Evaluation of adipose tissue distribution in obese fa/fa Zucker rats by in vivo MR imaging: effects of peroxisome proliferator-activated receptor agonists

  • R. Fissoune
  • N. Pellet
  • L. Chaabane
  • F. Contard
  • D. Guerrier
  • A. Briguet
Research Article

Abstract

High-resolution MRI of obese (fa/fa) Zucker rats was investigated to characterize and assess in vivo adipose tissue distribution. Thirty animals were gavaged with a placebo, a PPARγ activator (pioglitazone), or a dual PPARα γ activator (LM 4156). At day 15, T1-weighted images were acquired in vivo using a 2TMRI system with a high in-plane spatial resolution (254 μm). Fat volumes of selected territories were measured by image segmentation, and the retroperitoneal fat was weighed post-mortem. Body-weight gain was significant with pioglitazone (101.8±5.9 g, p<0.01 vs. placebo). The good quality of MR images allowed the delimitation and quantification of different fat territories. In response to pioglitazone, the retroperitoneal fat was more important compared to placebo (+23%, p<0.01) while subcutaneous fat was not different. No significant effects were observed with LM 4156. In vivo measurements of fat volumes were strongly correlated with ex vivo tissue weights (r=0.91). High-resolution MRI provides an in vivo measurement of adipose tissue distribution in obese Zucker rats. Specific fat depots of regions that were particularly involved in drug response were determined in vivo. Fat remodeling was observed with pioglitazone but not with a dual PPARα γ activator (LM 4156).

Keywords

Magnetic resonance imaging (MRI) Fat remodeling Diabetes Adipose tissues Peroxisome proliferator-activated receptor (PPAR) 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kirchengast S, Huber J (2004) Body composition characteristics and fat distribution patterns in young infertile women. Fertil Steril 81:539–544CrossRefPubMedGoogle Scholar
  2. 2.
    Chan DC, Watts GF, Sussekov AV, Barrett PHR, Yang Z, Hua J, Song S (2004) Adipose tissue compartments and insulin resistance in overweight–obese Caucasian men. Diabetes Res Clin Pract 63:77–85CrossRefPubMedGoogle Scholar
  3. 3.
    Changani KK, Nicholson A, White A, Latchman JK, Reid DG, Clapham JC (2003) A longitudinal magnetic resonance imaging (MRI) study of differences in abdominal fat distribution between normal mice, and lean overexpressors of mitochondrial uncoupling protein-3 (UCP-3). Diabetes Obes Metab 5:99–105CrossRefPubMedGoogle Scholar
  4. 4.
    Tang H, Vasselli JR, Wu EX (2002) High-resolution magnetic resonance imaging tracks changes in organ and tissue mass in obese and aging rats. Am J Physiol Regul Comp Physiol 282:R890–R899Google Scholar
  5. 5.
    Kenneth JE (2000) Human body composition: in vivo methods. Physiol Rev 2:649–680Google Scholar
  6. 6.
    Yoshizumi T, Nakamura T, Yamane M, Islam AH, Menju M, Yamasaki K, Arai T, Kotani K, Funahashi T, Yamashita S, Matsuzawa Y (1999) Abdominal fat: standardized technique for measurement at CT. Radiology 211:283–286PubMedGoogle Scholar
  7. 7.
    Keller C, Chintapalli K, Lancaster J (1999) Correlation of anthropometry with CT in mexican-american women. Res Nurs Health 22:145–153PubMedGoogle Scholar
  8. 8.
    Lemieux S, Lesage M, Bergeron J, Prud’homme D, Després (1999) Comparison of two techniques for measurement of visceral adipose tissue cross-sectional areas by computed tomography. Am J Hum Biol 11:61–68PubMedGoogle Scholar
  9. 9.
    Paradisi G, Smith L, Burtner C, Leaming R, Gravey WT, Hook G, Johnson A, Cronin J, Steinberg HO, Baron AD (1999) Dual energy X-ray absorptiometry assessment of fat mass distribution and its association with the insulin resistance syndrome. Diabetes Care 22:1310–1317PubMedGoogle Scholar
  10. 10.
    Ross R (2003) Advances in the application of imaging methods in applied and clinical physiology. Acta Diabetol 40:S45–S50CrossRefPubMedGoogle Scholar
  11. 11.
    Shen W, Wang Z, Punyanita M, Lei J, Sinav A, Kral JG, Imielinska C, Ross R, Heymsfield SB (2003) Adipose tissue quantification by imaging methods: a proposed classification. Obes Res 11:5–16CrossRefPubMedGoogle Scholar
  12. 12.
    Ross R (1996) Magnetic resonance imaging provides new insights into the characterization of adipose and lean tissue distribution. Can J Physiol Pharmacol 74:778–785CrossRefPubMedGoogle Scholar
  13. 13.
    Thomas EL, Saeed N, Hajnal JV, Brynes A, Goldstone AP, Frost G, Bell JD (1998) Magnetic resonance imaging of total body fat. J Appl Physiol 85:1778–1785PubMedGoogle Scholar
  14. 14.
    Gronemeyer SA, Steen RG, Kauffman WM, Reddick WE, Glass JO (2000) Fat adipose tissue (FAT) assessment by MRI. Magn Reson Imaging 18:815–818CrossRefPubMedGoogle Scholar
  15. 15.
    Abate N, Burns D, Peshock RM, Garg A, Grundy SM (1994) Estimation of adipose tissue mass by magnetic resonance imaging: validation against dissection in human cadavers. J Lipid Res 35:1490–1496PubMedGoogle Scholar
  16. 16.
    Ishikawa M, Koga K (1998) Measurement of abdominal fat by magnetic resonance imaging of Oletf rats, an animal model of NIDDM. Magn Reson Imaging 16:45–53CrossRefPubMedGoogle Scholar
  17. 17.
    Tintera J, Harantova P, Suchanek P, Dvorakova A, Adamova M, Hajek M, Poledne R (2004) Quantification of intra-abdominal fat during controlled weight reduction: assessment using the water-suppressed breath-hold MRI technique. Physiol Res 53:229–234PubMedGoogle Scholar
  18. 18.
    Olefsky JM, Saltiel AR (2000) PPAR gamma and the treatment of insulin resistance. Trends Endocrinol Metab 11:362–368CrossRefPubMedGoogle Scholar
  19. 19.
    Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA (1995) An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem 270:12953–12956CrossRefPubMedGoogle Scholar
  20. 20.
    Mori Y, Murakawa Y, Okada K, Horikoshi H, Yokoyama J, Tajima N, Ikeda Y (1999) Effect of troglitazone on body fat distribution in type 2 diabetic patients. Diabetes Care 22:908–912PubMedGoogle Scholar
  21. 21.
    Chaput E, Saladin R, Silvestre M, Edgar AD (2000) Fenofibrate and rosiglitazone lower serum triglycerides with opposing effects on body weight. Biochem Biophys Res Commun 271:445–450PubMedGoogle Scholar
  22. 22.
    Chevreuil O, Contard F, Guerrier D (2003) LM 4156, a novel, balanced activator of PPAR alpha and gamma improves dyslipidemia in fa/fa Zucker Rats. Diabetes 52(Suppl. 6):A114Google Scholar
  23. 23.
    Contard F, Chevreuil O, Guerrier D (2003) LM 4156, a novel, balanced PPAR α and γ activator decreases hypertriglyceridaemia without effects on body weight and adipose tissue in fa/fa Zucker Rats. Diabetes 52(Suppl. 1):A444Google Scholar
  24. 24.
    Kelly IE, Han TS, Walsh K, Lean MEJ (1999) Effects of thiazolinedione compound on body fat and fat distribution of patients with type 2 diabetes. Diabetes Care 22:288–293PubMedGoogle Scholar
  25. 25.
    De Souza CJ, Eckhardt M, Gagen K, Dong M, Chen W, Laurent D, Burkey BF (2001) effects of pioglitazone on adipose tissue remodelling within the setting of obesity and insulin resistance. Diabetes 50:1863–1871PubMedGoogle Scholar
  26. 26.
    Sinha R, Dufour S, Petersen KF, LeBon V, Enoksson S, et al. (2002) Assessment of skeletal muscle triglyceride content by 1H nuclear magnetic resonance spectroscopy in lean and obese adolescents. Diabetes 51:1022–1027PubMedGoogle Scholar
  27. 27.
    Jucker BM, Schaeffer TR, Haimbach RE, Mayer ME, Ohlstein EH, Smith SA, Cobitz AR, Susanta K Sarkar (2003) Reduction of intramyocellular lipid following short-term rosiglitazone treatment in Zucker fatty rats: an in vivo nuclear magnetic resonance study. Metabolism 52:218–225CrossRefPubMedGoogle Scholar
  28. 28.
    Hallakou S, Doare L, Foufelle F, Kergoat M, Guerre-Millo M, Berthault MF, Dugail I, Morin J, Auwerx J, Ferre P (1997) Pioglitazone induces in vivo adipocyte differentiation in the obese Zucker fa/fa rat. Diabetes 46:1393–1399PubMedGoogle Scholar
  29. 29.
    Lebovitz HE (1997) Differentiating members of the thiazolidinedione class: a focus on safety. Diabetes Metab Res Rev 18(Suppl. 2):S23–S29Google Scholar
  30. 30.
    Tordjman J, Chauvet G, Quette J, Beale EG, Forest C, Antoine B (2003) Thiazolidinediones block fatty acid release by inducing glyceroneogenesis in fat cells. The J Biol Chem 278:18785–18790CrossRefGoogle Scholar
  31. 31.
    Lebovitz HE (2003) The relationship of obesity to the metabolic syndrome. Int J Clin Pract Suppl 134:18–27PubMedGoogle Scholar
  32. 32.
    Wajchenberg BL (2000) Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21(6):697–738PubMedGoogle Scholar
  33. 33.
    Oakes ND, Thalen PG, Jacinto SM, Ljung B (2001) Thiazolidinediones increase plasma adipose tissue FFA exchange capacity and enhance insulin-mediated control of systemic FFA availability. Diabetes 50:1158–1165PubMedGoogle Scholar
  34. 34.
    Lebovitz HE (1997) Differentiating members of the thiazolidinedione class: a focus on safety. Diabetes Metab Res Rev 18(Suppl. 2):S23–S29Google Scholar

Copyright information

© ESMRMB 2004

Authors and Affiliations

  • R. Fissoune
    • 1
  • N. Pellet
    • 1
  • L. Chaabane
    • 1
  • F. Contard
    • 1
  • D. Guerrier
    • 2
  • A. Briguet
    • 2
  1. 1.Laboratoire de RMNCNRS UMR 5012, CPE- UCB LYON IVilleurbanneFrance
  2. 2.Animal Physiopathology DepartmentMERCK SantéLyonFrance

Personalised recommendations