effect of exercise and calorie restriction on biomarkers of aging in mice. Am J Physiol Regul Integr Comp Physiol 294: R1618-R1627
30. Zhu M, Miura J, Lu LX, Bernier M, DeCabo R, Lane MA, Roth GS, Ingram DK, (2004) Circulating adiponectin levels increase in rats on caloric restriction: the potential for insulin sensitization. Exp Gerontol 39: 1049-1059
31. Katewa SD, Demontis F, Kolipinski M, Hubbard A, Gill MS, Perrimon N, Melov S, Kapahi P, (2012) Intramyocellular fatty-acid metabolism plays a critical role in mediating responses to dietary restriction in Drosophila melanogaster. Cell Metab 16: 97-103
32. Seppala-Lindroos A, Vehkavaara S, Hakkinen AM, Goto T, Westerbacka J, Sovijarvi A, Halavaara J, Yki-Jarvinen H, (2002) Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 87: 3023-3028
33. Neff F, Flores-Dominguez D, Ryan DP, Horsch M, Schröder S, Adler T, Afonso LC, Aguilar-Pimentel JA, Becker L, Garrett L, et al, (2013) Rapamycin extends murine lifespan but has limited effects on aging. J Clin Invest 123: 3272-3291
34. Wilkinson JE, Burmeister L, Brooks SV, Chan CC, Friedline S, Harrison DE, Hejtmancik JF, Nadon N, Strong R, Wood LK, et al, (2012) Rapamycin slows aging in mice. Aging Cell 11: 675-682
35. Bross TG, Rogina B, Helfand SL, (2005) Behavioral, physical, and demographic changes in Drosophila populations through dietary restriction. Aging Cell 4: 309-317
36. McCarter RJ, Shimokawa I, Ikeno Y, Higami Y, Hubbard GB, Yu BP, McMahan CA, (1997) Physical activity as a factor in the action of dietary restriction on aging: effects in Fischer 344 rats. Aging 9: 73-79
37. Weed JL, Lane MA, Roth GS, Speer DL, Ingram DK, (1997) Activity measures in rhesus monkeys on long-term calorie restriction. Physiol Behav 62: 97-103
38. Millward CA, Heaney JD, Sinasac DS, Chu EC, Bederman IR, Gilge DA, Previs SF, Croniger CM, (2007) Mice with a deletion in the gene for CCAAT/enhancer-binding protein beta are protected against diet-induced obesity. Diabetes 56: 161-167
39. Schroeder-Gloeckler JM, Rahman SM, Janssen RC, Qiao L, Shao J, Roper M, Fischer SJ, Lowe E, Orlicky DJ, McManaman JL, et al, (2007) CCAAT/enhancer-binding protein beta deletion reduces adiposity, hepatic steatosis, and diabetes in Lepr(db/db) mice. J Biol Chem 282: 15717-15729
40. Wiederschain D, Wee S, Chen L, Loo A, Yang G, Huang A, Chen Y, Caponigro G, Yao YM, Lengauer C, et al, (2009) Single-vector inducible lentiviral RNAi system for oncology target validation. Cell Cycle 8: 498-504
41. Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, Reichling LJ, Sim T, Sabatini DM, Gray NS, (2009) An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem 284: 8023-8032
42. Fossati P, Prencipe L, (1982) Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem 28: 2077-2080
43. McGowan MW, Artiss JD, Strandbergh DR, Zak B, (1983) A peroxidase-coupled method for the colorimetric determination of serum triglycerides. Clin Chem 29: 538-542
44. Schneider CA, Rasband WS, Eliceiri KW, (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9: 671-675