EFFECT OF ACUTE ACIPIMOX ADMINISTRATION ON THE RATES OF LIPID AND GLYCOGEN-SYNTHESIS IN CACHECTIC TUMOR-BEARING RATS

Increased energy expenditure in cancer cachexia may be associated with increased postprandial glycogen synthesis via an indirect pathway inv olving gluconeogenesis. The possible beneficial effects of acipimox, a nicotinic acid analogue that suppresses lipolysis and may also inhibi t gluconeogenesis, were therefore examined. Rats bearing a transplanta ble Leydig cell tumor and freely fed controls were fasted overnight, t hen given a test meal with or without 10 mg of acipimox. The meal incl uded 200 mg of [1-C-13]gluclose, and the rats were injected simultaneo usly with 7 mCi of (H2O)-H-3 and 1 mu Ci of [C-14] glycerol. The rats were killed on our later. The rate of incorporation of (H2O)-H-3 into hepatic glycogen was increased in the tumor-bearing rats and suppresse d by acipimox. Positional analysis of the tritium incorporated into gl ycogen indicated that a greater proportion of the glycogen was synthes ized via pyruvate in the tumor-bearing rats. Acipimox tended to reduce this proportion, although the effect was not statistically significan t. Neither tumor growth nor acipimox significantly affected the propor tion of C-13 incorporated into different positions in the glycogen glu cose. Glycogen synthesis from glycerol tended to decrease when lipolys is was suppressed by acipimox, although the statistical significance o f this effect was marginal. Fatty acid synthesis in liver and adipose tissue was reduced in tumor-bearing rats, but acipimox had no effect. It is concluded that acipimox does suppress gluconeogenesis and glycog enesis in the postprandial state, but it does not normalize all the me tabolic abnormalities observed in cancer cachexia.