Subscribe to RSS
DOI: 10.1055/s-2002-38239
© Georg Thieme Verlag Stuttgart · New York
Weight Loss in Tumour-Bearing Mice Is Not Associated with Changes in Resistin Gene Expression in White Adipose Tissue
Publication History
Received 23 May 2002
Accepted after revision 31 July 2002
Publication Date:
27 March 2003 (online)
![](https://www.thieme-connect.de/media/hmr/20021112/lookinside/thumbnails/10.1055-s-2002-38239-1.jpg)
Abstract
Resistin, a product of white adipose tissue, is postulated to induce insulin resistance in obesity and regulate adipocyte differentiation. The aim of this study was to examine resistin gene expression in adipose tissue from mice bearing the MAC16 adenocarcinoma, which induces cancer cachexia with marked wasting of adipose tissue and skeletal muscle mass. MAC16-bearing mice lost weight progressively over the period following tumour transplantation, while the weight of control mice remained stable. Leptin mRNA in gonadal fat was 50 % lower in MAC16 mice than in controls (p < 0.05). Plasma insulin concentrations were also significantly lower in the MAC16 group (p < 0.05). However, resistin mRNA level in gonadal fat in MAC16 mice was similar to controls (94 % of controls). Thus, despite severe weight loss and significant falls in leptin expression and insulin concentration, resistin gene expression appears unchanged in white adipose tissue of mice with MAC16 tumour. Maintenance of resistin production may help inhibit the formation of new adipocytes in cancer cachexia.
Key words
Resistin - Cancer Cachexia - Leptin - Insulin - Adipose Tissue
References
- 1 Tisdale M J. Biology of cachexia. J Natl Cancer Inst. 1997; 89 1763-1773
- 2 Tisdale M J. Cancer anorexia and cachexia. Nutrition. 2001; 17 438-442
- 3 Okamoto Y, Arita Y, Nishida M, Muraguchi M, Ouchi N, Takahashi M, Igura T, Inui Y, Kihara S, Nakamura T, Yamashita S, Miyagawa J, Funahashi T, Matsuzawa Y. An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res. 2000; 32 47-50
- 4 Langin D, Lucas S, Lafontan M. Millennium fat-cell lipolysis reveals unsuspected novel tracks. Horm Metab Res. 2000; 32 443-452
- 5 Frühbeck G, Gómez-Ambrosi J, Muruzábal F J, Burrell M A. The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol Endocrinol Metab. 2001; 280 E827-847
- 6 Steppan C M, Bailey S T, Bhat S, Brown E J, Banerjee R R, Wright C M, Patel H R, Ahima R S, Lazar M A. The hormone resistin links obesity to diabetes. Nature. 2001; 409 307-312
- 7 Way J M, Görgün C Z, Tong Q, Uysal K T, Brown K K, Harrington W W, Oliver W R, Willson T M, Kliewer S A, Hotamisligil G S. Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor g agonists. J Biol Chem. 2001; 276 25 651-25 653
- 8 Le Lay S, Boucher J, Rey A, Castan-Laurell I, Krief S, Ferré P, Valet P, Dugail I. Decreased resistin expression in mice with different sensitivities to a high-fat diet. Biochem Biophys Res Commun. 2001; 289 564-567
- 9 Moore G B, Chapman H, Holder J C, Lister C A, Piercy V, Smith S A, Clapham J C. Differential regulation of adipocytokine mRNAs by rosiglitazone in db/db mice. Biochem Biophys Res Commun. 2001; 286 735-741
- 10 Steppan C M, Lazar M A. Resistin and obesity-associated insulin resistance. Trends Endocrinol Metab. 2002; 13 18-23
- 11 Levy J R, Davenport B, Clore J N, Stevens W. Lipid metabolism and resistin gene expression in insulin-resistant Fischer 344 rats. Am J Physiol Endocrinol Metab. 2002; 282 E626-633
- 12 Kim K H, Lee K, Moon Y S, Sul H S. A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem. 2001; 276 11 252-11 256
- 13 Lundholm K, Holm G, Schersten T. Insulin resistance in patients with cancer. Cancer Res. 1978; 38 4665-4670
- 14 Copeland G P, Leinster S J, Davis J C, Hipkin L J. Insulin resistance in patients with colorectal cancer. Br J Surg. 1987; 74 1031-1035
- 15 Yoshikawa T, Noguchi Y, Satoh S. Inhibition of IRS-1 phosphorylation and the alterations of GLUT4 in isolated adipocytes from cachectic tumor-bearing rats. Biochem Biophys Res Commun. 1999; 256 676-681
- 16 Beck S A, Tisdale M J. Production of lipolytic and proteolytic factors by a murine tumor-producing cachexia in the host. Cancer Res. 1987; 47 5919-5923
- 17 Trayhurn P, Duncan J S, Nestor A, Thomas M E, Rayner D V. Chemiluminescent detection of mRNAs on northern blots with digoxigenin end-labeled oligonucleotides. Anal Biochem. 1994; 222 224-230
- 18 Haugen F, Jørgensen A, Drevon C A, Trayhurn P. Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes. FEBS Lett. 2001; 507 105-108
- 19 Trayhurn P, Duncan J S, Rayner D V. Acute cold-induced suppression of ob (obese) gene expression in white adipose tissue of mice: mediation by the sympathetic system. Biochem J. 1995; 311 729-733
- 20 Bibby M C, Double J A, Ali S A, Fearon K C, Brennan R A, Tisdale M J. Characterization of a transplantable adenocarcinoma of the mouse colon producing cachexia in recipient animals. J Natl Cancer Inst. 1987; 78 539-546
- 21 Bing C, Brown M, King P, Collins P, Tisdale M J, Williams G. Increased gene expression of brown fat uncoupling protein (UCP)1 and skeletal muscle UCP2 and UCP3 in MAC16-induced cancer cachexia. Cancer Res. 2000; 60 2405-2410
- 22 Bing C, Taylor S, Tisdale M J, Williams G. Cachexia in MAC16 adenocarcinoma: suppression of hunger despite normal regulation of leptin, insulin and hypothalamic neuropeptide Y. J Neurochem. 2001; 79 1004-1012
- 23 Bing C, Russell S T, Beckett E E, Collins P, Taylor S, Barraclough R, Tisdale M J, Williams G. Expression of uncoupling proteins-1, -2 and -3 mRNA is induced by an adenocarcinoma-derived lipid-mobilizing factor. Br J Cancer. 2002; 86 612-618
- 24 Todorov P, Cariuk P, McDevitt T, Coles B, Fearon K, Tisdale M. Characterization of a cancer cachectic factor. Nature. 1996; 379 739-742
- 25 Todorov P T, McDevitt T M, Meyer D J, Ueyama H, Ohkubo I, Tisdale M J. Purification and characterization of a tumor lipid-mobilizing factor. Cancer Res. 1998; 58 2353-2358
- 26 López-Soriano J, Carbó N, Tessitore L, López-Soriano F J, Argilés J M. Leptin and tumor growth in rats. Int J Cancer. 1999; 81 726-729
- 27 Wallace A M, Sattar N, McMillan D C. Effect of weight loss and the inflammatory response on leptin concentrations in gastrointestinal cancer patients. Clin Cancer Res. 1998; 4 2977-2979
Dr. J. Gómez-Ambrosi
Metabolic Research Laboratory · Clínica Universitaria de Navarra · University of Navarra · Edificio CIFA
Irunlarrea 1 · 31008 Pamplona · Spain·
Phone: + 34 (948) 425600 ext. 6567
Fax: + 34 (948) 425652
Email: jagomez@unav.es