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Soy intake reduces cholesterol levels, but neither the exact component in soy causing this reduction nor the mechanism by which cholesterol is reduced is known with certainty. In this study, a genetic screen was performed to identify hepatic mRNA in gerbils regulated by soy or soy isoflavones. Gerbils were fed casein, an alcohol-washed soy-based diet (containing low levels of isoflavones), and the soy-based diet supplemented with an isoflavone-containing soy extract. After feeding for 28 d, gerbils were killed, hepatic RNA was isolated, and genes that were differentially expressed in any of the three dietary conditions were identified. Fifteen different mRNA were originally selected, including two mRNA that were studied further and shown to be highly regulated. Messenger RNA levels for both cytochrome P450-2A and phosphoribosylpyrophosphate synthetase-associated protein were up-regulated in a dose-dependent manner when soy replaced casein in the diet at 0, 33, 67 and 100% of original casein levels. A subsequent experiment used purified amino acid mixtures resembling the percentage amino acid composition of soy and casein to ensure that isoflavone-free protein sources could be tested. Using these mixtures, a 2 x 2 x 2 design tested: natural vs. synthetic protein sources, casein- vs. soy-based diets, and isoflavone extract-supplemented or supplement-free diets. This design demonstrated that these two mRNA were again significantly up-regulated more than twofold (P < 0.05) in gerbils fed all diets containing isoflavones. Induction of these two mRNA by soy may be due to the aryl hydrocarbon receptor element in the promoter region of both genes.

To determine if alterations in growth hormone releasing factor (GRF) and somatostatin (SRIF) occur during recovery from zinc deficiency and to examine the relationship between these peptides and the increased protein intake observed during zinc repletion, both the hypothalamic release and mRNA levels of GRF and SRIF were measured during zinc deficiency and zinc repletion. Groups of male rats (n = 4-8 each) were provided 3-choice macronutrient diets made either zinc adequate (Zn+) or deficient (Zn-; 30 vs. 1 mg Zn/kg diet). Pair fed, calorie restricted (PF) rats were also maintained. After 28 days, Zn- rats were repleted with Zn+ diets for 2 days and one PF group was allowed free access to the same Zn+ diets for 2 days. Additionally, groups of Zn- and PF rats were repleted 2 days with Zn+ carbohydrate and fat diets but no protein. Hypothalamic GRF and SRIF release was measured in vitro. Basal GRF secretion was not significantly different between Zn-, PF, or Zn+ groups although there was a significant increase (P<0.05) during zinc repletion. PF and Zn- rats repleted 2 days with diets devoid of protein had highest GRF secretion (P<0.01) compared to other groups. There were no differences in GRF mRNA levels among groups. Basal SRIF secretion was significantly lower in Zn- and PF groups compared to Zn+, and SRIF mRNA levels were significantly higher in zinc repleted groups compared to Zn-. These results demonstrate that during zinc repletion, GRF and SRIF secretion and SRIF gene expression are altered concomitantly with protein intake. The present data support involvement of GRF in protein intake changes during zinc repletion.

The effects of soy protein (40 g/d) containing moderate and higher concentrations of isoflavones on blood lipid profiles, mononuclear cell LDL receptor messenger RNA, and bone mineral density and content were investigated in 66 free-living, hypercholesterolemic, postmenopausal women during a 6-mo, parallel-group, double-blind trial with 3 interventions. After a control period of 14 d, during which subjects followed a National Cholesterol Education Program Step I low-fat, low-cholesterol diet, all subjects were randomly assigned to 1 of 3 dietary groups: Step I diet with 40 g protein/d obtained from casein and nonfat dry milk (CNFDM), Step I diet with 40 g protein/d from isolated soy protein containing 1.39 mg isoflavones/g protein (ISP56), or Step I diet with 40 g protein/d from isolated soy protein containing 2.25 mg isoflavones/g protein (ISP90). Total and regional bone mineral content and density were assessed. Non-HDL cholesterol for both ISP56 and ISP90 groups was reduced compared with the CNFDM group (P < 0.05). HDL cholesterol increased in both ISP56 and ISP90 groups (P < 0.05). Mononuclear cell LDL receptor mRNA was increased in subjects consuming ISP56 or ISP90 compared with those consuming CNFDM (P < 0.05). Significant increases occurred in both bone mineral content and density in the lumbar spine but not elsewhere for the ISP90 group compared with the control group (P < 0.05). Intake of soy protein at both isoflavone concentrations for 6 mo may decrease the risk factors associated with cardiovascular disease in postmenopausal women. However, only the higher isoflavone-containing product protected against spinal bone loss.

This study examined how macronutrient intake preferences were specifically altered in the loss of appetite caused by experimentally produced zinc deficiency. Outbred female rats were allowed to freely select from simultaneously provided carbohydrate-, protein-, and fat-rich diets to provide themselves with an acceptable total diet. Rats were divided into two groups and provided the three diets containing either adequate (30 mg/kg; Zn+) or deficient (1 mg/kg; Zn-) levels of zinc (Zn). After 28 d, rats offered the Zn- diet were returned to a Zn+ diet (Zn repletion). Intakes from each of the three macronutrient diets were measured to determine macronutrient preferences of Zn-adequate, Zn-deficient, and Zn-repleted rats. In two 28-d studies involving a total of 66 rats, total metabolizable energy intake in Zn deficient rats was between 20 and 35% lower than in Zn+ rats, and carbohydrate intake accounted for essentially 100% of the lower energy intake. Fat and protein intakes were not affected by Zn deficiency. When Zn-deficient rats were repleted with Zn by providing diets containing adequate Zn, carbohydrate intake was restored to normal levels after 1 d of feeding. A transient difference in protein intake was noted during the repletion period, peaking during d 2-4 of repletion. Protein intake increased by more than 50% during this period. We hypothesize that specific changes in macronutrient intake patterns during development and recovery from Zn deficiency may be reflections, at least in part, of Zn-mediated changes in the central control of appetite.