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Published in: Endocrine 3/2017

01-03-2017 | Original Article

AT1 receptor antagonist induces thermogenic beige adipocytes in the inguinal white adipose tissue of obese mice

Authors: Francielle Graus-Nunes, Tamiris Lima Rachid, Felipe de Oliveira Santos, Sandra Barbosa-da-Silva, Vanessa Souza-Mello

Published in: Endocrine | Issue 3/2017

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Abstract

Purpose

To evaluate whether losartan is able to induce beige adipocytes formation, focusing on the thermogenic gene expression and adipocyte remodeling in the subcutaneous white adipose tissue of diet-induced obese mice.

Methods

Male C57BL/6 mice received a control diet (10% energy as lipids) or a high-fat diet (50% energy as lipids) for 10 weeks, followed by a 5-week treatment with losartan: control group, control-losartan group (10 mg/Kg/day), high-fat group and high-fat-losartan group (10 mg/Kg/day). Biochemical, morphometrical, stereological and molecular approaches were used to evaluate the outcomes.

Results

The high-fat diet elicited overweight, insulin resistance and adipocyte hypertrophy in the high-fat group, all of which losartan rescued in the high-fat-losartan group. These effects comply with the induction of beige adipocytes within the inguinal fat pads in high-fat-losartan group as they exhibited the greatest energy expenditure among the groups along with the presence uncoupling protein 1 positive multilocular adipocytes with enhanced peroxisome proliferator-activated receptor gamma coactivator 1-alpha and PR domain containing 16 mRNA levels, indicating a significant potential for mitochondrial biogenesis and adaptive thermogenesis.

Conclusions

Our results show compelling evidence that losartan countered diet-induced obesity in mice by enhancing energy expenditure through beige adipocytes induction. Reduced body mass, increased insulin sensitivity, decreased adipocyte size and marked expression of uncoupling protein 1 by ectopic multilocular adipocytes support these findings. The use of losartan as a coadjutant medicine to tackle obesity and its related disorders merits further investigation.
Literature
1.
go back to reference A. Rodriguez, S. Ezquerro, L. Mendez-Gimenez, S. Becerril, G. Fruhbeck, Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism. Am. J. Physiol. Endocrinol. Metab. 309(8), E691–E714 (2015)CrossRefPubMed A. Rodriguez, S. Ezquerro, L. Mendez-Gimenez, S. Becerril, G. Fruhbeck, Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism. Am. J. Physiol. Endocrinol. Metab. 309(8), E691–E714 (2015)CrossRefPubMed
2.
go back to reference B. Gustafson, S. Hedjazifar, S. Gogg, A. Hammarstedt, U. Smith, Insulin resistance and impaired adipogenesis. Trends Endocrinol. Metab. 26(4), 193–200 (2015)CrossRefPubMed B. Gustafson, S. Hedjazifar, S. Gogg, A. Hammarstedt, U. Smith, Insulin resistance and impaired adipogenesis. Trends Endocrinol. Metab. 26(4), 193–200 (2015)CrossRefPubMed
3.
go back to reference B. Gustafson, U. Smith, Regulation of white adipogenesis and its relation to ectopic fat accumulation and cardiovascular risk. Atherosclerosis 241(1), 27–35 (2015)CrossRefPubMed B. Gustafson, U. Smith, Regulation of white adipogenesis and its relation to ectopic fat accumulation and cardiovascular risk. Atherosclerosis 241(1), 27–35 (2015)CrossRefPubMed
4.
go back to reference V. Peirce, S. Carobbio, A. Vidal-Puig, The different shades of fat. Nature 510(7503), 76–83 (2014)CrossRefPubMed V. Peirce, S. Carobbio, A. Vidal-Puig, The different shades of fat. Nature 510(7503), 76–83 (2014)CrossRefPubMed
5.
go back to reference B.B. Lowell, B.M. Spiegelman, Towards a molecular understanding of adaptive thermogenesis. Nature 404(6778), 652–660 (2000)PubMed B.B. Lowell, B.M. Spiegelman, Towards a molecular understanding of adaptive thermogenesis. Nature 404(6778), 652–660 (2000)PubMed
6.
8.
go back to reference I.G. Shabalina, N. Petrovic, J.M. de Jong, A.V. Kalinovich, B. Cannon, J. Nedergaard, UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic. Cell Rep. 5(5), 1196–1203 (2013)CrossRefPubMed I.G. Shabalina, N. Petrovic, J.M. de Jong, A.V. Kalinovich, B. Cannon, J. Nedergaard, UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic. Cell Rep. 5(5), 1196–1203 (2013)CrossRefPubMed
9.
go back to reference J. Nedergaard, T. Bengtsson, B. Cannon, Unexpected evidence for active brown adipose tissue in adult humans. Am. J. Physiol. Endocrinol. Metab. 293(2), E444–E452 (2007)CrossRefPubMed J. Nedergaard, T. Bengtsson, B. Cannon, Unexpected evidence for active brown adipose tissue in adult humans. Am. J. Physiol. Endocrinol. Metab. 293(2), E444–E452 (2007)CrossRefPubMed
11.
go back to reference V. Souza-Mello, B.M. Gregorio, F.S. Cardoso-de-Lemos, L. de Carvalho, M.B. Aguila, C.A. Mandarim-de-Lacerda, Comparative effects of telmisartan, sitagliptin and metformin alone or in combination on obesity, insulin resistance, and liver and pancreas remodelling in C57BL/6 mice fed on a very high-fat diet. Clin. Sci. (Lond). 119(6), 239–250 (2010)CrossRefPubMed V. Souza-Mello, B.M. Gregorio, F.S. Cardoso-de-Lemos, L. de Carvalho, M.B. Aguila, C.A. Mandarim-de-Lacerda, Comparative effects of telmisartan, sitagliptin and metformin alone or in combination on obesity, insulin resistance, and liver and pancreas remodelling in C57BL/6 mice fed on a very high-fat diet. Clin. Sci. (Lond). 119(6), 239–250 (2010)CrossRefPubMed
12.
go back to reference S. Zhao, L.K. Chan, L. Chen, T.W. Cheng, T. Klein, P.S. Leung, Combination of telmisartan and linagliptin preserves pancreatic islet cell function and morphology in db/db mice. Pancreas 45(4), 584–592 (2016)CrossRefPubMed S. Zhao, L.K. Chan, L. Chen, T.W. Cheng, T. Klein, P.S. Leung, Combination of telmisartan and linagliptin preserves pancreatic islet cell function and morphology in db/db mice. Pancreas 45(4), 584–592 (2016)CrossRefPubMed
13.
go back to reference M.E. Frigolet, N. Torres, A.R. Tovar, The renin-angiotensin system in adipose tissue and its metabolic consequences during obesity. J. Nutr. Biochem. 24(12), 2003–2015 (2013)CrossRefPubMed M.E. Frigolet, N. Torres, A.R. Tovar, The renin-angiotensin system in adipose tissue and its metabolic consequences during obesity. J. Nutr. Biochem. 24(12), 2003–2015 (2013)CrossRefPubMed
14.
go back to reference S. Yasue, H. Masuzaki, S. Okada, T. Ishii, C. Kozuka, T. Tanaka, J. Fujikura, K. Ebihara, K. Hosoda, A. Katsurada, N. Ohashi, M. Urushihara, H. Kobori, N. Morimoto, T. Kawazoe, M. Naitoh, M. Okada, H. Sakaue, S. Suzuki, K. Nakao, Adipose tissue-specific regulation of angiotensinogen in obese humans and mice: impact of nutritional status and adipocyte hypertrophy. Am. J. Hypertens. 23(4), 425–431 (2010)CrossRefPubMedPubMedCentral S. Yasue, H. Masuzaki, S. Okada, T. Ishii, C. Kozuka, T. Tanaka, J. Fujikura, K. Ebihara, K. Hosoda, A. Katsurada, N. Ohashi, M. Urushihara, H. Kobori, N. Morimoto, T. Kawazoe, M. Naitoh, M. Okada, H. Sakaue, S. Suzuki, K. Nakao, Adipose tissue-specific regulation of angiotensinogen in obese humans and mice: impact of nutritional status and adipocyte hypertrophy. Am. J. Hypertens. 23(4), 425–431 (2010)CrossRefPubMedPubMedCentral
15.
go back to reference C.N. Young, D.A. Morgan, S.D. Butler, K. Rahmouni, S.B. Gurley, T.M. Coffman, A.L. Mark, R.L. Davisson, Angiotensin type 1a receptors in the forebrain subfornical organ facilitate leptin-induced weight loss through brown adipose tissue thermogenesis. Mol. Metab. 4(4), 337–343 (2015)CrossRefPubMedPubMedCentral C.N. Young, D.A. Morgan, S.D. Butler, K. Rahmouni, S.B. Gurley, T.M. Coffman, A.L. Mark, R.L. Davisson, Angiotensin type 1a receptors in the forebrain subfornical organ facilitate leptin-induced weight loss through brown adipose tissue thermogenesis. Mol. Metab. 4(4), 337–343 (2015)CrossRefPubMedPubMedCentral
16.
go back to reference K. Araki, T. Masaki, I. Katsuragi, K. Tanaka, T. Kakuma, H. Yoshimatsu, Telmisartan prevents obesity and increases the expression of uncoupling protein 1 in diet-induced obese mice. Hypertension 48(1), 51–57 (2006)CrossRefPubMed K. Araki, T. Masaki, I. Katsuragi, K. Tanaka, T. Kakuma, H. Yoshimatsu, Telmisartan prevents obesity and increases the expression of uncoupling protein 1 in diet-induced obese mice. Hypertension 48(1), 51–57 (2006)CrossRefPubMed
17.
go back to reference P.M. Smith, C.C. Hindmarch, D. Murphy, A.V. Ferguson, AT1 receptor blockade alters nutritional and biometric development in obesity-resistant and obesity-prone rats submitted to a high fat diet. Front. Psychol. 5, 832 (2014)PubMedPubMedCentral P.M. Smith, C.C. Hindmarch, D. Murphy, A.V. Ferguson, AT1 receptor blockade alters nutritional and biometric development in obesity-resistant and obesity-prone rats submitted to a high fat diet. Front. Psychol. 5, 832 (2014)PubMedPubMedCentral
18.
go back to reference A. Penna-de-Carvalho, F. Graus-Nunes, J. Rabelo-Andrade, C.A. Mandarim-de-Lacerda, V. Souza-Mello, Enhanced pan-peroxisome proliferator-activated receptor gene and protein expression in adipose tissue of diet-induced obese mice treated with telmisartan. Exp. Physiol. 99(12), 1663–1678 (2014)CrossRefPubMed A. Penna-de-Carvalho, F. Graus-Nunes, J. Rabelo-Andrade, C.A. Mandarim-de-Lacerda, V. Souza-Mello, Enhanced pan-peroxisome proliferator-activated receptor gene and protein expression in adipose tissue of diet-induced obese mice treated with telmisartan. Exp. Physiol. 99(12), 1663–1678 (2014)CrossRefPubMed
19.
go back to reference A. Katz, S.S. Nambi, K. Mather, A.D. Baron, D.A. Follmann, G. Sullivan, M.J. Quon, Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J. Clin. Endocrinol. Metab. 85(7), 2402–2410 (2000)CrossRefPubMed A. Katz, S.S. Nambi, K. Mather, A.D. Baron, D.A. Follmann, G. Sullivan, M.J. Quon, Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J. Clin. Endocrinol. Metab. 85(7), 2402–2410 (2000)CrossRefPubMed
20.
go back to reference T.C. Bargut, V. Souza-Mello, C.A. Mandarim-de-Lacerda, M.B. Aguila, Fish oil diet modulates epididymal and inguinal adipocyte metabolism in mice. Food Funct. 7(3), 1468–1476 (2016)CrossRefPubMed T.C. Bargut, V. Souza-Mello, C.A. Mandarim-de-Lacerda, M.B. Aguila, Fish oil diet modulates epididymal and inguinal adipocyte metabolism in mice. Food Funct. 7(3), 1468–1476 (2016)CrossRefPubMed
21.
go back to reference T.L. Rachid, A. Penna-de-Carvalho, I. Bringhenti, M.B. Aguila, C.A. Mandarim-de-Lacerda, V. Souza-Mello, Fenofibrate (PPARalpha agonist) induces beige cell formation in subcutaneous white adipose tissue from diet-induced male obese mice. Food Funct. 402, 86–94 (2015) T.L. Rachid, A. Penna-de-Carvalho, I. Bringhenti, M.B. Aguila, C.A. Mandarim-de-Lacerda, V. Souza-Mello, Fenofibrate (PPARalpha agonist) induces beige cell formation in subcutaneous white adipose tissue from diet-induced male obese mice. Food Funct. 402, 86–94 (2015)
22.
go back to reference J.C. Fraulob, R. Ogg-Diamantino, C. Fernandes-Santos, M.B. Aguila, C.A. Mandarim-de-Lacerda, A mouse model of metabolic syndrome: insulin resistance, fatty liver and non-alcoholic fatty pancreas disease (NAFPD) in C57BL/6 mice fed a high fat diet. J. Clin. Biochem. Nutr. 46(3), 212–223 (2010)CrossRefPubMedPubMedCentral J.C. Fraulob, R. Ogg-Diamantino, C. Fernandes-Santos, M.B. Aguila, C.A. Mandarim-de-Lacerda, A mouse model of metabolic syndrome: insulin resistance, fatty liver and non-alcoholic fatty pancreas disease (NAFPD) in C57BL/6 mice fed a high fat diet. J. Clin. Biochem. Nutr. 46(3), 212–223 (2010)CrossRefPubMedPubMedCentral
23.
go back to reference H. He, D. Yang, L. Ma, Z. Luo, S. Ma, X. Feng, T. Cao, Z. Yan, D. Liu, M. Tepel, Z. Zhu, Telmisartan prevents weight gain and obesity through activation of peroxisome proliferator-activated receptor-delta-dependent pathways. Hypertension 55(4), 869–879 (2010)CrossRefPubMed H. He, D. Yang, L. Ma, Z. Luo, S. Ma, X. Feng, T. Cao, Z. Yan, D. Liu, M. Tepel, Z. Zhu, Telmisartan prevents weight gain and obesity through activation of peroxisome proliferator-activated receptor-delta-dependent pathways. Hypertension 55(4), 869–879 (2010)CrossRefPubMed
24.
go back to reference S. Reagan-Shaw, M. Nihal, N. Ahmad, Dose translation from animal to human studies revisited. FASEB J. 22(3), 659–661 (2008)CrossRefPubMed S. Reagan-Shaw, M. Nihal, N. Ahmad, Dose translation from animal to human studies revisited. FASEB J. 22(3), 659–661 (2008)CrossRefPubMed
25.
go back to reference S.L. Hocking, R.L. Stewart, A.E. Brandon, E. Suryana, E. Stuart, E.M. Baldwin, G.A. Kolumam, Z. Modrusan, J.R. Junutula, J.E. Gunton, M. Medynskyj, S.P. Blaber, E. Karsten, B.R. Herbert, D.E. James, G.J. Cooney, M.M. Swarbrick, Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice. Diabetologia 58(7), 1587–1600 (2015)CrossRefPubMed S.L. Hocking, R.L. Stewart, A.E. Brandon, E. Suryana, E. Stuart, E.M. Baldwin, G.A. Kolumam, Z. Modrusan, J.R. Junutula, J.E. Gunton, M. Medynskyj, S.P. Blaber, E. Karsten, B.R. Herbert, D.E. James, G.J. Cooney, M.M. Swarbrick, Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice. Diabetologia 58(7), 1587–1600 (2015)CrossRefPubMed
26.
go back to reference S. Barbosa-da-Silva, J.C. Fraulob-Aquino, J.R. Lopes, C.A. Mandarim-de-Lacerda, M.B. Aguila, Weight cycling enhances adipose tissue inflammatory responses in male mice. PLoS One 7(7), e39837 (2012)CrossRefPubMedPubMedCentral S. Barbosa-da-Silva, J.C. Fraulob-Aquino, J.R. Lopes, C.A. Mandarim-de-Lacerda, M.B. Aguila, Weight cycling enhances adipose tissue inflammatory responses in male mice. PLoS One 7(7), e39837 (2012)CrossRefPubMedPubMedCentral
27.
go back to reference A. Yadav, M.A. Kataria, V. Saini, Role of leptin and adiponectin in insulin resistance. Clin. Chim. Acta 417, 80–84 (2013)CrossRefPubMed A. Yadav, M.A. Kataria, V. Saini, Role of leptin and adiponectin in insulin resistance. Clin. Chim. Acta 417, 80–84 (2013)CrossRefPubMed
28.
go back to reference M.E. Cerf, High fat diet modulation of glucose sensing in the beta-cell. Med. Sci. Monit. 13(1), RA12–17 (2007)PubMed M.E. Cerf, High fat diet modulation of glucose sensing in the beta-cell. Med. Sci. Monit. 13(1), RA12–17 (2007)PubMed
29.
30.
go back to reference S. Kajimura, Engineering fat cell fate to fight obesity and metabolic diseases. Keio J. Med. 64(4), 65 (2015)CrossRefPubMed S. Kajimura, Engineering fat cell fate to fight obesity and metabolic diseases. Keio J. Med. 64(4), 65 (2015)CrossRefPubMed
31.
go back to reference M. Giralt, F. Villarroya, White, brown, beige/brite: different adipose cells for different functions? Endocrinology 154(9), 2992–3000 (2013)CrossRefPubMed M. Giralt, F. Villarroya, White, brown, beige/brite: different adipose cells for different functions? Endocrinology 154(9), 2992–3000 (2013)CrossRefPubMed
32.
go back to reference A. Bartelt, J. Heeren, Adipose tissue browning and metabolic health. Nat. Rev. Endocrinol. 10(1), 24–36 (2014)CrossRefPubMed A. Bartelt, J. Heeren, Adipose tissue browning and metabolic health. Nat. Rev. Endocrinol. 10(1), 24–36 (2014)CrossRefPubMed
33.
go back to reference M. Cedikova, M. Kripnerova, J. Dvorakova, P. Pitule, M. Grundmanova, V. Babuska, D. Mullerova, J. Kuncova, Mitochondria in white, brown, and beige adipocytes. Stem Cells Int. 2016, 6067349 (2016)CrossRefPubMedPubMedCentral M. Cedikova, M. Kripnerova, J. Dvorakova, P. Pitule, M. Grundmanova, V. Babuska, D. Mullerova, J. Kuncova, Mitochondria in white, brown, and beige adipocytes. Stem Cells Int. 2016, 6067349 (2016)CrossRefPubMedPubMedCentral
34.
go back to reference E. Hondares, M. Rosell, J. Diaz-Delfin, Y. Olmos, M. Monsalve, R. Iglesias, F. Villarroya, M. Giralt, Peroxisome proliferator-activated receptor alpha (PPARalpha) induces PPARgamma coactivator 1alpha (PGC-1alpha) gene expression and contributes to thermogenic activation of brown fat: involvement of PRDM16. J. Biol. Chem. 286(50), 43112–43122 (2011)CrossRefPubMedPubMedCentral E. Hondares, M. Rosell, J. Diaz-Delfin, Y. Olmos, M. Monsalve, R. Iglesias, F. Villarroya, M. Giralt, Peroxisome proliferator-activated receptor alpha (PPARalpha) induces PPARgamma coactivator 1alpha (PGC-1alpha) gene expression and contributes to thermogenic activation of brown fat: involvement of PRDM16. J. Biol. Chem. 286(50), 43112–43122 (2011)CrossRefPubMedPubMedCentral
35.
go back to reference A.U. Hasan, K. Ohmori, T. Hashimoto, K. Kamitori, F. Yamaguchi, Y. Ishihara, N. Ishihara, T. Noma, M. Tokuda, M. Kohno, Valsartan ameliorates the constitutive adipokine expression pattern in mature adipocytes: a role for inverse agonism of the angiotensin II type 1 receptor in obesity. Hypertens. Res. 37, 621–628 (2014)CrossRefPubMed A.U. Hasan, K. Ohmori, T. Hashimoto, K. Kamitori, F. Yamaguchi, Y. Ishihara, N. Ishihara, T. Noma, M. Tokuda, M. Kohno, Valsartan ameliorates the constitutive adipokine expression pattern in mature adipocytes: a role for inverse agonism of the angiotensin II type 1 receptor in obesity. Hypertens. Res. 37, 621–628 (2014)CrossRefPubMed
36.
go back to reference X. Palomer, D. Alvarez-Guardia, R. Rodríguez-Calvo, T. Coll, J.C. Laguna, M.M. Davidson, T.O. Chan, A.M. Feldman, M. Vázquez-Carrera, TNF-α reduces PGC1-α expression through NF-KB and p38 MAPK leading to increased oxidation in human cardiac cell model. Cardiovasc. Res. 81, 703–712 (2009)CrossRefPubMed X. Palomer, D. Alvarez-Guardia, R. Rodríguez-Calvo, T. Coll, J.C. Laguna, M.M. Davidson, T.O. Chan, A.M. Feldman, M. Vázquez-Carrera, TNF-α reduces PGC1-α expression through NF-KB and p38 MAPK leading to increased oxidation in human cardiac cell model. Cardiovasc. Res. 81, 703–712 (2009)CrossRefPubMed
37.
go back to reference R.C. Scarpulla, Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian cells. Gene 286(1), 81–89 (2002)CrossRefPubMed R.C. Scarpulla, Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian cells. Gene 286(1), 81–89 (2002)CrossRefPubMed
38.
go back to reference C.A. Piantadosi, H.B. Suliman, Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1. J. Biol. Chem. 281(1), 324–333 (2006)CrossRefPubMed C.A. Piantadosi, H.B. Suliman, Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1. J. Biol. Chem. 281(1), 324–333 (2006)CrossRefPubMed
39.
go back to reference V. Crowley, A.J. Vidal-Puig, Mitochondrial uncoupling proteins (UCPs) and obesity. Nutr. Metab. Cardiovasc. Dis. 11(1), 70–75 (2001)PubMed V. Crowley, A.J. Vidal-Puig, Mitochondrial uncoupling proteins (UCPs) and obesity. Nutr. Metab. Cardiovasc. Dis. 11(1), 70–75 (2001)PubMed
40.
go back to reference S. Keipert, M. Jastroch, Brite/beige fat and UCP1 - is it thermogenesis? Biochim. Biophys. Acta 1837(7), 1075–1082 (2014)CrossRefPubMed S. Keipert, M. Jastroch, Brite/beige fat and UCP1 - is it thermogenesis? Biochim. Biophys. Acta 1837(7), 1075–1082 (2014)CrossRefPubMed
41.
go back to reference S. Kersten, B. Desvergne, W. Wahli, Roles of PPARs in health and disease. Nature 405(6785), 421–424 (2000)CrossRefPubMed S. Kersten, B. Desvergne, W. Wahli, Roles of PPARs in health and disease. Nature 405(6785), 421–424 (2000)CrossRefPubMed
42.
go back to reference P. Bostrom, J. Wu, M.P. Jedrychowski, A. Korde, L. Ye, J.C. Lo, K.A. Rasbach, E.A. Bostrom, J.H. Choi, J.Z. Long, S. Kajimura, M.C. Zingaretti, B.F. Vind, H. Tu, S. Cinti, K. Hojlund, S.P. Gygi, B.M. Spiegelman, A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481(7382), 463–468 (2012)CrossRefPubMedPubMedCentral P. Bostrom, J. Wu, M.P. Jedrychowski, A. Korde, L. Ye, J.C. Lo, K.A. Rasbach, E.A. Bostrom, J.H. Choi, J.Z. Long, S. Kajimura, M.C. Zingaretti, B.F. Vind, H. Tu, S. Cinti, K. Hojlund, S.P. Gygi, B.M. Spiegelman, A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481(7382), 463–468 (2012)CrossRefPubMedPubMedCentral
43.
go back to reference A. Roca-Rivada, C. Castelao, L.L. Senin, M.O. Landrove, J. Baltar, A. Belen Crujeiras, L.M. Seoane, F.F. Casanueva, M. Pardo, FNDC5/irisin is not only a myokine but also an adipokine. PLoS One 8(4), e60563 (2013)CrossRefPubMedPubMedCentral A. Roca-Rivada, C. Castelao, L.L. Senin, M.O. Landrove, J. Baltar, A. Belen Crujeiras, L.M. Seoane, F.F. Casanueva, M. Pardo, FNDC5/irisin is not only a myokine but also an adipokine. PLoS One 8(4), e60563 (2013)CrossRefPubMedPubMedCentral
44.
go back to reference A.B. Crujeiras, M. Pardo, F.F. Casanueva, Irisin: ‘fat’ or artefact. Clin. Endocrinol. (Oxf). 82(4), 467–474 (2015)CrossRefPubMed A.B. Crujeiras, M. Pardo, F.F. Casanueva, Irisin: ‘fat’ or artefact. Clin. Endocrinol. (Oxf). 82(4), 467–474 (2015)CrossRefPubMed
45.
go back to reference M. Li, M. Yang, X. Zhou, X. Fang, W. Hu, W. Zhu, C. Wang, D. Liu, S. Li, H. Liu, G. Yang, L. Li, Elevated circulating levels of irisin and the effect of metformin treatment in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 100(4), 1485–1493 (2015)CrossRefPubMed M. Li, M. Yang, X. Zhou, X. Fang, W. Hu, W. Zhu, C. Wang, D. Liu, S. Li, H. Liu, G. Yang, L. Li, Elevated circulating levels of irisin and the effect of metformin treatment in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 100(4), 1485–1493 (2015)CrossRefPubMed
46.
go back to reference T.J. Kieffer, J.F. Habener, The adipoinsular axis: effects of leptin on pancreatic beta-cells. Am. J. Physiol. Endocrinol. Metab. 278(1), E1–E14 (2000)PubMed T.J. Kieffer, J.F. Habener, The adipoinsular axis: effects of leptin on pancreatic beta-cells. Am. J. Physiol. Endocrinol. Metab. 278(1), E1–E14 (2000)PubMed
48.
go back to reference H. Ohno, K. Shinoda, B.M. Spiegelman, S. Kajimura, PPARgamma agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. Cell Metab. 15(3), 395–404 (2012)CrossRefPubMedPubMedCentral H. Ohno, K. Shinoda, B.M. Spiegelman, S. Kajimura, PPARgamma agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. Cell Metab. 15(3), 395–404 (2012)CrossRefPubMedPubMedCentral
49.
go back to reference J. An, T. Nakajima, K. Kuba, A. Kimura, Losartan inhibits LPS-induced inflammatory signaling through a PPARgamma-dependent mechanism in human THP-1 macrophages. Hypertens. Res. 33(8), 831–835 (2010)CrossRefPubMed J. An, T. Nakajima, K. Kuba, A. Kimura, Losartan inhibits LPS-induced inflammatory signaling through a PPARgamma-dependent mechanism in human THP-1 macrophages. Hypertens. Res. 33(8), 831–835 (2010)CrossRefPubMed
50.
go back to reference E.J. Koh, S.J. Yoon, S.M. Lee, Losartan protects liver against ischaemia/reperfusion injury through PPAR-gamma activation and receptor for advanced glycation end-products down-regulation. Br. J. Pharmacol. 169(6), 1404–1416 (2013)CrossRefPubMedPubMedCentral E.J. Koh, S.J. Yoon, S.M. Lee, Losartan protects liver against ischaemia/reperfusion injury through PPAR-gamma activation and receptor for advanced glycation end-products down-regulation. Br. J. Pharmacol. 169(6), 1404–1416 (2013)CrossRefPubMedPubMedCentral
51.
go back to reference P. Seale, H.M. Conroe, J. Estall, S. Kajimura, A. Frontini, J. Ishibashi, P. Cohen, S. Cinti, B.M. Spiegelman, Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J. Clin. Invest. 121(1), 96–105 (2011)CrossRefPubMed P. Seale, H.M. Conroe, J. Estall, S. Kajimura, A. Frontini, J. Ishibashi, P. Cohen, S. Cinti, B.M. Spiegelman, Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J. Clin. Invest. 121(1), 96–105 (2011)CrossRefPubMed
52.
go back to reference M.J. Harms, J. Ishibashi, W. Wang, H.W. Lim, S. Goyama, T. Sato, M. Kurokawa, K.J. Won, P. Seale, Prdm16 is required for the maintenance of brown adipocyte identity and function in adult mice. Cell. Metab. 19(4), 593–604 (2014)CrossRefPubMedPubMedCentral M.J. Harms, J. Ishibashi, W. Wang, H.W. Lim, S. Goyama, T. Sato, M. Kurokawa, K.J. Won, P. Seale, Prdm16 is required for the maintenance of brown adipocyte identity and function in adult mice. Cell. Metab. 19(4), 593–604 (2014)CrossRefPubMedPubMedCentral
53.
go back to reference P. Cohen, J.D. Levy, Y. Zhang, A. Frontini, D.P. Kolodin, K.J. Svensson, J.C. Lo, X. Zeng, L. Ye, M.J. Khandekar, J. Wu, S.C. Gunawardana, A.S. Banks, J.P. Camporez, M.J. Jurczak, S. Kajimura, D.W. Piston, D. Mathis, S. Cinti, G.I. Shulman, P. Seale, B.M. Spiegelman, Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 156(1-2), 304–316 (2014)CrossRefPubMedPubMedCentral P. Cohen, J.D. Levy, Y. Zhang, A. Frontini, D.P. Kolodin, K.J. Svensson, J.C. Lo, X. Zeng, L. Ye, M.J. Khandekar, J. Wu, S.C. Gunawardana, A.S. Banks, J.P. Camporez, M.J. Jurczak, S. Kajimura, D.W. Piston, D. Mathis, S. Cinti, G.I. Shulman, P. Seale, B.M. Spiegelman, Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 156(1-2), 304–316 (2014)CrossRefPubMedPubMedCentral
54.
go back to reference J. Ishibashi, P. Seale, Functions of Prdm16 in thermogenic fat cells. Temperature 2(1), 65–72 (2015)CrossRef J. Ishibashi, P. Seale, Functions of Prdm16 in thermogenic fat cells. Temperature 2(1), 65–72 (2015)CrossRef
55.
go back to reference B. Cannon, J. Nedergaard, Metabolic consequences of the presence or absence of the thermogenic capacity of brown adipose tissue in mice (and probably in humans). Int. J. Obes. (Lond). 34(Suppl 1), S7–S16 (2010)CrossRef B. Cannon, J. Nedergaard, Metabolic consequences of the presence or absence of the thermogenic capacity of brown adipose tissue in mice (and probably in humans). Int. J. Obes. (Lond). 34(Suppl 1), S7–S16 (2010)CrossRef
56.
go back to reference A.M. Cypess, L.S. Weiner, C. Roberts-Toler, E. Franquet Elia, S.H. Kessler, P.A. Kahn, J. English, K. Chatman, S.A. Trauger, A. Doria, G.M. Kolodny, Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist. Cell Metab. 21, 33–38 (2015)CrossRefPubMedPubMedCentral A.M. Cypess, L.S. Weiner, C. Roberts-Toler, E. Franquet Elia, S.H. Kessler, P.A. Kahn, J. English, K. Chatman, S.A. Trauger, A. Doria, G.M. Kolodny, Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist. Cell Metab. 21, 33–38 (2015)CrossRefPubMedPubMedCentral
57.
go back to reference A.J. Whittle, S. Carobbio, L. Martins, M. Slawik, E. Hondares, M.J. Vazquez, D. Morgan, R.I. Csikasz, R. Gallego, S. Rodriguez-Cuenca, M. Dale, S. Virtue, F. Villarroya, B. Cannon, K. Rahmouni, M. Lopez, A. Vidal-Puig, BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell 149(4), 871–885 (2012)CrossRefPubMedPubMedCentral A.J. Whittle, S. Carobbio, L. Martins, M. Slawik, E. Hondares, M.J. Vazquez, D. Morgan, R.I. Csikasz, R. Gallego, S. Rodriguez-Cuenca, M. Dale, S. Virtue, F. Villarroya, B. Cannon, K. Rahmouni, M. Lopez, A. Vidal-Puig, BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell 149(4), 871–885 (2012)CrossRefPubMedPubMedCentral
58.
59.
go back to reference T.L. Rachid, A. Penna-de-Carvalho, I. Bringhenti, M.B. Aguila, C.A. Mandarim-de-Lacerda, V. Souza-Mello, PPAR-alpha agonist elicits metabolically active brown adipocytes and weight loss in diet-induced obese mice. Cell. Biochem. Funct. 33(4), 249–256 (2015)CrossRefPubMed T.L. Rachid, A. Penna-de-Carvalho, I. Bringhenti, M.B. Aguila, C.A. Mandarim-de-Lacerda, V. Souza-Mello, PPAR-alpha agonist elicits metabolically active brown adipocytes and weight loss in diet-induced obese mice. Cell. Biochem. Funct. 33(4), 249–256 (2015)CrossRefPubMed
60.
go back to reference J. Sanchez-Gurmaches, D.A. Guertin, Adipocyte lineages: tracing back the origins of fat. Biochim. Biophys. Acta 1842(3), 340–351 (2014)CrossRefPubMed J. Sanchez-Gurmaches, D.A. Guertin, Adipocyte lineages: tracing back the origins of fat. Biochim. Biophys. Acta 1842(3), 340–351 (2014)CrossRefPubMed
61.
go back to reference J.Z. Long, K.J. Svensson, L. Tsai, X. Zeng, H.C. Roh, X. Kong, R.R. Rao, J. Lou, I. Lokurkar, W. Baur, J.J. Castellot Jr., E.D. Rosen, B.M. Spiegelman, A smooth muscle-like origin for beige adipocytes. Cell Metab. 19(5), 810–820 (2014)CrossRefPubMedPubMedCentral J.Z. Long, K.J. Svensson, L. Tsai, X. Zeng, H.C. Roh, X. Kong, R.R. Rao, J. Lou, I. Lokurkar, W. Baur, J.J. Castellot Jr., E.D. Rosen, B.M. Spiegelman, A smooth muscle-like origin for beige adipocytes. Cell Metab. 19(5), 810–820 (2014)CrossRefPubMedPubMedCentral
62.
go back to reference J. Wu, P. Bostrom, L.M. Sparks, L. Ye, J.H. Choi, A.H. Giang, M. Khandekar, K.A. Virtanen, P. Nuutila, G. Schaart, K. Huang, H. Tu, W.D. van Marken Lichtenbelt, J. Hoeks, S. Enerback, P. Schrauwen, B.M. Spiegelman, Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150(2), 366–376 (2012)CrossRefPubMedPubMedCentral J. Wu, P. Bostrom, L.M. Sparks, L. Ye, J.H. Choi, A.H. Giang, M. Khandekar, K.A. Virtanen, P. Nuutila, G. Schaart, K. Huang, H. Tu, W.D. van Marken Lichtenbelt, J. Hoeks, S. Enerback, P. Schrauwen, B.M. Spiegelman, Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150(2), 366–376 (2012)CrossRefPubMedPubMedCentral
Metadata
Title
AT1 receptor antagonist induces thermogenic beige adipocytes in the inguinal white adipose tissue of obese mice
Authors
Francielle Graus-Nunes
Tamiris Lima Rachid
Felipe de Oliveira Santos
Sandra Barbosa-da-Silva
Vanessa Souza-Mello
Publication date
01-03-2017
Publisher
Springer US
Published in
Endocrine / Issue 3/2017
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-016-1213-1

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