Metabolic Consequences of High-Fat Diet Are Attenuated by Suppression of HIF-1 alpha

Imagem de Miniatura
Arquivos
art_DRAGER_Metabolic_Consequences_of_High_Fat_Diet_Are_Attenuated_2012.PDF (729.97 KB)
Citações na Scopus
55
Tipo de produção
article
Data de publicação
2012
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
PUBLIC LIBRARY SCIENCE
Autores
SHIN, Mi-Kyung
YAO, Qiaoling
BEVANS-FONTI, Shannon
YOO, Doo-Young
JUN, Jonathan C.
AJA, Susan
BHANOT, Sanjay
POLOTSKY, Vsevolod Y.
Citação
PLOS ONE, v.7, n.10, article ID e46562, 10p, 2012
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Obesity is associated with tissue hypoxia and the up-regulation of hypoxia inducible factor 1 alpha (HIF-1 alpha). Prior studies in transgenic mice have shown that HIF-1 alpha plays a role in the metabolic dysfunction associated with obesity. Therefore, we hypothesized that, after the development of diet-induced obesity (DIO), metabolic function could be improved by administration of HIF-1 alpha antisense oligonucleotides (ASO). DIO mice were treated with HIF-1 alpha ASO or with control ASO for 8 weeks and compared with an untreated group. We found that HIF-1 alpha ASO markedly suppressed Hif-1 alpha gene expression in adipose tissue and the liver. HIF-1 alpha ASO administration induced weight loss. Final body weight was 41.6 +/- 1.4 g in the HIF-1 alpha ASO group vs 46.7 +/- 0.9 g in the control ASO group and 47.9 +/- 0.8 g in untreated mice (p<0.001). HIF-1 alpha ASO increased energy expenditure (13.3 +/- 0.6 vs 12 +/- 0.1 and 11.9 +/- 0.4 kcal/kg/hr, respectively, p<0.001) and decreased the respiratory exchange ratio (0.71 +/- 0.01 vs 0.75 +/- 0.01 and 0.76 +/- 0.01, respectively, p<0.001), which suggested switching metabolism to fat oxidation. In contrast, HIF-1a ASO had no effect on food intake or activity. HIF-1 alpha ASO treatment decreased fasting blood glucose (195.5 +/- 8.4 mg/dl vs 239 +/- 7.8 mg/dl in the control ASO group and 222 +/- 8.2 mg/dl in untreated mice, p<0.01), plasma insulin, hepatic glucose output, and liver fat content. These findings demonstrate that the metabolic consequences of DIO are attenuated by HIF-1 alpha ASO treatment.
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/1467
Referências
  1. Bennett CF, 2010, ANNU REV PHARMACOL, V50, P259, DOI 10.1146/annurev.pharmtox.010909.105654
  2. Brownsey RW, 2006, BIOCHEM SOC T, V34, P223
  3. Burgueno AL, 2012, CLIN SCI LOND
  4. Cai DS, 2005, NAT MED, V11, P183, DOI 10.1038/nm1166
  5. Cannon B, 2004, PHYSIOL REV, V84, P277, DOI 10.1152/physrev.00015.2003
  6. Carabelli J, 2011, J CELL MOL MED, V15, P1329, DOI 10.1111/j.1582-4934.2010.01128.x
  7. Collins S, 2010, INT J OBESITY, V34, pS28, DOI 10.1038/ijo.2010.180
  8. Delarue J, 2007, CURR OPIN CLIN NUTR, V10, P142, DOI 10.1097/MCO.0b013e328042ba90
  9. Drager LF, 2011, OBESITY, V19, P2167, DOI 10.1038/oby.2011.240
  10. Enerback S, 2010, INT J OBESITY, V34, pS43, DOI 10.1038/ijo.2010.183
  11. Fleischmann E, 2005, OBES SURG, V15, P813, DOI 10.1381/0960892054222867
  12. Flowers MT, 2008, CURR OPIN LIPIDOL, V19, P248, DOI 10.1097/MOL.0b013e3282f9b54d
  13. Fromme T, 2011, AM J PHYSIOL-REG I, V300, pR1, DOI 10.1152/ajpregu.00411.2010
  14. Halberg N, 2009, MOL CELL BIOL, V29, P4467, DOI 10.1128/MCB.00192-09
  15. Iiyori N, 2007, AM J RESP CRIT CARE, V175, P851, DOI 10.1164/rccm.200610-1527OC
  16. Iyer NV, 1998, GENE DEV, V12, P149, DOI 10.1101/gad.12.2.149
  17. Jiang CT, 2011, DIABETES, V60, P2484, DOI 10.2337/db11-0174
  18. Jiang GQ, 2005, J CLIN INVEST, V115, P1030, DOI 10.1172/JCI200523962
  19. Kaidanovich Oksana, 2002, Expert Opin Ther Targets, V6, P555
  20. Kim JK, 2000, J CLIN INVEST, V105, P1791, DOI 10.1172/JCI8305
  21. Kozak LP, 2008, INT J OBESITY, V32, pS32, DOI 10.1038/ijo.2008.236
  22. Krishnan J, 2012, GENE DEV, V26, P259, DOI 10.1101/gad.180406.111
  23. Li JG, 2005, J APPL PHYSIOL, V99, P1643, DOI 10.1152/japplphysiol.00522.2005
  24. Li JG, 2006, PHYSIOL GENOMICS, V25, P450, DOI 10.1152/physiolgenomics.00293.2005
  25. Li JG, 2007, J APPL PHYSIOL, V102, P557, DOI 10.1152/japplphysiol.01081.2006
  26. Li JG, 2005, CIRC RES, V97, P698, DOI 10.1161/01.RES.000018379.60089.a9
  27. Li JG, 2007, PHYSIOL GENOMICS, V31, P273, DOI 10.1152/physiolgenomics.00082.2007
  28. Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262
  29. Lusk G, 1928, ELEMENTS SCI NUTR
  30. McKay RA, 1999, J BIOL CHEM, V274, P1715, DOI 10.1074/jbc.274.3.1715
  31. Nath B, 2011, HEPATOLOGY, V53, P1526, DOI 10.1002/hep.24256
  32. Neuschwander-Tetri BA, 2010, HEPATOLOGY, V52, P774, DOI 10.1002/hep.23719
  33. Ochiai D, 2011, BIOCHEM BIOPH RES CO, V415, P445, DOI 10.1016/j.bbrc.2011.10.089
  34. Pasarica M, 2009, DIABETES, V58, P718, DOI 10.2337/db08-1098
  35. Paton CM, 2009, AM J PHYSIOL-ENDOC M, V297, pE28, DOI 10.1152/ajpendo.90897.2008
  36. Polotsky VY, 2003, J PHYSIOL-LONDON, V552, P253, DOI 10.1113/jphysiol.2003.048173
  37. Reinke C, 2011, J APPL PHYSIOL, V111, P881, DOI 10.1152/japplphysiol.00492.2011
  38. Robson-Doucette CA, 2011, DIABETES, V60, P2710, DOI 10.2337/db11-0132
  39. Satterfield MC, 2011, FRONT BIOSCI-LANDMRK, V16, P1589, DOI 10.2741/3807
  40. Schmittgen TD, 2008, NAT PROTOC, V3, P1101, DOI 10.1038/nprot.2008.73
  41. SEMENZA GL, 1994, J BIOL CHEM, V269, P23757
  42. Semenza G.L., 2007, SCI STKE, pcm8
  43. Semenza GL, 2007, SCIENCE, V318, P62, DOI 10.1126/science.1147949
  44. Semenza GL, 2009, PHYSIOLOGY, V24, P97, DOI 10.1152/physiol.00045.2008
  45. Tajima T, 2009, BIOCHEM BIOPH RES CO, V387, P789, DOI 10.1016/j.bbrc.2009.07.115
  46. Unger RH, 2010, BBA-MOL CELL BIOL L, V1801, P209, DOI 10.1016/j.bbalip.2009.10.006
  47. Unger RH, 2002, ANNU REV MED, V53, P319, DOI 10.1146/annurev.med.53.082901.104057
  48. Walston J, 2008, J GERONTOL A-BIOL, V63, P391
  49. Winzell MS, 2004, DIABETES, V53, pS215, DOI 10.2337/diabetes.53.suppl_3.S215
  50. Wood IS, 2009, P NUTR SOC, V68, P370, DOI 10.1017/S0029665109990206
  51. Ye J, 2009, INT J OBESITY, V33, P54, DOI 10.1038/ijo.2008.229
  52. Ye JP, 2007, AM J PHYSIOL-ENDOC M, V293, pE1118, DOI 10.1152/ajpendo.00435.2007
  53. Yin J, 2009, AM J PHYSIOL-ENDOC M, V296, pE333, DOI 10.1152/ajpendo.90760.2008
  54. Zhang XM, 2010, J BIOL CHEM, V285, P32869, DOI 10.1074/jbc.M110.135509

Coleções
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/09