Dietary protein and lipid metabolism: a multifunctional effect.
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Biomedical subjects
Publications and source records attributed to M Sugano.
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The effect of dietary protein, casein (CAS) and soybean protein (SOY), on linoleic acid desaturation in liver microsomes was studied in rats. The activity of delta 6 desaturase in total and rough endoplasmic reticula (ER and RER) was significantly higher in the CAS group than in the SOY group. In ER and smooth endoplasmic reticulum, the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene, when incorporated into the membrane, was decreased in the SOY group and accompanied by a reduction in the cholesterol/phospholipid (CHOL/PL) ratio, consistent with an increase in membrane fluidity. In a separate study, the effect of varying dietary proteins, CAS, milk whey protein, egg albumin, SOY, potato protein and wheat gluten, on the relationship between the delta 6 desaturase activity and microsomal membrane fluidity was also examined. The results indicated that the dietary protein-dependent change in the liver microsomal CHOL/PL ratio affected membrane fluidity, and subsequently the activity of delta 6 desaturase in liver microsomes. However, since dietary protein influenced the delta 6 desaturase activity in RER without influencing membrane fluidity, it is possible that some regulation might have taken place at the level of enzyme synthesis.
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Lymphatic transport of docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids given in the forms of triglyceride, ethyl ester of free acid and their effect on cholesterol transport was compared in lymph-cannulated rats. Lymphatic recovery of DHA and EPA given by stomach tube in the form of triglyceride in which they were mainly located at the 2-position was significantly higher than that of the ethyl ester or free acid during the first 6 hr after the administration and the tendency continued until 9 hr. In contrast, the 9 to 24 hr recovery of DHA and EPA in the forms of ethyl ester and free acid was considerably higher than that of triglyceride. Consequently, cumulative 24 hr recovery of EPA was comparable among the three forms. However, the 24 hr recovery of DHA was highest in free acid, lowest in ethyl ester and intermediate in triglyceride. Recovery of the free acid between 9 and 24 hr after administration was significantly higher than that given in the forms of triglyceride or ethyl ester. Cholesterol recovery in lymph of rats given with ethyl ester or free acid was lower than that given with triglyceride at an early stage after the administration in both EPA and DHA. Cumulative 24 hr recovery of cholesterol in rats given these fatty acids as ethyl ester was significantly lower than in those given as the other two forms.
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Curcuma xanthorrhiza Roxb., a medicinal plant used in Indonesia, has been shown to exert diverse physiological functions. However, little attention has been paid to its effect on lipid metabolism. We have investigated the effects of C. xanthorrhiza on serum and liver lipids, serum high density lipoprotein (HDL)-cholesterol and apolipoprotein (apo) A-I, and liver lipogenic enzymes in rats. In rats given a cholesterol-free diet, C. xanthorrhiza decreased the concentrations of serum triglycerides and phospholipids, and liver cholesterol, and increased serum HDL-cholesterol and apo A-I. The activity of liver fatty acid synthase, but not glycerophosphate dehydrogenase, was decreased by the medicinal plant. In rats on a high-cholesterol diet, C. xanthorrhiza did not suppress the elevation of serum cholesterol, although it did decrease liver cholesterol. Curcuminoids prepared from C. xanthorrhiza had no significant effects on the serum and liver lipids. These studies, therefore, indicate that C. xanthorrhiza contains an active principle(s) other than curcuminoids which can modify the metabolism of lipids and lipoproteins.
To examine the effect of different saturated fatty acids on the dietary cholesterol-induced elevation of serum cholesterol concentration and suppression of LDL catabolism, for 4 wk hamsters were fed purified diets containing 8% purified fats in which saturated fatty acids, lauric, myristic, palmitic and stearic acids were the sole variable. The dietary fat was composed of 50% saturated fatty acid, 30% oleic acid and 20% linoleic acid (polyunsaturated:saturated = 0.4). In hamsters fed the cholesterol-containing diet, fat containing stearic acid, compared with the fats containing other saturated fatty acids resulted in greater fractional catabolic rate of [125I]-labeled homologous LDL, greater fecal excretion of neutral steroids and lower liver cholesterol concentration, although the elevation of serum cholesterol concentration due to consuming a cholesterol-containing diet was not ameliorated. Stearic acid fat resulted in greater excretion of fecal fatty acids and lower apparent absorption of the dietary fats in hamsters fed diets with and without cholesterol. In hamsters fed the cholesterol-free diets, type of dietary fat did not affect the fractional catabolic rate of LDL, although stearic acid fat resulted in greater fecal neutral steroid excretion and lower serum and liver cholesterol concentrations. These observations suggested that purified fat containing stearic acid results in lower plasma cholesterol concentration in hamsters via stimulation of neutral steroid excretion, but addition of cholesterol to the diets obscures this effect.
The effect of dietary protein, either casein (CAS) or soybean protein (SOY), on the polyunsaturated fatty acid (PUFA) composition of liver microsomal phospholipids and eicosanoid production was compared in normal and streptozotocin-induced diabetic rats fed diets containing perilla oil rich in alpha-linolenic acid. In normal rats the linoleic acid desaturation index in liver microsomal phospholipids was significantly higher in the CAS group than in the SOY group, whereas it was reversed in diabetic rats. The proportion of eicosapentaenoic acid (EPA) decreased in diabetic rats, in particular those fed SOY, whereas it was vice versa for arachidonic acid (AA). The ratio of aortic prostacyclin production to platelet thromboxane A2 production decreased only in diabetic rats fed SOY reflecting a reduction of the EPA/AA ratio. Thus, dietary protein differently modified the PUFA composition and eicosanoid balance even in the diabetic rat. In this respect, alpha-linolenic acid seemed to be less influential than linoleic acid.
The effects of sesamin, a potent inhibitor of delta 5-desaturase in polyunsaturated fatty acid biosynthesis, on the fatty acid compositions of tissue lipids and liver functions were examined in rodents. When a mixture of sesamin and episesamin (51.1:48.2, w/w) was given to rats at a dietary level of 0.5% for 13 days, the proportions of dihomo-gamma-linolenic acid significantly increased not only in the liver but also in plasma and hemocytes, suggesting an interference with delta 5-desaturation by these lignans. The sesamin preparation at the dietary level of 1% improved changes in various blood parameters of the mouse, such as aspartate aminotransferase and alanine aminotransferase activities, and the concentrations of total cholesterol, triglyceride and total bilirubin, caused by continuous inhalation of ethanol. In addition, sesamin showed a significant protective effect against the accumulation of fat droplets and vacuolar degeneration in the mouse liver, as confirmed on histological examination. Sesamin, at the level of 100 mg/kg body weight, also tended to prevent liver lipid accumulation by carbon tetrachloride in mice. These results indicate that sesamin and a related lignan compound have an ability to improve liver function.
Inhibitors of the protease of human immunodeficiency virus type-1 (HIV-1) were designed and synthesized. A reduced peptide, simple aminoalcohol, and statine analog, 4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA), were inserted at the scissile site of substrate sequences of HIV-1 protease. While both reduced peptides and simple aminoalcohol derivatives were weak inhibitors, the peptides containing AHPPA demonstrated moderate inhibitory activity. The more potent alcohol configuration of AHPPA is (R), which is opposite to the configuration in potent inhibitors of other aspartic proteases. In particular, compound 28 ((3R,4S)-4-(N-tert-butoxycarbonyl- L-glutaminyl-L-asparaginyl)amino-3-hydroxy-5-phenylpentanoic acid 2'-methylbutylamide) had a Ki of 0.36 microM and exhibited excellent enzyme specificity.
Human immunodeficiency virus type 1 (HIV-1) protease inhibitors containing four types of hydroxyethylene dipeptide isosteres were designed and synthesized. These inhibitors consist of eight stereoisomers of phenylalanylproline (Phe-psi[H.E.]-Pro), four stereoisomers of phenylalanylalanine [Phe-psi[H.E.]-Ala), and one stereoisomer each of phenylalanylglycine (Phe-psi[H.E.]-Gly) and cyclohexylalanylalanine (Cha-psi[H.E.]-Ala) hydroxyethylene dipeptide isosteres. For the synthesis of the latter two isosteres, a newly developed synthetic method for gamma-lactone was applied. The inhibitory activities of these peptides were evaluated by cleavage assay of partially purified gag proteins or purified synthetic peptide. Of the inhibitors examined, compounds 2c (Z-Asn-(2S,3R,4S,5S)-Phe-psi[H.E.]-Pro-NHB(un); Bu(n) = n-butyl, Ki = 0.50 microM), 21a (Z-Asn-(2R,4S,5S)-Phe-psi[H.E.]-Ala- NHBu(n), Ki = 0.34 microM) and 23 (Z-Asn-(2R,4S,5S)-Cha-psi[H.E.]-Ala- NHBu(n), Ki = 0.46 microM) were moderately potent inhibitors. The results revealed that the alkyl substituent at C2 is essential, and the stereochemistry of the hydroxyethylene dipeptide isosteres greatly affected their inhibitory activities.
Rhizomes of Curcuma xanthorrhiza Roxb. (C. xanthorrhiza), a medicinal plant in Indonesia, has been shown to exert diverse physiological functions. Hitherto, a little attention has been paid to its effect on immune functions. This study was carried out to determine the effect of this medicinal plant on mitogenic response of splenic lymphocytes in rats and population of splenic lymphocytes and macrophages and peripheral blood macrophages in mice. Mitogenic responses of splenocytes to phytohemagglutinin, concanavalin A, and pokeweed mitogens were examined in rat fed C. xanthorrhiza for 3 weeks. The medicinal plant increased the blastogenesis to these mitogens. Flow cytometric analysis was carried out for mice fed the medicinal plant for 3 to 5 weeks. C. xanthorrhiza increased the proportion of the splenic T cells throughout the experimental period, but exerted a variable effect on B cells and T cell subsets, that is, elevations of B cells at 3 weeks and of Th cells at 4 weeks without any elevation of Ts cells. The effect of this medicinal plant on a proportion of macrophages from the spleen and peripheral blood was not consistent. Thus, the present study suggests that C. xanthorrhiza contains some principle(s) activating T and B cell-mediated immune functions.
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Although cyclophosphamide pulse therapy has been reported to be beneficial for patients with chronic progressive multiple sclerosis for whom other treatment modalities are not expected to improve outcome, the experience with Japanese patients has not been shown in the literature. The reason appears due, in part, to the small size of this group and to the side effects inherent to such a large dose immunosuppressive regimen. Here, we report on 3 cases with chronic progressive multiple sclerosis who have undergone the pulse-dose cyclophosphamide treatment. The cases included 3 women, two with primary progressive multiple sclerosis (one, the classical form and the other, the spinal cord from). The 3rd case was that of myelitis-optic neuritic form and the total blindness of right eye (left side had been totally blind) was impending despite repeated corticosteroid therapies. The regimen included 600 mg/m2 intravenous cyclophosphamide per day at days 1, 2, 4, 6, 8 and infusion of totally 2,500-3,000 ml of intravenous fluid in order for avoiding hemorrhagic cystitis. The side effects were nausea, anorexia, leucopenia (10-15 days from the end of the course and the lowest value being 1,100/microliters), microscopic hematuria in one case, and alopecia in all. All the patients tolerated the therapy well. Two cases improved to a significant degree and the 3rd case with impending blindness has shown the arrest of progression. However, two of them began progressing again in one- to two-year period and the pulse-dose had to be repeated. These 3 cases have shown neurological improvements or at least arrest of the progression following the therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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The amount of intestinal apolipoprotein (apo) A-IV mRNA was examined in rat pups during fasting and refeeding. When 14-day old pups were fasted for 15 h, apo A-IV mRNA levels in the whole intestine decreased to 20% of the prefasting level. Refeeding casein and lactose, and the artificial milk composed of Intralipid, casein and lactose, caused an elevation of the apo A-IV mRNA after 3 h, without accompanying an elevation of serum triacylglycerols and apo A-IV (fat-independent elevation of apo A-IV mRNA). Refeeding Intralipid alone simultaneously elevated the apo A-IV mRNA, and serum triacylglycerols and apo A-IV after 3 h (fat-dependent elevation of apo A-IV mRNA). Administration of physiological saline during fasting partly suppressed the reduction of the apo A-IV mRNA (40% of the prefasting level), and the dietary fat-independent elevation of the message disappeared. Refeeding dam's milk to the pups, fasted without water administration, increased the apo A-IV mRNA after 3 and 15 h, although the elevation of serum triacylglycerols and apo A-IV occurred only after 15 h. Refeeding the milk increased the apo A-IV mRNA after 3 h and 15 h. Refeeding dam's milk to the pups fasted with saline administration accelerated the fat-dependent elevation of the apo A-IV mRNA. Simultaneously refeeding Intralipid and Pluronic L-81, an inhibitor of lymphatic fat transport, delayed the elevation of the apo A-IV mRNA and serum triacylglycerols and apo A-IV. Transcription rates of the apo A-IV mRNA, determined by nuclear run/on assay, were similar before and after fasting and refeeding Intralipid. During fasting, administration of puromycin, as compared with actinomycin D, enhanced the disappearance rate of the apo A-IV message. Intestinal mRNA for apo B, but not for apo A-I and beta-actin, similarly changed to the apo A-IV message. Thus, it can be concluded that: (1) dietary fat-dependent and -independent factors are involved in the elevation of the intestinal apo A-IV message; (2) the elevation of the message is not mediated by lipid uptake in the enterocytes but rather stimulated by the events leading to secretion of chylomicrons; and, (3) dietary fat-dependent elevation of the message appears to be due to the stabilization of the message.
A(-)-epicatechin (EC) and (-)-epigallocatechin (EGC) mixture and a mixture of their gallates (ECG and EGCG, respectively) markedly lowered lymphatic cholesterol absorption in rats with a cannulated thoracic duct. A mixture of ECG and EGCG was more effective in reducing cholesterol absorption than the EC and EGC mixture. These catechins also tended to decrease lymphatic absorption of triacylglycerols, although not so pronounced as in cholesterol absorption. An in vitro study on micellar solubility of cholesterol showed that these catechin mixtures precipitated cholesterol solubilized in mixed bile salt micelles in a dose-dependent manner. A mixture of ECG and EGCG more effectively precipitated micellar cholesterol than a mixture of EC and EGC. When purified EC, EGC, ECG and EGCG were used, EGCG was more effective in precipitating micellar cholesterol than ECG. The effect of EC and EGC was comparable and weaker than their gallate esters. The bile acid concentration in the micelles was not affected by these catechins. A positive correlation was observed between the amount of coprecipitated EGCG and cholesterol. These results clearly show that tea catechins, in particular their gallate esters, effectively reduce cholesterol absorption from the intestine by reducing solubility of cholesterol in mixed micelles. The observation accounts for the hypocholesterolemic effect of tea catechins.