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 involving gluconeogenesis. The possible beneficial effect of acipimox, a nicotinic acid analogue that suppresses lipolysis and may also inhibit gluconeogenesis, were therefore examined. Rats bearing a transplantable Leydig cell tumor and freely fed controls were fasted overnight, then given a test meal with or without 10 mg of acipimox. The meal included 200 mg of [1-13C]glucose, and the rats were injected simultaneously with 7 mCi of 3H2O and 1 microCi of [14C]glycerol. The rats were killed one hour later. The rate of incorporation of 3H2O into hepatic glycogen was increased in the tumor-bearing rats and suppressed by acipimox. Positional analysis of the tritium incorporated into glycogen indicated that a greater proportion of the glycogen was synthesized via pyruvate in the tumor-bearing rats. Acipimox tended to reduce this proportion, although the effect was not statistically significant. Neither tumor growth nor acipimox significantly affected the proportion of 13C incorporated into different positions in the glycogen glucose. Glycogen synthesis from glycerol tended to decrease when lipolysis was suppressed by acipimox, although the statistical significance of 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 glycogenesis in the postprandial state, but it does not normalize all the metabolic abnormalities observed in cancer cachexia.
Obeid
O A
OA
Department of Nutrition and Dietetics, King's College London, UK.
Emery
P W
PW
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002100:Cachexia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000097:blood / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis*; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007984:Leydig Cell Tumor / Q000150:complications; D008055:Lipids / Q000096:biosynthesis*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D011719:Pyrazines / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013736:Testicular Neoplasms / Q000150:complications*
D001786:Blood Glucose; D000960:Hypolipidemic Agents; D008055:Lipids; D011719:Pyrazines; D006003:Glycogen; D005947:Glucose; C027696:acipimox; D005990:Glycerol