Now it is known that beta-carotene (β-carotene) has other important biological functions in addition to the role of vitamin A precursor. The various epidemiological studies suggested that high β-carotene intake might reduce the incidence of the cancer risk. Although several studies are under way to find biological evidence for the epidemio-logical results, the mechanism of action of β-carotene is still unknown. As the first step to elucidate the biological functions of β-carotene, we investigated the mobilization and the distribution of all-trans-a-carotene in the rat. Because it was reported that the rat did not absorb the intact form of β-carotene, we injected a β-carotene suspension intravenously (dose; 2.0mg/rat). After injection, a high amount of β-carotene (about 1.5mg-2.0mg) accumulated in the lung very rapidly (within 5 min). By this method, the time-dependent mobilization and distribution of β-carotene in the rat was as follows: all-trans-β-carotene was accumulated in the lung then moved to the liver, was distributed in adipose tissues (after 1 week), pancreas (after 2 weeks), and muscle tissue or testis (after 3 weeks).
Sodium alginate, mannuronic acid-rich and guluronic acid-rich fractions were prepared from “Mekabu” (sporophyll of Undaria pinnatifida). The production of short-chain fatty acids such as acetic, propionic and n-butyric acids from these fractions in mini-scale batch culture using pig cecal bacteria was studied, and the gas released from the culture was monitored. The volume of released gas corrected for blank value decreased in the order: glucose (a reference substrate)>guluronic acid-rich fraction >sodium alginate=mannuronic acid-rich fraction. The amounts of short-chain fatty acids produced from three fractions of alginic acid were smaller than that of glucose. These results suggested that alginic acid was poorly fermentable for hindgut bacteria and that its contribution to the host energy pool via microbial metabolism is small.
The significant antihypercholesterolemic effect of the un-digested high molecular fraction (HMF) of soybean protein is known in rats, but such an effect has not been shown in humans. The present two experiments were designed to elucidate it in humans. Subjects were female university students who had relatively high serum cholesterol levels for their age. In Experiment 1, subjects took 8% of their total energy from casein, soybean protein isolate (SPI), or HMF daily for 14 days. Five basic menus and snacks were cycled. Energy intakes and daily activities were kept constant and body weight was maintained. The HMF group showed decreased low-density lipoprotein cholesterol (LDL-C) as compared to other groups. In Experiment 2, subjects took 4% of total energy from casein or HMF daily for a menstruation period. Five basic menus and snacks which contained two egg yolks (about 500 mg choles-terol) were cycled. Energy intakes and daily activities were kept constant and body weight was maintained. A decrease in LDL-C and an increase in high-density lipoprotein cholesterol (HDL-C) were observed in the HMF group as compared to the casein group. Fecal acidic steroid excretion was greater in the HMF group than in the casein group (p<0.05). The results confirmed that HMF increases fecal steroid excretion and reduces serum cholesterol levels in humans.
Hepatic cystathionine β-synthase activity is decreased by the addition of cysteine to the diet. This effect of cysteine was slightly greater in diets containing 0.25% methionine than in those containing 1 % methionine, and was reduced during aging. Similar changes were ob-served in the level of the mRNA of this enzyme, although the changes in the trancscript levels were slightly greater than the changes in enzyme activity. Thus, we conclude that the addition of cysteine to a methionine-containing diet causes a decrease in cystathionine Q-synthase activity mainly by diminishing its mRNA level.
The effects of dietary polyunsaturated fat on insulin-dependent gene expression of lipogenic enzymes and a possible mechanism for PUFA-mediated suppression of the gene expression have been in-vestigated in rat livers. When diabetic rats were injected with insulin, the insulin dose-dependent induction of lipogenic enzyme mRNAs were markedly reduced with increasing dietary corn oil. On the other hand, the PUFA-mediated suppression of the mRNA concentrations was partially restored by treatment with pioglitazone, a candidate for increasing insulin receptor phosphorylation. Moreover, insulin binding to receptors of liver, receptor autophosphorylation, and kinase activity toward exogenous sub-strate were lower in the corn oil diet group than in the hydrogenated fat group. The PUFA-mediated suppression of insulin binding was some-what restored by pioglitazone, and the suppression of insulin receptor phosphorylation was significantly restored. It is suggested that the PUFA-mediated suppression of insulin-dependent gene expression of lip-ogenic enzymes can be ascribed to a decrease in insulin receptor binding primarily and also to receptor phosphorylation. Thus, PUFA appears to suppress the lipogenic enzyme gene expression stimulated by insulin.
Sesamin is known as a specific inhibitor of Δ-desaturation, the conversion from dihoo-γ-linolenic acid (20: 3(n-6)) to arachidonic acid (20:4(n-6)). In the previous paper, we reported that sesamin inhibited Δ-desaturation of n-6 fatty acids in rat hepatocytes but not that of n-3 fatty acids, from 20: 4(n-3) to 20: 5(n-3). Then, we studied the effects of sesamin on Δ-desaturation of n-6 and n-3 fatty acids in vivo. Rats were fed two types of diets containing sesamin (0.5% w/w) for 4 weeks as follows: in experiment 1 (Exp. 1) γ-linolenic acid-rich diet and in experiment 2 (Exp. 2) a-linolenic acid-rich diet. The fatty acid composi-tion of liver lipids was compared to those of control groups without sesamin. In both Exps. 1 and 2, sesamin increased the liver weight and phospholipid contents in liver. In Exp. 2, sesamin increased n-6 fatty acids and decreased n-3 fatty acids even though the diet was rich in n-3 fatty acids. Sesamin enhanced the composition ratio of 20: 3(n-6) in both Exps. 1 and 2. Decrease of Δ-desaturation index of n-6 fatty acid, the ratio of 20:4(n-6)/20: 3(n-6), by the administration of sesamin suggested that sesamin inhibited the Δ-desaturation of n-6 fatty acids in the liver. On the contrary, the Δ-desaturation index of n- 3 fatty acids, the ratio of 20: 5(n-3) to 18: 3(n-3), was increased by sesamin administration in the liver of rats fed a-linolenic acid-rich diet (Exp. 2). These results sug-gested that sesamin inhibited the Δ-desaturation of n-6 fatty acids but not that of n-3 fatty acids in vivo similarly to results from rat hepatocytes.
To investigate molecular mechanisms of growth control by protein nutrition, we examined whether nutritive quality of protein affects the induction of DNA synthesis in liver and kidney of growing rats in relation to expression of growth-related genes such as c-myc, c-fos, c-Ha-ras, and ornithine decarboxylase (ODC). Rats were adapted to 2-h meal feeding schedule at first with laboratory chow for 10 days and then with a protein-free diet for 3 days prior to experiments. When protein-free diet was fed to the rats, the levels of c-myc, ODC and c-Ha-ras mRNAs increased in the liver within 2 days. However, substantial changes in the levels of those mRNAs were not observed in the kidney. The level of c fos mRNA in these tissues was too low to detect by our method. Feeding of casein diet to rats that had been maintained on protein-free diet for 3 days caused a rapid decrease in the level of c-myc mRNA and induced DNA synthesis in the liver. On the other hand, zein diet, which lacks tryptophan and lysine, did not lower the c-myc mRNA level nor induced DNA synthesis in the liver. However, if zein diet was supplemented with tryptophan and lysine, a decrease in c-myc mRNA level and an induction of DNA synthesis were observed. The levels of ODC and c-Ha-ras mRNAs were not changed by feeding of casein or zein diet. Neither casein nor zein induced DNA synthesis and changed the levels of the mRNA in the kidney. The amount of food intake during the 2-h feeding period was not different among the diets. These results suggest that the liver cells are arrested in G 1 phase during the feeding of protein-free diet and good quality of protein is required to progress the cell cycle to enter S phase.
The concentration of epidermal growth factor (EGF) in human milk was measured by radioreceptor assay (RRA). Human milk samples collected from healthy Japanese mothers who delivered at full term were divided into 30 groups according to differences in the duration of lactation, seasons of the year and place of residence. Human milk collected from 3 to 5 days after delivery in winter and summer contained 15.03, μg/100 ml and 15.46 μg/100 ml of EGF, respectively. The concen-trations decreased rapidly to 8.04 μg/ 100 ml and 8.12 μg/ 100 ml in milk from 31 to 60 days, and to 5.10 μg/ 100 ml and 5.44 μg/ 100 ml in milk from 241 to 481 days. Seasonal and regional differences in EGF concentration were observed to some extent, but no clear tendency could be defined. These results suggest that EGF is an essential and fundamental factor for the growth of infants in the very early stages after delivery, because it was high only at the beginning of lactation and then it decreased.
The response of apolipoproteins, which are synthesized mainly in the small intestine, after small bowel resection has not been documented. In this study, we investigated the effect of small bowel resection on the expression of apolipoprotein mRNA in the residual ileum in rats. Wistar rats underwent either an 85% jejunoileal resection or a sham-operation. Plasma concentrations of total and HDL-cholesterol, apolipoprotein A-I and A-IV were measured on days 0, 3, 6, 9, 12, and 16 (surgery on day 1). The abundances of apolipoprotein mRNA in the residual ileum and liver on day 16 were determined. Plasma levels of total and HDL-cholesterol and apolipoprotein A-I and A-IV in resected rats were significantly lower than in sham-operated rats on days 3 and 6. Resected rats showed a significant increase in ileal apolipoprotein A-I (1.2-fold) and A-IV (3.2-fold) mRNA compared with sham-operated animals. Hepatic apolipoprotein mRNA were the same between two groups. These data suggest that the residual ileum adapts to jejunoileal resection by selective increases in apolipoprotein A-I and A-IV expression at a pretranslational stage. The recoveries of apolipoprotein A-I and A-IV in plasma appear to depend, at least in part, on the increased expression of these apolipoproteins in the residual ileum.
The intestinal absorption efficacy of 2-O-α-D-glucopyrano-syl-L-ascorbic acid (AA-2G), which has been recently synthesized and characterized as a stable ascorbate (ASA), was determined in guinea pigs by the perfusion technique. Perfusion of AA-2G in isotonic phosphate buffer to the small intestine resulted in a decrease of AA-2G accompanied by an increase of AsA in the perfusate. The results showed that intact AA-2G was not detected in the plasma of the portal vein of guinea pigs at 2 h after perfusion. The disappearance of AA-2G from perfusate was completely inhibited by the addition of castanospermine, a specific a-glucosidase inhibitor, or by carbohydrates such as maltose. These results indicate that ascorbic acid released from AA-2G by a-glucosidase on the brush border membrane is effectively taken up across the intestinal ascorbate transport channels, into a serosal site, whereas AA-2G permea-tion was poor via the passive transport system.