Alterations of lipid and cholesterol metabolism in cachectic tumor bearingrats are prevented by insulin

The ascites hepatoma Yoshida AH130 causes in the host a rapid and progressi ve body weight loss, associated with reduced food intake, and protein and l ipid hypercatabolism. Because insulin regulates glucose as well as lipid an d protein metabolism, we suggest that the observed alterations are at least in part secondary to hypoinsulinemia and/or to the increase of counterregu latory hormones in AH130-bearing rats. To verify this hypothesis, controls with free access to food (n = 4), controls with free access to food plus in sulin (107 mu mol.kg body wt(-1).d(-1)) (n = 4), controls pair-fed to the t umor-bearing rats (n = 4), pair-fed controls treated with insulin (n = 4), tumor hosts (n = 9), and tumor hosts treated with insulin (n = 6) were used . The Yoshida ascites hepatoma cells (similar to 10(8) cells/rat) were inoc ulated intraperitoneally. Daily food intake and body weight were measured; insulin was injected starting the day of tumor implantation for 6 d. The me tabolism of both cholesterol and lipids was investigated in tumor cells, an d ascitic fluid and blood serum were investigated at the end of treatment, insulin prevented the reduction of food intake (19 +/- 0.6 vs. 13 +/- 0.4 g /d, P < 0.01;AH130 hosts treated and not treated with insulin, respectively ), the loss of body weight (202 +/- 12 vs. 135 +/- 9 g, P < 0.01), lowered the circulating triglycerides (48.3 +/- 4.9 vs. 84.5 +/- 7.1 mmol/L, P < 0. 01), and free fatty acids (561 +/- 47 vs. 989 +/- 54 mmol/L (P < 0.01), whi le corrected the decrease of adipose lipoprotein lipase activity (1,240 +/- vs. 300 +/- pmol FA, P < 0.01) observed in AH130 hosts, Moreover, insulin prevented the decrease in HDL cholesterol (13.2 +/- 0.8 vs. 9.3. +/- 0.7 mm ol/L, P(0.01) and significantly increased hepatic cholesterol synthesis as evaluated by C-14-acetate incorporation into cholesterol, in both liver (3, 337 +/- 245 vs. 830 +/- 115 Bq/g, P < 0.01) and AH130 cells (11,676 +/- 1,6 93 vs. 4,196 +/- 527 Bq/10(6) cells, P < 0.01). Thus insulin treatment amel iorated many metabolic derangements, with a lengthening of rats survival ti me (7 +/- 1 vs. 11 +/- 1 d, P < 0.05) without significantly stimulating tum or growth. These data, together with our previous observations on the effec tiveness of insulin on protein turnover perturbations, suggest that many me tabolic alterations occurring during cancer cachexia can be avoided by the administration of this hormone.