Stimulation of soluble guanylyl cyclase protects against obesity by recruiting brown adipose tissue

Nature Communications

Volumn 6, Issue , 2015, Pages

  Hoffmann, Linda S ^a   Etzrodt, Jennifer ^a   Willkomm, Lena ^b,h   Sanyal, Abhishek ^a,c   Scheja, Ludger ^d   Fischer, Alexander W C ^d   Stasch, Johannes Peter ^e,f   Bloch, Wilhelm ^b   Friebe, Andreas ^g   Heeren, Joerg ^d   Pfeifer, Alexander ^a,c  

^a UNIVERSITY HOSPITAL BONN   (Germany)

^b GERMAN SPORT UNIVERSITY COLOGNE   (Germany)

^c UNIVERSITY OF BONN   (Germany)

^d UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^e BAYER PHARMA AG   (Germany)

^f MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

^g UNIVERSITY OF WÜRZBURG   (Germany)

^h UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

2 [1 (2 FLUOROBENZYL) 1H PYRAZOLO[3,4 B]PYRIDIN 3 YL] 5 MORPHOLINO 4,6 PYRIMIDINEDIAMINE; CYCLIC GMP; GUANYLATE CYCLASE; MORPHOLINE DERIVATIVE; PYRIMIDINE DERIVATIVE;

BIOENERGETICS; DIABETES; ENERGY BALANCE; OBESITY; PHENOTYPE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BROWN ADIPOCYTE; BROWN ADIPOSE TISSUE; CELL DIFFERENTIATION; COMORBIDITY; CONTROLLED STUDY; DIET INDUCED OBESITY; DRUG TARGETING; ENERGY EXPENDITURE; HUMAN; HUMAN CELL; HUMAN TISSUE; LIPID TRANSPORT; MALE; MOUSE; NONHUMAN; PHENOTYPE; WEIGHT GAIN; WEIGHT REDUCTION; WHITE ADIPOCYTE; ADIPOCYTE; ANIMAL; C57BL MOUSE; CELL CULTURE; DRUG EFFECTS; LIPID METABOLISM; METABOLISM; OBESITY; PRECLINICAL STUDY; THERMOGENESIS; WHITE ADIPOSE TISSUE;

ADIPOCYTES; ADIPOSE TISSUE, BROWN; ADIPOSE TISSUE, WHITE; ANIMALS; CELLS, CULTURED; DRUG EVALUATION, PRECLINICAL; GUANYLATE CYCLASE; HUMANS; LIPID METABOLISM; MALE; MICE, INBRED C57BL; MORPHOLINES; OBESITY; PYRIMIDINES; THERMOGENESIS; WEIGHT LOSS;

EID: 84930225128     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms8235     Document Type: Article

References (56)

1. Ng, M. et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the global burden of disease study 2013. Lancet 6736, 60460-60468 (2014).
2. Flegal, K. M., Kit, B. K., Orpana, H. & Graubard, B. I. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA 309, 71-82 (2013).
3. Kwon, H. & Pessin, J. E. Adipokines mediate inflammation and insulin resistance. Front. Endocrinol. (Lausanne) 4, 71 (2013).
4. Cannon, B. & Nedergaard, J. Brown adipose tissue: function and physiological significance. Physiol. Rev. 84, 277-359 (2004).
5. Enerback, S. Human brown adipose tissue. Cell 11, 248-252 (2010).
6. Harms, M. & Seale, P. Brown and beige fat: development, function and therapeutic potential. Nat. Med. 19, 1252-1263 (2013).
7. Kajimura, S. & Saito, M. A new era in brown adipose tissue biology: molecular control of brown fat development and energy homeostasis. Annu. Rev. Physiol. 76, 225-249 (2014).
8. Bartelt, A. & Heeren, J. Adipose tissue browning and metabolic health. Nat. Rev. Endocrinol. 10, 24-36 (2014).
9. Pfeifer, A. & Hoffmann, L. S. Brown, beige, and white: the new color code of fat and its pharmacological implications. Annu. Rev. Pharmacol. Toxicol. 55, 207-227 (2015).
10. Rosen, E. D. & Spiegelman, B. M. What we talk about when we talk about fat. Cell 156, 20-44 (2014).
11. Cypess, A. M. et al. Identification and importance of brown adipose tissue in adult humans. N. Engl. J. Med. 360, 1509-1517 (2009).
12. van Marken Lichtenbelt, W. D. et al. Cold-activated brown adipose tissue in healthy men. N. Engl. J. Med. 360, 1500-1508 (2009).
13. Shimizu, I. et al. Vascular rarefaction mediates whitening of brown fat in obesity. J. Clin. Invest. 124, 2099-2112 (2014).
14. Pfeifer, A., Kilic, A. & Hoffmann, L. S. Regulation of metabolism by cgmp. Pharmacol. Ther. 140, 81-91 (2013).
15. Lo, K. A. & Sun, L. Turning wat into bat: A review on regulators controlling the browning of white adipocytes. Biosci. Rep. 33 (2013).
16. Wu, J., Cohen, P. & Spiegelman, B. M. Adaptive thermogenesis in adipocytes: Is beige the new brown? Genes Dev. 27, 234-250 (2013).
17. Frontini, A. & Cinti, S. Distribution and development of brown adipocytes in the murine and human adipose organ. Cell 11, 253-256 (2010).
18. Nedergaard, J. & Cannon, B. The changed metabolic world with human brown adipose tissue: therapeutic visions. Cell Metab. 11, 268-272 (2010).
19. Gnad, T. et al. Adenosine activates brown adipose tissue and recruits beige adipocytes via a receptors. Nature 516, 395-399 (2014).
20. Haas, B. et al. Protein kinase g controls brown fat cell differentiation and mitochondrial biogenesis. Sci. Signal. 2, ra78 (2009).
21. Nisoli, E. et al. Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science 299, 896-899 (2003).
22. Potter, L. R. Guanylyl cyclase structure, function and regulation. Cell Signal. 23, 1921-1926 (2011).
23. Mitschke, M. M. et al. Increased cgmp promotes healthy expansion and browning of white adipose tissue. FASEB J. 27, 1621-1630 (2013).
24. Roberts, L. D. et al. Inorganic nitrate promotes the browning of white adipose tissue through the nitrate-nitrite-nitric oxide pathway. Diabetes 64, 471-484 (2015).
25. Bordicchia, M. et al. Cardiac natriuretic peptides act via p38 mapk to induce the brown fat thermogenic program in mouse and human adipocytes. J. Clin. Invest. 122, 1022-1036 (2012).
26. Derbyshire, E. R. & Marletta, M. A. Structure and regulation of soluble guanylate cyclase. Annu. Rev. Biochem. 81, 533-559 (2012).
27. Friebe, A., Mergia, E., Dangel, O., Lange, A. & Koesling, D. Fatal gastrointestinal obstruction and hypertension in mice lacking nitric oxidesensitive guanylyl cyclase. Proc. Natl Acad. Sci. USA 104, 7699-7704 (2007).
28. Stasch, J. P., Pacher, P. & Evgenov, O. V. Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease. Circulation 123, 2263-2273 (2011).
29. Stasch, J. P. & Hobbs, A. J. No-independent, haem-dependent soluble guanylate cyclase stimulators. Hand. Exp. Pharmacol. 191, 277-308 (2009).
30. Bartelt, A. et al. Brown adipose tissue activity controls triglyceride clearance. Nat. Med. 17, 200-205 (2011).
31. Puigserver, P. & Spiegelman, B. M. Peroxisome proliferator-activated receptorgamma coactivator 1 alpha (pgc-1 alpha): transcriptional coactivator and metabolic regulator. Endocr. Rev. 24, 78-90 (2003).
32. Nisoli, E. et al. Mitochondrial biogenesis by no yields functionally active mitochondria in mammals. Proc. Natl Acad. Sci. USA 101, 16507-16512 (2004).
33. Mitsuishi, M., Miyashita, K. & Itoh, H. Cgmp rescues mitochondrial dysfunction induced by glucose and insulin in myocytes. Biochem. Biophys. Res. Commun. 367, 840-845 (2008).
34. Miyashita, K. et al. Natriuretic peptides/cgmp/cgmp-dependent protein kinase cascades promote muscle mitochondrial biogenesis and prevent obesity. Diabetes 58, 2880-2892 (2009).
35. Rodriguez, A. M. et al. Transplantation of a multipotent cell population from human adipose tissue induces dystrophin expression in the immunocompetent mdx mouse. J. Exp. Med. 201, 1397-1405 (2005).
36. Sun, K., Kusminski, C. M. & Scherer, P. E. Adipose tissue remodeling and obesity. J. Clin. Invest. 121, 2094-2101 (2011).
37. Khedoe, P. P. et al. Brown adipose takes up plasma triglycerides mostly after lipolysis. J. Lipid Res. 56, 51-59 (2014).
38. Ouellet, V. et al. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J. Clin. Invest. 122, 545-552 (2012).
39. Moro, C., Klimcakova, E., Lafontan, M., Berlan, M. & Galitzky, J. Phosphodiesterase-5a and neutral endopeptidase activities in human adipocytes do not control atrial natriuretic peptide-mediated lipolysis. Br. J. Pharmacol. 152, 1102-1110 (2007).
40. Stasch, J. P. et al. Pharmacological actions of a novel no-independent guanylyl cyclase stimulator, bay 41-8543: in vitro studies. Br. J. Pharmacol. 135, 333-343 (2002).
41. Hoffmann, L. S. et al. Distinct molecular requirements for activation or stabilization of soluble guanylyl cyclase upon haem oxidation-induced degradation. Br. J. Pharmacol. 157, 781-795 (2009).
42. Franca-Silva, M. S. et al. Organic nitrates: past, present and future. Molecules 19, 15314-15323 (2014).
43. Munzel, T., Daiber, A. & Gori, T. More answers to the still unresolved question of nitrate tolerance. Eur. Heart J. 34, 2666-2673 (2014).
44. Sackner-Bernstein, J. D., Kowalski, M., Fox, M. & Aaronson, K. Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials. JAMA 293, 1900-1905 (2005).
45. Sackner-Bernstein, J. D., Skopicki, H. A. & Aaronson, K. D. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation 111, 1487-1491 (2005).
46. Gareri, P., Castagna, A., Francomano, D., Cerminara, G. & De Fazio, P. Erectile dysfunction in the elderly: an old widespread issue with novel treatment perspectives. Int. J. Endocrinol. 2014, 878670 (2014).
47. Ayala, J. E. et al. Chronic treatment with sildenafil improves energy balance and insulin action in high fat-fed conscious mice. Diabetes 56, 1025-1033 (2007).
48. Schwartz, B. G. & Kloner, R. A. Drug interactions with phosphodiesterase-5 inhibitors used for the treatment of erectile dysfunction or pulmonary hypertension. Circulation 122, 88-95 (2010).
49. Kloner, R. A. Cardiovascular effects of the 3 phosphodiesterase-5 inhibitors approved for the treatment of erectile dysfunction. Circulation 110, 3149-3155 (2004).
50. Li, W. Q., Qureshi, A. A., Robinson, K. C. & Han, J. Sildenafil use and increased risk of incident melanoma in us men: a prospective cohort study. JAMA Intern. Med. 174, 964-970 (2014).
51. Mittendorf, J. et al. Discovery of riociguat (bay 63-2521): a potent, oral stimulator of soluble guanylate cyclase for the treatment of pulmonary hypertension. Chem.Med.Chem. 4, 853-865 (2009).
52. Ghofrani, H. A. et al. Riociguat for the treatment of pulmonary arterial hypertension. N. Engl. J. Med. 369, 330-340 (2013).
53. Ghofrani, H. A. et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N. Engl. J. Med. 369, 319-329 (2013).
54. Hoffmann, L. S. & Chen, H. H. Cgmp: transition from bench to bedside: A report of the 6th international conference on cgmp generators, effectors and therapeutic implications. Naunyn. Schmiedebergs Arch. Pharmacol. 387, 707-718 (2014).
55. Chen, Y. et al. Mir-155 regulates differentiation of brown and beige adipocytes via a bistable circuit. Nat. Commun. 4, 1769 (2013).
56. Jennissen, K. et al. A vasp-rac-soluble guanylyl cyclase pathway controls cgmp production in adipocytes. Sci. Signal. 5, ra62 (2012).