Increased gene expression of brown fat uncoupling protein (UCP)1 and skeletal muscle UCP2 and UCP3 in MAC16-induced cancer cachexia

Weight loss in cancer cachexia is attributable to decreased food intake and /or enhanced energy expenditure. We investigated the roles of the uncouplin g 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 control s (P < 0.01) 18 days after MAC16 inoculation, with significant reductions i n fat-pad mass (-67%; P < 0.01) and muscle mass (-20%; P < 0.01). Food inta ke was 26-60% lower (P < 0.01) than in controls on days 17-18, Non-tumor-be aring 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 c ontrols, and pair-feeding had no effect. MAC16 mice showed significantly higher UCP1 mRNA levels in brown adipose ti ssue (BAT) than in controls (+63%, P < 0.01), and pair-feeding had no effec t, UCP2 and -3 expression in BAT did not differ significantly between group s. By contrast, UCP2 mRNA levels in skeletal muscle were comparably increas ed in both MAC16 and pair-fed groups (respectively, 183 and 163% above cont rols; both, P < 0.05), with no significant difference between these two gro ups. Similarly, UCP3 mRNA was significantly higher than controls in both MA C16 (+163%, P < 0.05) and pair-fed (+253%,P < 0.01) groups, with no signifi cant difference between the two experimental groups, Overexpression of UCP1 in BAT in MAC16-bearing mice may be an adaptive resp onse to hypothermia, which is apparently induced by tumor products; increas ed thermogenesis in BAT could increase total energy expenditure and, thus, contribute to tissue wasting. Increased UCP2 and -3 expression in muscle ar e both attributable to reduced Food intake and may be involved in lipid uti lization during Lipolysis in MAC16-induced cachexia.