Reduced food intake in zinc deficient rats is normalized by megestrol acetate but not by insulin-like growth factor-I.
Zinc deficiency in rats results in impaired growth accompanied by decreased and cyclic food intake. These signs are associated with decreased plasma insulin-like growth factor-I (IGF-I), a major mediator of growth. The purpose of this study was to determine the relationship between decreased plasma IGF-I and the impairment of appetite and growth in zinc deficiency. Immature male rats were fed free choice a low zinc (<1 mg/kg) diet (-Zn) or a zinc adequate (100 mg/kg) control diet (+Zn). Plasma IGF-I concentrations were normalized in zinc-deficient rats by the following two methods: osmotic pump infusion of IGF-I (2.4 mg/kg body weight daily) and oral administration (50 mg/kg body weight twice daily) of the synthetic progestin, megestrol acetate (MA). Infusion of IGF-I for 8 d sustained plasma IGF-I concentrations in zinc-deficient rats at control levels but had no effect on either food intake or growth rate. MA administration for 8 d maintained the plasma IGF-I of deficient rats and significantly increased food intake. The early aspects of cyclic food intake were eliminated, and, after a few days, food intake of deficient rats given MA was not different than that of controls. MA increased food intake and fat deposition regardless of zinc status, but it had no effect on the growth rate of deficient rats. MA significantly decreased body weight of controls, uncoupling energy intake and gain. The results suggest that reduced food intake precedes the decreased plasma IGF-I concentration and that IGF-I is not responsible for the decreased growth and food intake of zinc-deficient rats. The appetite and growth impairment of zinc-deficient rats may arise from disrupted function of IGF-I receptors in the brain and peripheral tissues, but not from low circulating levels of IGF-I.
Browning
J D
JD
Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
MacDonald
R S
RS
Thornton
W H
WH
O'Dell
B L
BL
D000273:Adipose Tissue; D000818:Animals; D019167:Appetite Stimulants / Q000494:pharmacology*; D001823:Body Composition; D004032:Diet; D004435:Eating / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D019290:Megestrol Acetate / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015430:Weight Gain / Q000187:drug effects; D015032:Zinc / Q000008:administration & dosage / Q000172:deficiency*
D019167:Appetite Stimulants; D007334:Insulin-Like Growth Factor I; D015032:Zinc; D019290:Megestrol Acetate