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We investigated the role of zinc in food intake regulation using rats during early-stage zinc deficiency without decreased zinc concentrations in plasma and tissues. Plasma, liver, and hypothalamic zinc concentrations were not affected in male Sprague-Dawley rats fed a zinc-deficient (Zn-Def) diet for 3 d compared with the pair-fed control group, which was fed a zinc-sufficient diet to the intake of the Zn-Def diet. Zinc sulfate at a dose of 19 [micro]mol/kg body weight was orally or intraperitoneally (i.p.) administered to rats fed a Zn-Def diet for 3d and food intake was measured. We found that zinc stimulated food intake after oral but not i.p. administration. The mRNA expression of neuropeptide Y (NPY) and orexin in the hypothalamus significantly increased 3 h after oral but not i.p. administration of zinc. Pretreatment with an antagonist for the NPY [Y.sub.1] receptor or the orexin [OX.sub.1] receptor blocked orexigenic activity after oral administration of zinc. The stimulation of food intake by oral administration of zinc was abolished by vagotomy. Taken together, orally administered zinc may stimulate food intake via orexigenic peptides coupled to the afferent vagal stimulation in rats after short- term treatment with a Zn-Def diet.

Tocotrienol (T3), unsaturated vitamin E, has recently gained considerable attention as a potent antiangiogenic agent minimizing tumor growth, the exact intracellular mechanisms of which remain poorly understood. Because hypoxiainducible factor-1[alpha] (HIF-1[alpha]), its downstream target vascular endothelial growth factor (VEGF), and other angiogenic factors such as interleukin-8 (IL-8) and cyclooxygenase 2 (COX-2) play critical roles in neovascularization, we tested the hypothesis that the inhibitory effect of T3 on tumor angiogenesis is via regulation of these angiogenic factors. We used 2 cancer cell lines, human colorectal adenocarcinoma cells (DLD-1) and human hepatoma cells (HepG2). T3 isomers (2 [micro]mol/L) inhibited hypoxia-induced VEGF secretion from DLD-1, with [delta]-T3 showing potent inhibition. [delta]-T3 suppressed hypoxia-induced VEGF and IL-8 expression in DLD-1 at both mRNA and protein levels, and we found the inhibitory mechanism of [delta]-T3 by reducing HIF-1[alpha] protein expression or increasing HIF-1[alpha] degradation. Also, [delta]-T3 (2 [micro]mol/L) did not affect hypoxia-induced COX-2 mRNA expression; however, [delta]-T3 tended to suppress (P = 0.044) hypoxia-induced COX-2 protein expression, implying a possible post-transcriptional mechanism by [delta]-T3. Overall, our results confirmed that T3 has an inhibitory effect on angiogenic factor secretion from cancer cells and revealed the possible mechanisms, providing new information about the antiangiogenic effects of T3.

We previously showed that [alpha]-eleostearic acid ([alpha]-ESA; 9Z11E13E-18:3) is converted to conjugated linoleic acid (CLA; 9,11-18:2) in the liver and plasma of rats that were given diets including 1% [alpha]-ESA for 4 wk. In this study, we investigated this phenomenon in detail. First, the chemical structure of CLA produced by [alpha]-ESA administration was determined. After [alpha]-ESA was orally administered to rats, CLA in rat liver was isolated by HPLC. The positional and geometric isomerism was determined using GC-EI/MS and [sup.13.C]-NMR, respectively, and the CLA. generated in rats after [alpha]-ESA feeding was confirmed to be 9Z11E-CLA. Next, the concentrations of [alpha]-ESA and CLA were determined 0, 3, 6, and 24 h after oral administration of [alpha]-ESA to rats. Moreover, we also investigated whether enteric bacteria are involved in the conversion of [alpha]-ESA to CLA using germ-free rats. [alpha]-ESA was orally administered to germ-free and normal rats and [alpha]-ESA and CLA were detected in the organs of both groups. In addition, to confirm that this reaction was enzyme-mediated, [alpha]-ESA was reacted with tissue homogenates (liver, kidney, and small intestine mucous) and coenzymes (NADH, [NAD.sup.+], NADPH, and [NADP.sup.+]), and the enzyme activities were estimated from the amount of CLA produced. CLA was detected when [alpha]-ESA was reacted with liver, kidney, and small intestine mucous homogenates and a coenzyme (NADPH). These results indicated that [alpha]-ESA is converted to 9Z11E-CLA in rats by a [DELTA]13-saturation reaction carried out by an NADPH-dependent enzyme. KEY WORDS: * conjugated linoleic acid * conjugated linolenic acid * eleostearic acid * germ-free rat * GC-EI/MS

Antibiotic novobiocin is capable of generating cation channels in lipid bilayers and increases salt taste response in rats through regulation of amiloxide-sensitive sodium channels. Single fibers of the rat chorda tympani nerve aid the examination of the role of novobiocin in salt taste transduction. Novobiocin increases the responses of N-type fiber to 100 mM NaCl but does not influence the response of E-type fibers to either 100 mM KCl or 100 mM NaCl.

The effects of zinc deficiency on taste sensitivity were examined in rats by recording the electrophysiological responses of the chorda tympani (CT) nerve and by use of a preference test. Male 4-wk-old Sprague-Dawley rats were given free access to a diet containing 2.2 (zinc-deficient), 4.1 (low zinc) or 33.7 (zinc-sufficient) mg zinc/kg diet. A fourth group was pair-fed the zinc-sufficient diet (with respect to the zinc-deficient rats). A two-bottle preference test using 0.15 mol/L NaCl and water revealed that NaCl preference was greater in the zinc-deficient and low zinc groups than in the control groups (zinc-sufficient and pair-fed) after 4 d of feeding. In the case of quinine hydrochloride solution (0.01 mmol/L), the preference was greater in zinc-deficient rats than in the other groups after 9 d, and the low zinc rats never showed a preference. Electrophysiological recording indicated that in the zinc-deficient rats, the CT nerve response to 0.20 mol/L NaCl was significantly less than that in the control rats after 21 d of feeding. In the low zinc rats, this response was significantly less than in the control rats after 35 d. The responses to quinine hydrochloride (0.02 mol/L), L-glutamic acid, HCl (0.01 mol/L) and [NH.sub.4]Cl (0.25 mol/L) in the zinc-deficient rats were not significantly reduced until d 42. These findings suggest that long-term zinc deficiency decreases taste sensitivity at the level of the CT nerve and that the change in NaCl preference due to zinc deficiency occurs before any change in NaCl taste sensitivity. J. Nutr. 131: 305-310, 2001. KEY WORDS: * zinc deficiency * chorda tympani nerve * taste abnormality * NaCl preference * rats