title: Increased gene expression of brown fat uncoupling protein (UCP)1 and skeletal muscle UCP2 and UCP3 in MAC16-induced cancer cachexia.
abstract: 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) UCPI, -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 degrees 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.
authors.affiliation: Department of Medicine, University of Liverpool, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Bing
authors.forename: M
authors.initials: M
authors.lastname: Brown
authors.forename: P
authors.initials: P
authors.lastname: King
authors.forename: P
authors.initials: P
authors.lastname: Collins
authors.forename: M J
authors.initials: MJ
authors.lastname: Tisdale
authors.forename: G
authors.initials: G
authors.lastname: Williams
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D001831:Body Temperature; D001835:Body Weight; D002100:Cachexia / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D004435:Eating; D005260:Female; D015870:Gene Expression; D007473:Ion Channels; D020738:Leptin / Q000097:blood; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D026901:Membrane Transport Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012337:RNA, Ribosomal, 18S / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
chemical_list: D002352:Carrier Proteins; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D014409:Tumor Necrosis Factor-alpha; C000604372:Ucp1 protein, mouse; C000604390:Ucp2 protein, mouse; C000604393:Ucp3 protein, mouse; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3