Livers with constitutive mTORC1 activity resist steatosis independent of feedback suppression of akt

PLoS ONE

Volumn 10, Issue 2, 2015, Pages

  Kenerson, Heidi L ^a   Subramanian, Savitha ^a   McIntyre, Rebecca ^a   Kazami, Machiko ^a   Yeung, Raymond S ^a  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARNITINE PALMITOYLTRANSFERASE; CARNITINE PALMITOYLTRANSFERASE 1A; FATTY ACID; GLUCOSE; LIPID; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MEMBRANE PROTEIN; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; PROTEIN TSC1; RAPAMYCIN; S6 KINASE; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; TRANSCRIPTION FACTOR NRF2; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; PTEN PROTEIN, MOUSE; RPS6KA1 PROTEIN, MOUSE; TARGET OF RAPAMYCIN KINASE; TUBEROUS SCLEROSIS COMPLEX 1 PROTEIN; TUMOR SUPPRESSOR PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; ENZYME INHIBITION; FASN GENE; FATTY ACID BLOOD LEVEL; FATTY ACID OXIDATION; FATTY LIVER; GENE; GENE DELETION; GENE EXPRESSION; GENETIC MODEL; GLUCOSE METABOLISM; GLUCOSE TOLERANCE; HISTOPATHOLOGY; IN VIVO STUDY; LIPID DIET; LIPID METABOLISM; LIVER PROTECTION; MALE; MOUSE; NEGATIVE FEEDBACK; NONHUMAN; PROTEIN ANALYSIS; PROTEIN FUNCTION; PROTEIN INDUCTION; SREBP1C GENE; TRIACYLGLYCEROL BLOOD LEVEL; UPREGULATION; ANIMAL; GENETICS; KNOCKOUT MOUSE; LIPOGENESIS; LIVER; METABOLISM; NONALCOHOLIC FATTY LIVER; PATHOLOGY;

MUS;

ANIMALS; DIET, HIGH-FAT; GENE DELETION; LIPOGENESIS; LIVER; MICE; MICE, KNOCKOUT; MULTIPROTEIN COMPLEXES; NON-ALCOHOLIC FATTY LIVER DISEASE; PROTO-ONCOGENE PROTEINS C-AKT; PTEN PHOSPHOHYDROLASE; RIBOSOMAL PROTEIN S6 KINASES, 90-KDA; TOR SERINE-THREONINE KINASES; TUMOR SUPPRESSOR PROTEINS;

EID: 84922374677     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0117000     Document Type: Article

References (36)

1. McCullough AJ (2011) Epidemiology of the metabolic syndrome in the USA. J Dig Dis 12: 333-340. doi: 10.1111/j.1751-2980.2010.00469.x PMID: 21091931
2. Cohen JC, Horton JD, Hobbs HH (2011) Human fatty liver disease: old questions and new insights. Science 332: 1519-1523. doi: 10.1126/science.1204265 PMID: 21700865
3. Li S, Brown MS, Goldstein JL (2010) Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis. Proc Natl Acad Sci U S A 107: 3441-3446. doi: 10.1073/pnas.0914798107 PMID: 20133650
4. Laplante M, Sabatini DM (2010) mTORC1 activates SREBP-1c and uncouples lipogenesis from gluconeogenesis. Proc Natl Acad Sci U S A 107: 3281-3282. doi: 10.1073/pnas.1000323107 PMID: 20167806
5. Quinn WJ III, Birnbaum MJ (2012) Distinct mTORC1 pathways for transcription and cleavage of SREBP-1c. Proc Natl Acad Sci U S A 109: 15974-15975. doi: 10.1073/pnas.1214113109 PMID: 23012450
6. Stiles B, Wang Y, Stahl A, Bassilian S, Lee WP, et al. (2004) Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity [corrected]. Proc Natl Acad Sci U S A 101: 2082-2087. PMID: 14769918
7. Horie Y, Suzuki A, Kataoka E, Sasaki T, Hamada K, et al. (2004) Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J Clin Invest 113: 1774-1783. PMID: 15199412
8. He L, Hou X, Kanel G, Zeng N, Galicia V, et al. (2010) The critical role of AKT2 in hepatic steatosis induced by PTEN loss. Am J Pathol 176: 2302-2308. doi: 10.2353/ajpath.2010.090931 PMID: 20348245
9. Peterson TR, Sengupta SS, Harris TE, Carmack AE, Kang SA, et al. (2011) mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway. Cell 146: 408-420. doi: 10.1016/j.cell.2011.06.034 PMID: 21816276
10. Owen JL, Zhang Y, Bae SH, Farooqi MS, Liang G, et al. (2012) Insulin stimulation of SREBP-1c processing in transgenic rat hepatocytes requires p70 S6-kinase. Proc Natl Acad Sci U S A 109: 16184-16189. doi: 10.1073/pnas.1213343109 PMID: 22927400
11. Dagon Y, Hur E, Zheng B, Wellenstein K, Cantley LC, et al. (2012) p70S6 kinase phosphorylates AMPK on serine 491 to mediate leptin's effect on food intake. Cell Metab 16: 104-112. doi: 10.1016/j. cmet.2012.05.010 PMID: 22727014
12. Kenerson HL, Yeh MM, Yeung RS (2011) Tuberous sclerosis complex-1 deficiency attenuates diet-induced hepatic lipid accumulation. PLoS One 6: e18075. doi: 10.1371/journal.pone.0018075 PMID: 21479224
13. Yecies JL, Zhang HH, Menon S, Liu S, Yecies D, et al. (2011) Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways. Cell Metab 14: 21-32. doi: 10.1016/j.cmet.2011.06.002 PMID: 21723501
14. Huang J, Manning BD (2009) A complex interplay between Akt, TSC2 and the two mTOR complexes. Biochem Soc Trans 37: 217-222. doi: 10.1042/BST0370217 PMID: 19143635
15. Harrington LS, Findlay GM, Gray A, Tolkacheva T, Wigfield S, et al. (2004) The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol 166: 213-223. PMID: 15249583
16. Shah OJ, Wang Z, Hunter T (2004) Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies. Curr Biol 14: 1650-1656. PMID: 15380067
17. Yu Y, Yoon SO, Poulogiannis G, Yang Q, Ma XM, et al. (2011) Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 332: 1322-1326. doi: 10.1126/science.1199484 PMID: 21659605
18. Hsu PP, Kang SA, Rameseder J, Zhang Y, Ottina KA, et al. (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332: 1317-1322. doi: 10.1126/science.1199498 PMID: 21659604
19. Huang J, Dibble CC, Matsuzaki M, Manning BD (2008) The TSC1-TSC2 complex is required for proper activation of mTOR complex 2. Mol Cell Biol 28: 4104-4115. doi: 10.1128/MCB.00289-08 PMID: 18411301
20. Kenerson HL, Yeh MM, Kazami M, Jiang X, Riehle KJ, et al. (2013) Akt and mTORC1 have different roles during liver tumorigenesis in mice. Gastroenterology 144: 1055-1065. doi: 10.1053/j.gastro. 2013.01.053 PMID: 23376645
21. Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226: 497-509. PMID: 13428781
22. Um SH, Frigerio F, Watanabe M, Picard F, Joaquin M, et al. (2004) Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature 431: 200-205. PMID: 15306821
23. Sarbassov dos D, Guertin DA, Ali SM, Sabatini DM (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307: 1098-1101. PMID: 15718470
24. Garcia-Martinez JM, Alessi DR (2008) mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem J 416: 375-385. doi: 10.1042/BJ20081668 PMID: 18925875
25. Sarbassov dos D, Ali SM, Sengupta S, Sheen JH, Hsu PP, et al. (2006) Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 22: 159-168. PMID: 16603397
26. Umemura A, Park EJ, Taniguchi K, Lee JH, Shalapour S, et al. (2014) Liver damage, inflammation, and enhanced tumorigenesis after persistent mTORC1 inhibition. Cell Metab 20: 133-144. doi: 10.1016/j. cmet.2014.05.001 PMID: 24910242
27. Hagiwara A, Cornu M, Cybulski N, Polak P, Betz C, et al. (2012) Hepatic mTORC2 activates glycolysis and lipogenesis through Akt, glucokinase, and SREBP1c. Cell Metab 15: 725-738. doi: 10.1016/j. cmet.2012.03.015 PMID: 22521878
28. Cornu M, OppligerW, Albert V, Robitaille AM, Trapani F, et al. (2014) Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21. Proc Natl Acad Sci U S A 111: 11592-11599. doi: 10.1073/pnas.1412047111 PMID: 25082895
29. Lamle J, Marhenke S, Borlak J, von Wasielewski R, Eriksson CJ, et al. (2008) Nuclear factor-eythroid 2-related factor 2 prevents alcohol-induced fulminant liver injury. Gastroenterology 134: 1159-1168. doi: 10.1053/j.gastro.2008.01.011 PMID: 18395094
30. Chowdhry S, Nazmy MH, Meakin PJ, Dinkova-Kostova AT, Walsh SV, et al. (2010) Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitis. Free Radic Biol Med 48: 357-371. doi: 10.1016/j. freeradbiomed.2009.11.007 PMID: 19914374
31. Kay HY, Kim WD, Hwang SJ, Choi HS, Gilroy RK, et al. (2011) Nrf2 inhibits LXRalpha-dependent hepatic lipogenesis by competing with FXR for acetylase binding. Antioxid Redox Signal 15: 2135-2146. doi: 10.1089/ars.2010.3834 PMID: 21504366
32. Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, et al. (2010) The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol 12: 213-223. doi: 10.1038/ncb2021 PMID: 20173742
33. Cullinan SB, Zhang D, Hannink M, Arvisais E, Kaufman RJ, et al. (2003) Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival. Mol Cell Biol 23: 7198-7209. PMID: 14517290
34. Schieren G, Bolke E, Scherer A, Raffel A, Gerber PA, et al. (2013) Severe everolimus-induced steatohepatis: a case report. Eur J Med Res 18: 22. doi: 10.1186/2047-783X-18-22 PMID: 23822543
35. Jewell JL, Russell RC, Guan KL (2013) Amino acid signalling upstream of mTOR. Nat Rev Mol Cell Biol 14: 133-139. doi: 10.1038/nrm3522 PMID: 23361334
36. Miyake T, Abe M, Furukawa S, Tokumoto Y, Toshimitsu K, et al. (2012) Long-term branched-chain amino acid supplementation improves glucose tolerance in patients with nonalcoholic steatohepatitisrelated cirrhosis. Intern Med 51: 2151-2155. PMID: 22892494