mTORC1 inhibition with rapamycin exacerbates adipose tissue inflammation in obese mice and dissociates macrophage phenotype from function

Immunobiology

Volumn 222, Issue 2, 2017, Pages 261-271

  Paschoal, Vivian A ^a   Amano, Mariane T ^a   Belchior, Thiago ^a   Magdalon, Juliana ^a   Chimin, Patricia ^a   Andrade, Maynara L ^a   Ortiz Silva, Milene ^a   Castro, Érique ^a   Yamashita, Alex S ^a   Rosa Neto, José Cesar ^a   Câmara, Niels O ^a   Festuccia, William T ^a  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

Adipose tissue inflammation; Cytokines; Macrophages; mTOR; Obesity; Rapamycin

Indexed keywords

GLUCOSE; INTERLEUKIN 10; INTERLEUKIN 13; INTERLEUKIN 1BETA; INTERLEUKIN 4; INTERLEUKIN 6; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MESSENGER RNA; MONOCYTE CHEMOTACTIC PROTEIN 1; RAPAMYCIN; TRANSCRIPTION FACTOR RELA; TUMOR NECROSIS FACTOR; AUTACOID; BIOLOGICAL MARKER; CYTOKINE;

ADIPOSE TISSUE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; BONE MARROW DERIVED MACROPHAGE; CELL POLARITY; CONTROLLED STUDY; CYTOKINE RELEASE; CYTOTOXIC T LYMPHOCYTE; GLUCOSE INTOLERANCE; GLUCOSE METABOLISM; GLUCOSE TOLERANCE; GLYCOLYSIS; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; LIPID DIET; MACROPHAGE; MOUSE; NONHUMAN; OBESITY; PERITONEUM MACROPHAGE; PHAGOCYTOSIS; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; DRUG EFFECTS; IMMUNOLOGY; IMMUNOPHENOTYPING; LEUKOCYTE; METABOLISM; MOUSE MUTANT; PANNICULITIS; PATHOLOGY; PHENOTYPE;

ANIMALS; BIOMARKERS; CYTOKINES; GLUCOSE; IMMUNOPHENOTYPING; INFLAMMATION MEDIATORS; LEUKOCYTES; MACROPHAGES; MACROPHAGES, PERITONEAL; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MICE; MICE, INBRED C57BL; MICE, OBESE; OBESITY; PANNICULITIS; PHENOTYPE; SIROLIMUS;

EID: 85000428204     PISSN: 01712985     EISSN: 18783279     Source Type: Journal    
DOI: 10.1016/j.imbio.2016.09.014     Document Type: Article

References (40)

1. Belchior, T., Paschoal, V.A., Magdalon, J., Chimin, P., Farias, T.M., Chaves-Filho, A.B., Gorjao, R., St-Pierre, P., Miyamoto, S., Kang, J.X., Deshaies, Y., Marette, A., Festuccia, W., Omega-3 fatty acids protect from diet-induced obesity, glucose intolerance, and adipose tissue inflammation through PPARgamma-dependent and PPARgamma-independent actions. Mol. Nutr. Food Res., 59, 2015, 957.
2. Bu, L., Gao, M., Qu, S., Liu, D., Intraperitoneal injection of clodronate liposomes eliminates visceral adipose macrophages and blocks high-fat diet-induced weight gain and development of insulin resistance. AAPS J., 15, 2013, 1001.
3. Cani, P.D., Amar, J., Iglesias, M.A., Poggi, M., Knauf, C., Bastelica, D., Neyrinck, A.M., Fava, F., Tuohy, K.M., Chabo, C., Waget, A., Delmee, E., Cousin, B., Sulpice, T., Chamontin, B., Ferrieres, J., Tanti, J.F., Gibson, G.R., Casteilla, L., Delzenne, N.M., Alessi, M.C., Burcelin, R., Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes, 56, 2007, 1761.
4. Deblon, N., Bourgoin, L., Veyrat-Durebex, C., Peyrou, M., Vinciguerra, M., Caillon, A., Maeder, C., Fournier, M., Montet, X., Rohner-Jeanrenaud, F., Foti, M., Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats. Br. J. Pharmacol., 165, 2012, 2325.
5. Despres, J.P., Lemieux, I., Abdominal obesity and metabolic syndrome. Nature, 444, 2006, 881.
6. El Kasmi, K.C., Qualls, J.E., Pesce, J.T., Smith, A.M., Thompson, R.W., Henao-Tamayo, M., Basaraba, R.J., Konig, T., Schleicher, U., Koo, M.S., Kaplan, G., Fitzgerald, K.A., Tuomanen, E.I., Orme, I.M., Kanneganti, T.D., Bogdan, C., Wynn, T.A., Murray, P.J., Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens. Nat. Immunol., 9, 2008, 1399.
7. Festuccia, W.T., Blanchard, P.G., Richard, D., Deshaies, Y., Basal adrenergic tone is required for maximal stimulation of rat brown adipose tissue UCP1 expression by chronic PPAR-gamma activation. Am. J. Physiol. Regul. Integr. Comp. Physiol., 299, 2010, R159.
8. Festuccia, W.T., Pouliot, P., Bakan, I., Sabatini, D.M., Laplante, M., Myeloid-specific Rictor deletion induces M1 macrophage polarization and potentiates in vivo pro-inflammatory response to lipopolysaccharide. PLoS One, 9, 2014, e95432.
9. Festuccia, W.T., Blanchard, P.G., Belchior, T., Chimin, P., Paschoal, V.A., Magdalon, J., Hirabara, S.M., Simoes, D., St-Pierre, P., Carpinelli, A., Marette, A., Deshaies, Y., PPARgamma activation attenuates glucose intolerance induced by mTOR inhibition with rapamycin in rats. Am. J. Physiol. Endocrinol. Metab., 306, 2014, E1046.
10. Guo, H., Callaway, J.B., Ting, J.P., Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat. Med., 21, 2015, 677.
11. Hotamisligil, G.S., Erbay, E., Nutrient sensing and inflammation in metabolic diseases. Nat. Rev. Immunol., 8, 2008, 923.
12. Hotamisligil, G.S., Shargill, N.S., Spiegelman, B.M., Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science, 259, 1993, 87.
13. Hotamisligil, G.S., Inflammation and metabolic disorders. Nature, 444, 2006, 860.
14. Houde, V.P., Brule, S., Festuccia, W.T., Blanchard, P.G., Bellmann, K., Deshaies, Y., Marette, A., Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue. Diabetes, 59, 2010, 1338.
15. Kelly, B., O'Neill, L.A., Metabolic reprogramming in macrophages and dendritic cells in innate immunity. Cell Res., 25, 2015, 771.
16. Khamzina, L., Veilleux, A., Bergeron, S., Marette, A., 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, 2005, 1473.
17. Lamming, D.W., Ye, L., Katajisto, P., Goncalves, M.D., Saitoh, M., Stevens, D.M., Davis, J.G., Salmon, A.B., Richardson, A., Ahima, R.S., Guertin, D.A., Sabatini, D.M., Baur, J.A., Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science, 335, 2012, 1638.
18. Laplante, M., Sabatini, D.M., mTOR signaling in growth control and disease. Cell, 149, 2012, 274.
19. Lee, D.F., Kuo, H.P., Chen, C.T., Hsu, J.M., Chou, C.K., Wei, Y., Sun, H.L., Li, L.Y., Ping, B., Huang, W.C., He, X., Hung, J.Y., Lai, C.C., Ding, Q., Su, J.L., Yang, J.Y., Sahin, A.A., Hortobagyi, G.N., Tsai, F.J., Tsai, C.H., Hung, M.C., IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway. Cell, 130, 2007, 440.
20. Magdalon, J., Chimin, P., Belchior, T., Neves, R.X., Vieira-Lara, M.A., Andrade, M.L., Farias, T.S., Bolsoni-Lopes, A., Paschoal, V.A., Yamashita, A.S., Kowaltowski, A.J., Festuccia, W.T., Constitutive adipocyte mTORC1 activation enhances mitochondrial activity and reduces visceral adiposity in mice. Biochim. Biophys. Acta, 1861, 2016, 430.
21. Makki, K., Taront, S., Molendi-Coste, O., Bouchaert, E., Neve, B., Eury, E., Lobbens, S., Labalette, M., Duez, H., Staels, B., Dombrowicz, D., Froguel, P., Wolowczuk, I., Beneficial metabolic effects of rapamycin are associated with enhanced regulatory cells in diet-induced obese mice. PLoS One, 9, 2014, e92684.
22. Martin, M., Schifferle, R.E., Cuesta, N., Vogel, S.N., Katz, J., Michalek, S.M., Role of the phosphatidylinositol 3 kinase-Akt pathway in the regulation of IL-10 and IL-12 by Porphyromonas gingivalis lipopolysaccharide. J. Immunol., 171, 2003, 717.
23. Mercalli, A., Calavita, I., Dugnani, E., Citro, A., Cantarelli, E., Nano, R., Melzi, R., Maffi, P., Secchi, A., Sordi, V., Piemonti, L., Rapamycin unbalances the polarization of human macrophages to M1. Immunology, 140, 2013, 179.
24. Michl, J., Ohlbaum, D.J., Silverstein, S.C., 2-Deoxyglucose selectively inhibits Fc and complement receptor-mediated phagocytosis in mouse peritoneal macrophages. I. Description of the inhibitory effect. J. Exp. Med., 144, 1976, 1465.
25. Murray, P.J., Allen, J.E., Biswas, S.K., Fisher, E.A., Gilroy, D.W., Goerdt, S., Gordon, S., Hamilton, J.A., Ivashkiv, L.B., Lawrence, T., Locati, M., Mantovani, A., Martinez, F.O., Mege, J.L., Mosser, D.M., Natoli, G., Saeij, J.P., Schultze, J.L., Shirey, K.A., Sica, A., Suttles, J., Udalova, I., van Ginderachter, J.A., Vogel, S.N., Wynn, T.A., Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity, 41, 2014, 14.
26. Newsholme, P., Gordon, S., Newsholme, E.A., Rates of utilization and fates of glucose, glutamine, pyruvate, fatty acids and ketone bodies by mouse macrophages. Biochem. J., 242, 1987, 631.
27. Ozcan, U., Yilmaz, E., Ozcan, L., Furuhashi, M., Vaillancourt, E., Smith, R.O., Gorgun, C.Z., Hotamisligil, G.S., Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science, 313, 2006, 1137.
28. Rodriguez-Prados, J.C., Traves, P.G., Cuenca, J., Rico, D., Aragones, J., Martin-Sanz, P., Cascante, M., Bosca, L., Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation. J. Immunol., 185, 2010, 605.
29. Sica, A., Mantovani, A., Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest., 122, 2012, 787.
30. Thoreen, C.C., Sabatini, D.M., Rapamycin inhibits mTORC1, but not completely. Autophagy, 5, 2009, 725.
31. Thoreen, C.C., Kang, S.A., Chang, J.W., Liu, Q., Zhang, J., Gao, Y., Reichling, L.J., Sim, T., Sabatini, D.M., Gray, N.S., An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J. Biol. Chem., 284, 2009, 8023.
32. Tsukumo, D.M., Carvalho-Filho, M.A., Carvalheira, J.B., Prada, P.O., Hirabara, S.M., Schenka, A.A., Araujo, E.P., Vassallo, J., Curi, R., Velloso, L.A., Saad, M.J., Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes, 56, 2007, 1986.
33. Um, S.H., Frigerio, F., Watanabe, M., Picard, F., Joaquin, M., Sticker, M., Fumagalli, S., Allegrini, P.R., Kozma, S.C., Auwerx, J., Thomas, G., Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature, 431, 2004, 200.
34. Urano, F., Wang, X., Bertolotti, A., Zhang, Y., Chung, P., Harding, H.P., Ron, D., Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science, 287, 2000, 664.
35. Veilleux, A., Houde, V.P., Bellmann, K., Marette, A., Chronic inhibition of the mTORC1/S6K1 pathway increases insulin-induced PI3K activity but inhibits Akt2 and glucose transport stimulation in 3T3-L1 adipocytes. Mol. Endocrinol., 24, 2010, 766.
36. Venter, G., Oerlemans, F.T., Wijers, M., Willemse, M., Fransen, J.A., Wieringa, B., Glucose controls morphodynamics of LPS-stimulated macrophages. PLoS One, 9, 2014, e96786.
37. Viatour, P., Merville, M.P., Bours, V., Chariot, A., Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation. Trends Biochem. Sci., 30, 2005, 43.
38. Weichhart, T., Saemann, M.D., The multiple facets of mTOR in immunity. Trends Immunol., 30, 2009, 218.
39. Weichhart, T., Hengstschlager, M., Linke, M., Regulation of innate immune cell function by mTOR. Nat. Rev. Immunol., 15, 2015, 599.
40. Weisberg, S.P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R.L., Ferrante, A.W. Jr., Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest., 112, 2003, 1796.