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
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Email: jagomez@unav.es