Beneficial metabolic effects of rapamycin are associated with enhanced regulatory cells in diet-induced obese mice

PLoS ONE

Volumn 9, Issue 4, 2014, Pages

  Makki, Kassem ^a,b,c   Taront, Solenne ^a,b,c   Molendi Coste, Olivier ^b,c,d   Bouchaert, Emmanuel ^b,c,d   Neve, Bernadette ^a,b,c   Eury, Elodie ^a,b,c   Lobbens, Stéphane ^a,b,c   Labalette, Myriam ^b,e   Duez, Hélène ^b,c,d   Staels, Bart ^b,c,d   Dombrowicz, David ^b,c,d   Froguel, Philippe ^a,b,c,f   Wolowczuk, Isabelle ^a,b,c  

^a CNRS   (France)

^b UNIV LILLE   (France)

^c EGID FR3508 European Genomics Institute of Diabetes   (France)

^d INSERM   (France)

^e LILLE UNIVERSITY HOSPITAL   (France)

^f IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; RAPAMYCIN; FAT INTAKE; IMMUNOSUPPRESSIVE AGENT; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MTOR PROTEIN, MOUSE; MULTIPROTEIN COMPLEX; TARGET OF RAPAMYCIN KINASE; TOR COMPLEX 2;

ADIPOSE TISSUE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CALORIMETRY; CONTROLLED STUDY; DRUG EFFECT; ENERGY EXPENDITURE; FEMALE; GLUCOSE TOLERANCE TEST; IMMUNOCOMPETENT CELL; INFLAMMATION; INSULIN RESISTANCE; INSULIN TOLERANCE TEST; LIPID DIET; LIVER; MALE; MOUSE; MUSCLE; MYELOID DERIVED SUPPRESSOR CELL; NONHUMAN; OBESITY; REGULATORY T LYMPHOCYTE; SUPPRESSOR CELL; ADVERSE EFFECTS; ANIMAL; BONE MARROW CELL; CELL PROLIFERATION; CHEMICALLY INDUCED; DISEASE MODEL; DRUG EFFECTS; FAT INTAKE; IMMUNOLOGY; PATHOLOGY; PHARMACOLOGY; SIGNAL TRANSDUCTION;

ADIPOSE TISSUE; ANIMALS; CELL PROLIFERATION; DIETARY FATS; DISEASE MODELS, ANIMAL; FEMALE; IMMUNOSUPPRESSIVE AGENTS; INSULIN RESISTANCE; LIVER; MALE; MICE; MULTIPROTEIN COMPLEXES; MYELOID CELLS; OBESITY; SIGNAL TRANSDUCTION; SIROLIMUS; T-LYMPHOCYTES, REGULATORY; TOR SERINE-THREONINE KINASES;

EID: 84899442976     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0092684     Document Type: Article

References (60)

1. Laplante M, Sabatini DM (2012) mTOR signaling in growth control and disease. Cell 149: 274-293.
2. 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. (Pubitemid 39243474)
3. Khamzina L, Veilleux A, Bergeron S and Marette A (2005) Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: possible involvement in obesity-linked insulin resistance. Endocrinology 146: 1473-1481. (Pubitemid 40289337)
4. Miller JL (1999) Sirolimus approved with renal transplant indication. Am J Health Syst Pharm 56: 2177-2178.
5. Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, et al. (2002) Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 10: 457-468. (Pubitemid 35284167)
6. Ye L, Varamini B, Lamming DW, Sabatini DM, Baur JA (2012) Rapamycin has a biphasic effect on insulin sensitivity in C2C12 myotubes due to sequential disruption of mTORC1 and mTORC2. Front Genet 3: 177.
7. Sabatini DM, Erdjument-Bromage H, Lui M, Tempst P, Snyder SH (1994) RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell 78: 35-43. (Pubitemid 24228298)
8. Kumar A, Harris TE, Keller SR, Choi KM, Magnuson MA, et al. (2008) Muscle-specific deletion of rictor impairs insulin-stimulated glucose transport and enhances Basal glycogen synthase activity. Mol Cell Biol 28: 61-70.
9. Sengupta S, Peterson TR, Laplante M, Oh S, Sabatini DM (2010) mTORC1 controls fasting-induced ketogenesis and its modulation by ageing. Nature 468: 1100-1104.
10. 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.
11. Polak P, Cybulski N, Feige JN, Auwerx J, Ruegg MA, et al. (2008) Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration. Cell Metab 8: 399-410.
12. Le Bacquer O, Petroulakis E, Paglialunga S, Poulin F, Richard D, et al. (2007) Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2. J Clin Invest 117: 387-396. (Pubitemid 46203967)
13. Chang GR, Chiu YS, Wu YY, Chen WY, Liao JW, et al. (2009) Rapamycin protects against high fat diet-induced obesity in C57BL/6J mice. J Pharmacol Sci 109: 496-503.
14. Chang GR, Wu YY, Chiu YS, Chen WY, Liao JW, et al. (2009) Long-term administration of rapamycin reduces adiposity, but impairs glucose tolerance in high-fat diet-fed KK/HlJ mice. Basic Clin Pharmacol Toxicol 105: 188-198.
15. Blagosklonny MV (2011) Rapamycin-induced glucose intolerance: hunger or starvation diabetes. Cell Cycle 10: 4217-4224.
16. Fang Y, Westbrook R, Hill C, Boparai RK, Arum O, et al. (2013) Duration of rapamycin treatment has differential effects on metabolism in mice. Cell Metab 17: 456-462.
17. Houde VP, Brule S, Festuccia WT, Blanchard PG, Bellmann K, et al. (2010) Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue. Diabetes 59: 1338-1348.
18. Lamming DW, Ye L, Astle CM, Baur JA, Sabatini DM, et al. (2013) Young and old genetically heterogeneous HET3 mice on a rapamycin diet are glucose intolerant but insulin sensitive. Aging Cell 12: 712-718.
19. Powell JD, Pollizzi KN, Heikamp EB, Horton MR (2012) Regulation of immune responses by mTOR. Annu Rev Immunol 30: 39-68.
20. Delgoffe GM, Kole TP, Zheng Y, Zarek PE, Matthews KL, et al. (2009) The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 30: 832-844.
21. Delgoffe GM, Pollizzi KN, Waickman AT, Heikamp E, Meyers DJ, et al. (2011) The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat Immunol 12: 295-303.
22. Gabrysova L, Christensen JR, Wu X, Kissenpfennig A, Malissen B, et al. (2011) Integrated T-cell receptor and costimulatory signals determine TGF-beta-dependent differentiation and maintenance of Foxp3+ regulatory T cells. Eur J Immunol 41: 1242-1248.
23. Procaccini C, De Rosa V, Galgani M, Abanni L, Cali G, et al. (2010) An oscillatory switch in mTOR kinase activity sets regulatory T cell responsiveness. Immunity 33: 929-941.
24. Yang H, Youm YH, Vandanmagsar B, Rood J, Kumar KG, et al. (2009) Obesity accelerates thymic aging. Blood 114: 3803-3812.
25. Verwaerde C, Delanoye A, Macia L, Tailleux A, Wolowczuk I (2006) Influence of high-fat feeding on both naive and antigen-experienced T-cell immune response in DO10.11 mice. Scand J Immunol 64: 457-466. (Pubitemid 44536330)
26. Macia L, Delacre M, Abboud G, Ouk TS, Delanoye A, et al. (2006) Impairment of dendritic cell functionality and steady-state number in obese mice. J Immunol 177: 5997-6006. (Pubitemid 44628813)
27. Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, et al. (2006) CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 116: 115-124. (Pubitemid 43121796)
28. Mathis D (2013) Immunological Goings-on in Visceral Adipose Tissue. Cell Metab 17: 851-859.
29. Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259: 87-91. (Pubitemid 23036092)
30. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95: 2409-2415.
31. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, et al. (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112: 1796-1808. (Pubitemid 38063703)
32. Sun S, Ji Y, Kersten S, Qi L (2012) Mechanisms of Inflammatory Responses in Obese Adipose Tissue. Annu Rev Nutr.
33. Xia S, Sha H, Yang L, Ji Y, Ostrand-Rosenberg S, et al. (2011) Gr-1+ CD11b+ myeloid-derived suppressor cells suppress inflammation and promote insulin sensitivity in obesity. J Biol Chem 286: 23591-23599.
34. Peranzoni E, Zilio S, Marigo I, Dolcetti L, Zanovello P, et al. (2011) Myeloid-derived suppressor cell heterogeneity and subset definition. Curr Opin Immunol 22: 238-244.
35. Lees JR, Azimzadeh AM, Bromberg JS (2011) Myeloid derived suppressor cells in transplantation. Curr Opin Immunol 23: 692-697.
36. Chen X, Wu Y, Wang L (2013) Fat-resident Tregs: an emerging guard protecting from obesity-associated metabolic disorders. Obes Rev 14: 568-578.
37. Eller K, Kirsch A, Wolf AM, Sopper S, Tagwerker A, et al. (2011) Potential role of regulatory T cells in reversing obesity-linked insulin resistance and diabetic nephropathy. Diabetes 60: 2954-2962.
38. Thomson AW, Turnquist HR, Raimondi G (2009) Immunoregulatory functions of mTOR inhibition. Nat Rev Immunol 9: 324-337.
39. Elia M, Livesey G (1992) Energy expenditure and fuel selection in biological systems: the theory and practice of calculations based on indirect calorimetry and tracer methods. World Rev Nutr Diet 70: 68-131.
40. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402-408. (Pubitemid 34164012)
41. Minhajuddin M, Fazal F, Bijli KM, Amin MR, Rahman A (2005) Inhibition of mammalian target of rapamycin potentiates thrombin-induced intercellular adhesion molecule-1 expression by accelerating and stabilizing NF-kappa B activation in endothelial cells. J Immunol 174: 5823-5829. (Pubitemid 40593227)
42. Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, et al. (2006) MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 116: 1494-1505.
43. Pederson TM, Kramer DL, Rondinone CM (2001) Serine/threonine phosphorylation of IRS-1 triggers its degradation: possible regulation by tyrosine phosphorylation. Diabetes 50: 24-31. (Pubitemid 32047976)
44. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307: 1098-1101. (Pubitemid 40262113)
45. Bentzinger CF, Romanino K, Cloetta D, Lin S, Mascarenhas JB, et al. (2008) Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy. Cell Metab 8: 411-424.
46. Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, et al. (2007) mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature 450: 736-740. (Pubitemid 350207689)
47. Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, et al. (2012) Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science 335: 1638-1643.
48. Bruun JM, Lihn AS, Verdich C, Pedersen SB, Toubro S, et al. (2003) Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab 285: E527-533. (Pubitemid 37010830)
49. Simons PJ, van den Pangaart PS, Aerts JM, Boon L (2007) Pro-inflammatory delipidizing cytokines reduce adiponectin secretion from human adipocytes without affecting adiponectin oligomerization. J Endocrinol 192: 289-299. (Pubitemid 46444430)
50. Chida D, Osaka T, Hashimoto O, Iwakura Y (2006) Combined interleukin-6 and interleukin-1 deficiency causes obesity in young mice. Diabetes 55: 971-977. (Pubitemid 44100171)
51. Garcia MC, Wernstedt I, Berndtsson A, Enge M, Bell M, et al. (2006) Mature-onset obesity in interleukin-1 receptor I knockout mice. Diabetes 55: 1205-1213. (Pubitemid 44195356)
52. Matsuki T, Horai R, Sudo K, Iwakura Y (2003) IL-1 plays an important role in lipid metabolism by regulating insulin levels under physiological conditions. J Exp Med 198: 877-888. (Pubitemid 37152925)
53. Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, et al. (2002) Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 8: 75-79. (Pubitemid 34101732)
54. Xu H, Hirosumi J, Uysal KT, Guler AD, Hotamisligil GS (2002) Exclusive action of transmembrane TNF alpha in adipose tissue leads to reduced adipose mass and local but not systemic insulin resistance. Endocrinology 143: 1502-1511. (Pubitemid 34274381)
55. Tang T, Zhang J, Yin J, Staszkiewicz J, Gawronska-Kozak B, et al. (2010) Uncoupling of inflammation and insulin resistance by NF-kappaB in transgenic mice through elevated energy expenditure. J Biol Chem 285: 4637-4644.
56. Winer S, Chan Y, Paltser G, Truong D, Tsui H, et al. (2009) Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med 15: 921-929.
57. Procaccini C, De Rosa V, Galgani M, Carbone F, Cassano S, et al. (2012) Leptin-induced mTOR activation defines a specific molecular and transcriptional signature controlling CD4+ effector T cell responses. J Immunol 189: 2941-2953.
58. Zeng H, Yang K, Cloer C, Neale G, Vogel P, et al. (2013) mTORC1 couples immune signals and metabolic programming to establish T(reg)-cell function. Nature 499: 485-490.
59. Fraenkel M, Ketzinel-Gilad M, Ariav Y, Pappo O, Karaca M, et al. (2008) mTOR inhibition by rapamycin prevents beta-cell adaptation to hyperglycemia and exacerbates the metabolic state in type 2 diabetes. Diabetes 57: 945-957.
60. Yang SB, Lee HY, Young DM, Tien AC, Rowson-Baldwin A, et al. (2011) Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity. J Mol Med (Berl) 90: 575-585.