This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bing, C. Articles by Williams, G. Search for Related Content PubMed PubMed Citation Articles by Bing, C. Articles by Williams, G.

Increased Gene Expression of Brown Fat Uncoupling Protein (UCP)1 and Skeletal Muscle UCP2 and UCP3 in MAC16-induced Cancer Cachexia¹

Diabetes and Endocrinology Research Group, Department of Medicine, University of Liverpool, Liverpool L69 3GA [C. B., M. B., P. K., P. C., G. W.], and Pharmaceutical Sciences Research Institute, Aston University, Birmingham B4 7ET [M. J. T.], United Kingdom

Weight loss in cancer cachexia is attributable to decreased food intake and/or enhanced energy expenditure. We investigated the roles of the uncoupling proteins (UCPs) UCP1, -2, and -3 in a murine model of cachexia, the MAC16 adenocarcinoma. Weight fell to 24% below that of non-tumor-bearing controls (P < 0.01) 18 days after MAC16 inoculation, with significant reductions in fat-pad mass (-67%; P < 0.01) and muscle mass (-20%; P < 0.01). Food intake was 26–60% lower (P < 0.01) than in controls on days 17–18. Non-tumor-bearing mice, pair-fed to match MAC16-induced hypophagia, showed less weight loss (10% below controls, P < 0.01; 16% above MAC-16, P < 0.01) and smaller decreases in fat-pad mass (21% below controls, P < 0.01). Core temperature in MAC16 mice was significantly lower (-2.4°C, P < 0.01) than in controls, and pair-feeding had no effect.

MAC16 mice showed significantly higher UCP1 mRNA levels in brown adipose tissue (BAT) than in controls (+63%, P < 0.01), and pair-feeding had no effect. UCP2 and -3 expression in BAT did not differ significantly between groups. By contrast, UCP2 mRNA levels in skeletal muscle were comparably increased in both MAC16 and pair-fed groups (respectively, 183 and 163% above controls; both, P < 0.05), with no significant difference between these two groups. Similarly, UCP3 mRNA was significantly higher than controls in both MAC16 (+163%, P < 0.05) and pair-fed (+253%, P < 0.01) groups, with no significant difference between the two experimental groups.

Overexpression of UCP1 in BAT in MAC16-bearing mice may be an adaptive response to hypothermia, which is apparently induced by tumor products; increased thermogenesis in BAT could increase total energy expenditure and, thus, contribute to tissue wasting. Increased UCP2 and -3 expression in muscle are both attributable to reduced food intake and may be involved in lipid utilization during lipolysis in MAC16-induced cachexia.

This article has been cited by other articles:

				D. J. Mazzatti, M. A. Smith, R. C. Oita, F.-L. Lim, A. J. White, and M. B. Reid Muscle unloading-induced metabolic remodeling is associated with acute alterations in PPAR{delta} and UCP-3 expression Physiol Genomics, July 9, 2008; 34(2): 149 - 161. [Abstract] [Full Text] [PDF]

				W. W. Cheung, H.-J. Kuo, S. Markison, C. Chen, A. C. Foster, D. L. Marks, and R. H. Mak Peripheral Administration of the Melanocortin-4 Receptor Antagonist NBI-12i Ameliorates Uremia-Associated Cachexia in Mice J. Am. Soc. Nephrol., September 1, 2007; 18(9): 2517 - 2524. [Abstract] [Full Text] [PDF]

				M. J. Delano and L. L. Moldawer The Origins of Cachexia in Acute and Chronic Inflammatory Diseases Nutr Clin Pract, February 1, 2006; 21(1): 68 - 81. [Abstract] [Full Text] [PDF]

				M. J. Tisdale Molecular Pathways Leading to Cancer Cachexia Physiology, October 1, 2005; 20(5): 340 - 348. [Abstract] [Full Text] [PDF]

				M. E. Martignoni, P. Kunze, W. Hildebrandt, B. Kunzli, P. Berberat, T. Giese, O. Kloters, J. Hammer, M. W. Buchler, N. A. Giese, et al. Role of Mononuclear Cells and Inflammatory Cytokines in Pancreatic Cancer-Related Cachexia Clin. Cancer Res., August 15, 2005; 11(16): 5802 - 5808. [Abstract] [Full Text] [PDF]

				D. H. Esper and W. A. Harb The Cancer Cachexia Syndrome: A Review of Metabolic and Clinical Manifestations Nutr Clin Pract, August 1, 2005; 20(4): 369 - 376. [Abstract] [Full Text] [PDF]

				C. Bing, Y. Bao, J. Jenkins, P. Sanders, M. Manieri, S. Cinti, M. J. Tisdale, and P. Trayhurn Zinc-{alpha}2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia PNAS, February 24, 2004; 101(8): 2500 - 2505. [Abstract] [Full Text] [PDF]

				G. Argyropoulos and M.-E. Harper Molecular Biology of Thermoregulation: Invited Review: Uncoupling proteins and thermoregulation J Appl Physiol, May 1, 2002; 92(5): 2187 - 2198. [Abstract] [Full Text] [PDF]

				J. Himms-Hagen and M.-E. Harper Physiological Role of UCP3 May Be Export of Fatty Acids from Mitochondria When Fatty Acid Oxidation Predominates: An Hypothesis Experimental Biology and Medicine, February 1, 2001; 226(2): 78 - 84. [Abstract] [Full Text]