Selective inhibition of Hypoxia-inducible factor 1α ameliorates adipose tissue dysfunction

Molecular and Cellular Biology

Volumn 33, Issue 5, 2013, Pages 904-917

  Sun, Kai ^a   Halberg, Nils ^a,d   Khan, Mahmood ^b   Magalang, Ulysses J ^b   Scherer, Philipp E ^a,c  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER   (United States)

^c UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^d ROCKEFELLER UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 [BIS(2 CHLOROETHYL)OXIDOAMINO]PHENYLALANINE; DOXYCYCLINE; HYPOXIA INDUCIBLE FACTOR 1ALPHA;

ADIPOSE TISSUE; ANIMAL EXPERIMENT; ARTICLE; BODY WEIGHT; BROWN ADIPOSE TISSUE; CONTROLLED STUDY; ENERGY EXPENDITURE; FIBROSIS; LIPID DIET; MALE; METABOLIC PARAMETERS; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; WEIGHT GAIN; WHITE ADIPOSE TISSUE;

ADIPOSE TISSUE; ANIMALS; DIET, HIGH-FAT; DIGOXIN; ENERGY METABOLISM; FATTY LIVER; GLUCOSE TOLERANCE TEST; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; LIVER; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MUSTARD COMPOUNDS; MUTATION; OXYGEN; PHENYLPROPIONATES; UP-REGULATION; WEIGHT GAIN;

EID: 84874752310     PISSN: 02707306     EISSN: 10985549     Source Type: Journal    
DOI: 10.1128/MCB.00951-12     Document Type: Article

References (64)

1. Sun K, Kusminski CM, Scherer PE. 2011. Adipose tissue remodeling and obesity. J. Clin. Invest. 121:2094-2101.
2. Arner E, Westermark PO, Spalding KL, Britton T, Ryden M, Frisen J, Bernard S, Arner P. 2010. Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes 59:105-109.
3. Weyer C, Foley JE, Bogardus C, Tataranni PA, Pratley RE. 2000. Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance. Diabetologia 43:1498-1506.
4. Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S, Segawa K, Furukawa S, Tochino Y, Komuro R, Matsuda M, Shimomura I. 2007. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 56:901-911.
5. Ye J. 2009. Emerging role of adipose tissue hypoxia in obesity and insulin resistance. Int. J. Obes. (Lond.) 33:54-66.
6. Yin J, Gao Z, He Q, Zhou D, Guo Z, Ye J. 2009. Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue. Am. J. Physiol. Endocrinol. Metab. 296:E333-E342.
7. Pasarica M, Sereda OR, Redman LM, Albarado DC, Hymel DT, Roan LE, Rood JC, Burk DH, Smith SR. 2009. Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes 58: 718-725.
8. Rausch ME, Weisberg S, Vardhana P, Tortoriello DV. 2008. Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int. J. Obes. (Lond.) 32:451-463.
9. Ye J, Gao Z, Yin J, He Q. 2007. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am. J. Physiol. Endocrinol. Metab. 293: E1118-E1128. doi:10.1152/ajpendo.00435.2007.
10. Halberg N, Khan T, Trujillo ME, Wernstedt-Asterholm I, Attie AD, Sherwani S, Wang ZV, Landskroner-Eiger S, Dineen S, Magalang UJ, Brekken RA, Scherer PE. 2009. Hypoxia-inducible factor 1alpha induces fibrosis and insulin resistance in white adipose tissue. Mol. Cell. Biol. 29:4467-4483.
11. Wang B, Wood IS, Trayhurn P. 2007. Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes. Pflugers Arch. 455:479-492.
12. Semenza GL. 2000. Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit. Rev. Biochem. Mol. Biol. 35:71-103.
13. Rocha S. 2007. Gene regulation under low oxygen: holding your breath for transcription. Trends Biochem. Sci. 32:389-397.
14. Kallio PJ, Wilson WJ, O'Brien S, Makino Y, Poellinger L. 1999. Regulation of the hypoxia-inducible transcription factor 1alpha by the ubiquitin- proteasome pathway. J. Biol. Chem. 274:6519-6525.
15. Bruick RK, McKnight SL. 2001. A conserved family of prolyl-4- hydroxylases that modify HIF. Science 294:1337-1340.
16. Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG, Jr. 2001. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications forO2sensing. Science 292:464-468.
17. Salceda S, Caro J. 1997. Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redoxinduced changes. J. Biol. Chem. 272:22642-22647.
18. Brahimi-Horn MC, Pouyssegur J. 2007. Oxygen, a source of life and stress. FEBS Lett. 581:3582-3591.
19. Semenza GL. 2003. Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer 3:721-732.
20. Khan T, Muise ES, Iyengar P, Wang ZV, Chandalia M, Abate N, Zhang BB, Bonaldo P, Chua S, Scherer PE. 2009. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol. Cell. Biol. 29:1575-1591.
21. Belozerov VE, Van Meir EG. 2005. Hypoxia inducible factor-1: a novel target for cancer therapy. Anticancer Drugs 16:901-909.
22. Belozerov VE, Van Meir EG. 2006. Inhibitors of hypoxia-inducible factor- 1 signaling. Curr. Opin. Investig. Drugs 7:1067-1076.
23. Powis G, Kirkpatrick L. 2004. Hypoxia inducible factor-1alpha as a cancer drug target. Mol. Cancer Ther. 3:647-654.
24. Sun X, Kanwar JR, Leung E, Lehnert K, Wang D, Krissansen GW. 2001. Gene transfer of antisense hypoxia inducible factor-1 alpha enhances the therapeutic efficacy of cancer immunotherapy. Gene Ther. 8:638-645.
25. Welsh SJ, Powis G. 2003. Hypoxia inducible factor as a cancer drug target. Curr. Cancer Drug Targets 3:391-405.
26. Welsh S, Williams R, Kirkpatrick L, Paine-Murrieta G, Powis G. 2004. Antitumor activity and pharmacodynamic properties of PX-478, an inhibitor of hypoxia-inducible factor-1alpha. Mol. Cancer Ther. 3:233-244.
27. Jacoby JJ, Erez B, Korshunova MV, Williams RR, Furutani K, Takahashi O, Kirkpatrick L, Lippman SM, Powis G, O'Reilly MS, Herbst RS. 2010. Treatment with HIF-1alpha antagonist PX-478 inhibits progression and spread of orthotopic human small cell lung cancer and lung adenocarcinoma in mice. J. Thorac. Oncol. 5:940-949.
28. Jordan BF, Black K, Robey IF, Runquist M, Powis G, Gillies RJ. 2005. Metabolite changes in HT-29 xenograft tumors following HIF-1alpha inhibition with PX-478 as studied by MR spectroscopy in vivo and ex vivo. NMR Biomed. 18:430-439.
29. Koh MY, Spivak-Kroizman T, Venturini S, Welsh S, Williams RR, Kirkpatrick DL, Powis G. 2008. Molecular mechanisms for the activity of PX-478, an antitumor inhibitor of the hypoxia-inducible factor-1alpha. Mol. Cancer Ther. 7:90-100.
30. Lee K, Kim HM. 2011. A novel approach to cancer therapy using PX-478 as a HIF-1alpha inhibitor. Arch. Pharm. Res. 34:1583-1585.
31. Palayoor ST, Mitchell JB, Cerna D, Degraff W, John-Aryankalayil M, Coleman CN. 2008. PX-478, an inhibitor of hypoxia-inducible factor- 1alpha, enhances radiosensitivity of prostate carcinoma cells. Int. J. Cancer 123:2430-2437.
32. Schwartz DL, Bankson JA, Lemos R, Jr, Lai SY, Thittai AK, He Y, Hostetter G, Demeure MJ, Von Hoff DD, Powis G. 2010. Radiosensitization and stromal imaging response correlates for the HIF-1 inhibitor PX-478 given with or without chemotherapy in pancreatic cancer. Mol. Cancer Ther. 9:2057-2067.
33. Schwartz DL, Powis G, Thitai-Kumar A, He Y, Bankson J, Williams R, Lemos R, Oh J, Volgin A, Soghomonyan S, Nishii R, Alauddin M, Mukhopadhay U, Peng Z, Bornmann W, Gelovani J. 2009. The selective hypoxia inducible factor-1 inhibitor PX-478 provides in vivo radiosensitization through tumor stromal effects. Mol. Cancer Ther. 8:947-958.
34. Chen J, Zhao S, Nakada K, Kuge Y, Tamaki N, Okada F, Wang J, Shindo M, Higashino F, Takeda K, Asaka M, Katoh H, Sugiyama T, Hosokawa M, Kobayashi M. 2003. Dominant-negative hypoxiainducible factor-1 alpha reduces tumorigenicity of pancreatic cancer cells through the suppression of glucose metabolism. Am. J. Pathol. 162:1283-1291.
35. Halterman MW, Miller CC, Federoff HJ. 1999. Hypoxia-inducible factor-1alpha mediates hypoxia-induced delayed neuronal death that involves p53. J. Neurosci. 19:6818-6824.
36. Kung AL, Wang S, Klco JM, Kaelin WG, Livingston DM. 2000. Suppression of tumor growth through disruption of hypoxia-inducible transcription. Nat. Med. 6:1335-1340.
37. Ryan HE, Poloni M, McNulty W, Elson D, Gassmann M, Arbeit JM, Johnson RS. 2000. Hypoxia-inducible factor-1alpha is a positive factor in solid tumor growth. Cancer Res. 60:4010-4015.
38. Rajala MW, Scherer PE. 2003. Minireview: the adipocyte-at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 144:3765-3773.
39. Wang ZV, Deng Y, Wang QA, Sun K, Scherer PE. 2010. Identification and characterization of a promoter cassette conferring adipocyte-specific gene expression. Endocrinology 151:2933-2939.
40. Sun K, Asterholm IW, Kusminski CM, Bueno AC, Wang ZV, Pollard JW, Brekken RA, Scherer PE. 2012. Dichotomous effects of VEGF-A on adipose tissue dysfunction. Proc. Natl. Acad. Sci. U. S. A. 109:5874-5879.
41. Vikram DS, Zweier JL, Kuppusamy P. 2007. Methods for noninvasive imaging of tissue hypoxia. Antioxid. Redox Signal. 9:1745-1756.
42. Khan M, Kwiatkowski P, Rivera BK, Kuppusamy P. 2010. Oxygen and oxygenation in stem-cell therapy for myocardial infarction. Life Sci. 87: 269-274.
43. Pandian RP, Parinandi NL, Ilangovan G, Zweier JL, Kuppusamy P. 2003. Novel particulate spin probe for targeted determination of oxygen in cells and tissues. Free Radic. Biol. Med. 35:1138-1148.
44. Khan M, Mohan IK, Kutala VK, Kotha SR, Parinandi NL, Hamlin RL, Kuppusamy P. 2009. Sulfaphenazole protects heart against ischemiareperfusion injury and cardiac dysfunction by overexpression of iNOS, leading to enhancement of nitric oxide bioavailability and tissue oxygenation. Antioxid. Redox Signal. 11:725-738.
45. Halberg N, Schraw TD, Wang ZV, Kim JY, Yi J, Hamilton MP, Luby-Phelps K, Scherer PE. 2009. Systemic fate of the adipocyte-derived factor adiponectin. Diabetes 58:1961-1970.
46. Wang B, Wood IS, Trayhurn P. 2008. Hypoxia induces leptin gene expression and secretion in human preadipocytes: differential effects of hypoxia on adipokine expression by preadipocytes. J. Endocrinol. 198: 127-134.
47. Lin S, Thomas TC, Storlien LH, Huang XF. 2000. Development of high fat diet-induced obesity and leptin resistance in C57Bl/6J mice. Int. J. Obes. Relat. Metab. Disord. 24:639-646.
48. Trayhurn P, Wood IS. 2004. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br. J. Nutr. 92:347-355.
49. Jiang C, Qu A, Matsubara T, Chanturiya T, Jou W, Gavrilova O, Shah YM, Gonzalez FJ. 2011. Disruption of hypoxia-inducible factor 1 in adipocytes improves insulin sensitivity and decreases adiposity in high-fat diet-fed mice. Diabetes 60:2484-2495.
50. Krishnan J, Danzer C, Simka T, Ukropec J, Walter KM, Kumpf S, Mirtschink P, Ukropcova B, Gasperikova D, Pedrazzini T, Krek W. 2012. Dietary obesity-associated Hif1alpha activation in adipocytes restricts fatty acid oxidation and energy expenditure via suppression of the Sirt2-NAD+ system. Genes Dev. 26:259-270.
51. Giaccia A, Siim BG, Johnson RS. 2003. HIF-1 as a target for drug development. Nat. Rev. Drug Discov. 2:803-811.
52. Jordan BF, Runquist M, Raghunand N, Baker A, Williams R, Kirkpatrick L, Powis G, Gillies RJ. 2005. Dynamic contrast-enhanced and diffusion MRI show rapid and dramatic changes in tumor microenvironment in response to inhibition of HIF-1alpha using PX-478. Neoplasia 7:475-485.
53. Brennan AM, Mantzoros CS. 2006. Drug insight: the role of leptin in human physiology and pathophysiology-emerging clinical applications. Nat. Clin. Pract. Endocrinol. Metab. 2:318-327.
54. Mason SD, Rundqvist H, Papandreou I, Duh R, McNulty WJ, Howlett RA, Olfert IM, Sundberg CJ, Denko NC, Poellinger L, Johnson RS. 2007. HIF-1alpha in endurance training: suppression of oxidative metabolism. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293:R2059 -R2069. doi:10.1152/ajpregu.00335.2007.
55. Hotamisligil GS. 2006. Inflammation and metabolic disorders. Nature 444:860-867.
56. Yudkin JS. 2003. Adipose tissue, insulin action and vascular disease: inflammatory signals. Int. J. Obes. Relat. Metab. Disord. 27(Suppl 3):S25-S28.
57. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW, Jr. 2003. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112:1796-1808.
58. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. 2003. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112:1821-1830.
59. Aragonés J, Schneider M, Van Geyte K, Fraisl P, Dresselaers T, Mazzone M, Dirkx R, Zacchigna S, Lemieux H, Jeoung NH, Lambrechts D, Bishop T, Lafuste P, Diez-Juan A, Harten SK, Van Noten P, De Bock K, Willam C, Tjwa M, Grosfeld A, Navet R, Moons L, Vandendriessche T, Deroose C, Wijeyekoon B, Nuyts J, Jordan B, Silasi-Mansat R, Lupu F, Dewerchin M, Pugh C, Salmon P, Mortelmans L, Gallez B, Gorus F, Buyse J, Sluse F, Harris RA, Gnaiger E, Hespel P, Van Hecke P, Schuit F, Van Veldhoven P, Ratcliffe P, Baes M, Maxwell P, Carmeliet P. 2008. Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism. Nat. Genet. 40:170-180.
60. Mason SD, Howlett RA, Kim MJ, Olfert IM, Hogan MC, McNulty W, Hickey RP, Wagner PD, Kahn CR, Giordano FJ, Johnson RS. 2004. Loss of skeletal muscle HIF-1alpha results in altered exercise endurance. PLoS Biol. 2:e288.
61. Tajima T, Goda N, Fujiki N, Hishiki T, Nishiyama Y, Senoo-Matsuda N, Shimazu M, Soga T, Yoshimura Y, Johnson RS, Suematsu M. 2009. HIF-1alpha is necessary to support gluconeogenesis during liver regeneration. Biochem. Biophys. Res. Commun. 387:789-794.
62. Kabon B, Nagele A, Reddy D, Eagon C, Fleshman JW, Sessler DI, Kurz A. 2004. Obesity decreases perioperative tissue oxygenation. Anesthesiology 100:274-280.
63. Virtanen KA, Lonnroth P, Parkkola R, Peltoniemi P, Asola M, Viljanen T, Tolvanen T, Knuuti J, Ronnemaa T, Huupponen R, Nuutila P. 2002. Glucose uptake and perfusion in subcutaneous and visceral adipose tissue during insulin stimulation in nonobese and obese humans. J. Clin. Endocrinol. Metab. 87:3902-3910.
64. Abrosini G, Nath AK, Sierra-Honigmann MR, Flores-Riveros J. 2002. Transcriptional activation of the human leptin gene in response to hypoxia: involvement of hypoxia-inducible factor 1. J. Biol. Chem. 277: 34601-34609.