Interaction between dietary methionine and methyl donor intake on rat liver betaine-homocysteine methyltransferase gene expression and organization of the human gene.
(41/20742)
We previously showed that rat liver betaine-homocysteine methyltransferase (BHMT) mRNA content and activity increased 4-fold when rats were fed a methionine-deficient diet containing adequate choline, compared with rats fed the same diet with control levels of methionine (Park, E. I., Renduchintala, M. S., and Garrow, T. A. (1997) J. Nutr. Biochem. 8, 541-545). A further 2-fold increase was observed in rats fed the methionine-deficient diet with supplemental betaine. The nutrition studies reported here were designed to determine whether other methyl donors would induce rat liver BHMT gene expression when added to a methionine-deficient diet and to define the relationship between the degree of methionine restriction and level of methyl donor intake on BHMT expression. Therefore, rats were fed amino acid-defined diets varying in methionine and methyl donor composition. The effect of diet on BHMT expression was evaluated using Northern, Western, and enzyme activity analyses. Similar to when betaine was added to a methionine-deficient diet, choline or sulfonium analogs of betaine induced BHMT expression. The diet-induced induction of hepatic BHMT activity was mediated by increases in the steady-state level of its mRNA and immunodetectable protein. Using methyl donor-free diets, we found that methionine restriction was required but alone not sufficient for the high induction of BHMT expression. Concomitant with methionine restriction, dietary methyl groups were required for high levels of BHMT induction, and a dose-dependent relationship was observed between methyl donor intake and BHMT induction. Furthermore, the severity of methionine restriction influenced the magnitude of BHMT induction. To study the molecular mechanisms that regulate the expression of BHMT, we have cloned the human BHMT gene. This gene spans about 20 kilobases of DNA and contains 8 exons and 7 introns. Using RNA isolated from human liver and hepatoma cells, a major transcriptional start site has been mapped using the 5' rapid amplification of cDNA ends technique, and this start site is 26 nucleotides downstream from a putative TATA box. (+info)
Is whole grain intake associated with reduced total and cause-specific death rates in older women? The Iowa Women's Health Study.
(42/20742)
OBJECTIVES: This study sought to determine whether nutrient-rich whole grains reduce mortality risk. METHODS: The study included 38,740 Iowa women, aged 55 to 69 years. A food frequency questionnaire was used to obtain data on grain intake. RESULTS: Median whole grain intake quintiles ranged from a median of 0.2 to more than 3 servings per day. Women with higher intakes had healthier lifestyles and less baseline disease. The total death rate decreased in increasing quintiles, and the pattern repeated for cancer, cardiovascular disease, and other causes combined. Adjusted for lifestyle and baseline disease, the relative hazard rate ratio for total death was about 0.85 in daily consumers of whole grain. Findings persisted in strata of baseline healthy and diseased and were not explained by dietary fiber. Rates of total mortality, but not cardiovascular disease mortality, were higher among frequent consumers of refined grain. CONCLUSIONS: Total mortality risk was inversely associated with whole grain intake and positively associated with refined grain intake. Refined grains contributed more than 20% of energy intake, and whole grains contributed 1%. Substitution of whole for refined grain may reduce chronic disease risk in the United States. (+info)
A model of human phenylalanine metabolism in normal subjects and in phenylketonuric patients.
(43/20742)
The derivation of a quantitative model of phenylalanine metabolism in humans is described. The model is based on the kinetic properties of pure recombinant human phenylalanine hydroxylase and on estimates of the in vivo rates of phenylalanine transamination and protein degradation. Calculated values for the steady-state concentration of blood phenylalanine, rate of clearance of phenylalanine from the blood after an oral load of the amino acid, and dietary tolerance of phenylalanine all agree well with data from normal as well as from phenylketonuric patients and obligate heterozygotes. These calculated values may help in the decision about the degree of restriction of phenylalanine intake that is necessary to achieve a satisfactory clinical outcome in classical patients and in those with milder forms of the disease. (+info)
Onset of adolescent eating disorders: population based cohort study over 3 years.
(44/20742)
OBJECTIVE: To study the predictors of new eating disorders in an adolescent cohort. DESIGN: Cohort study over 3 years with six waves. SUBJECTS: Students, initially aged 14-15 years, from 44 secondary schools in the state of Victoria, Australia. OUTCOME MEASURES: Weight (kg), height (cm), dieting (adolescent dieting scale), psychiatric morbidity (revised clinical interview schedule), and eating disorder (branched eating disorders test). Eating disorder (partial syndrome) was defined when a subject met two criteria for either anorexia nervosa or bulimia nervosa according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). RESULTS: At the start of the study, 3.3% (29/888) of female subjects and 0.3% (2/811) of male subjects had partial syndromes of eating disorders. The rate of development of new eating disorder per 1000 person years of observation was 21.8 in female subjects and 6.0 in male subjects. Female subjects who dieted at a severe level were 18 times more likely to develop an eating disorder than those who did not diet, and female subjects who dieted at a moderate level were five times more likely to develop an eating disorder than those who did not diet. Psychiatric morbidity predicted the onset of eating disorder independently of dieting status so that those subjects in the highest morbidity category had an almost sevenfold increased risk of developing an eating disorder. After adjustment for earlier dieting and psychiatric morbidity, body mass index, extent of exercise, and sex were not predictive of new eating disorders. CONCLUSIONS: Dieting is the most important predictor of new eating disorders. Differences in the incidence of eating disorders between sexes were largely accounted for by the high rates of earlier dieting and psychiatric morbidity in the female subjects. In adolescents, controlling weight by exercise rather than diet restriction seems to carry less risk of development of eating disorders. (+info)
Dietary calcium phosphate stimulates intestinal lactobacilli and decreases the severity of a salmonella infection in rats.
(45/20742)
We have shown recently that dietary calcium phosphate (CaPi) has a trophic effect on the intestinal microflora and strongly protects against salmonella infection. It was speculated that precipitation by CaPi of intestinal surfactants, such as bile acids and fatty acids, reduced the cytotoxicity of intestinal contents and favored growth of the microflora. Because lactobacilli may have antagonistic activity against pathogens, the main purpose of the present study was to examine whether this CaPi-induced protection coincides with a reinforcement of the endogenous lactobacilli. In vitro, Salmonella enteritidis appeared to be insensitive to bile acids and fatty acids, whereas Lactobacillus acidophilus was killed by physiologically relevant concentrations of these surfactants. Additionally, after adaptation to a purified diet differing only in CaPi concentration (20 and 180 mmol CaHPO4. 2H2O/kg), rats (n = 8) were orally infected with S. enteritidis. Besides reducing the cytotoxicity and the concentration of bile acids and fatty acids of ileal contents and fecal water, CaPi notably changed the composition of ileal bile acids in a less cell-damaging direction. Significantly greater numbers of ileal and fecal lactobacilli were detected in noninfected, CaPi-supplemented rats. As judged by the lower urinary NOx excretion, which is a biomarker of intestinal bacterial translocation, dietary CaPi reduced the invasion of salmonella. Additionally, the colonization resistance was improved considering the reduction of excreted fecal salmonella. In accordance, fewer viable salmonella were detected in ileal contents and on the ileal mucosa in the CaPi group. In conclusion, reducing the intestinal surfactant concentration by dietary CaPi strengthens the endogenous lactobacilli and increases the resistance to salmonella. (+info)
Expression of T lymphocyte p56(lck), a zinc-finger signal transduction protein, is elevated by dietary zinc deficiency and diet restriction in mice.
(46/20742)
Compromised immune function is common to Zn deficiency, protein and energy malnutrition; however, the causative mechanisms at the molecular level have not been elucidated. The T lymphocyte signal transduction pathway contains several Zn-finger proteins, and it is possible that the in vivo functioning of these proteins could be affected by dietary deficiency of Zn and amino acids. Thus, the objective was to investigate the effects, on expression of the T lymphocyte signal transduction proteins p56(lck), phospholipase Cgamma1 (PLCgamma1) and protein kinase C (PKCalpha), of dietary Zn deficiency (ZnDF, < 1 mg Zn/kg diet) and protein-energy malnutrition syndromes [2% protein deficiency (LP), combined Zn and 2% protein deficiency (ZnDF+LP), and diet restriction (DR, body weight equal to ZnDF)] compared with control (C) mice. Indices of nutritional status and splenocyte counts were also determined. Based on serum albumin and liver lipid concentrations, the ZnDF+LP and LP groups had protein-type malnutrition, whereas the ZnDF and DR groups had energy-type malnutrition. For Western immunoblotting of the signal transduction proteins, mouse splenic T lymphocytes were isolated by immunocolumns. The expression of T lymphocyte p56(lck) was significantly elevated in the ZnDF+LP, ZnDF and DR groups compared to the C group. In contrast, the expression of PLCgamma1 and PKC was unaffected. There was a significant negative correlation between T lymphocyte p56(lck) expression and serum Zn (r= -0.65, P = 0.0007) or femur Zn (r = -0.73, P = 0.0001) concentrations. We propose that elevated T lymphocyte p56(lck) may contribute to altered thymoctye maturation, apoptosis and lymphopenia in Zn deficiency and protein-energy malnutrition syndromes. (+info)
Dietary pectin lowers sphingomyelin concentration in VLDL and raises hepatic sphingomyelinase activity in rats.
(47/20742)
There is evidence that cholesterol and sphingomyelin metabolism are interrelated, and thus the hypothesis tested was that dietary pectin, because it can alter hepatic cholesterol metabolism, would also alter hepatic sphingomyelin metabolism. For that purpose, 4-wk-old female Wistar rats were fed a diet without or with pectin (20 g/100 g) up to 21 d. In accordance with previous work, pectin consumption caused a significant (P < 0.001) reduction in hepatic (65%), whole plasma (37%), and VLDL (80%) cholesterol levels. Pectin also significantly reduced VLDL sphingomyelin concentrations (57%), but raised the amount of sphingomyelin in the high density lipoproteins (HDL)-2 fractions (58%), so that the level of sphingomyelin in whole plasma remained unaffected. Pectin did not affect the sphingomyelin concentration in the liver. Pectin consumption did not affect the hepatic sphingomyelin synthesizing enzymes, serine palmitoyltransferase, phosphatidylcholine:ceramide phosphocholine transferase, or phosphatidylethanolamine:ceramide phosphoethanolamine transferase. In contrast, dietary pectin activated both lysosomal (28%) and plasma membrane (26%) sphingomyelinase and thus may have enhanced sphingomyelin degradation. An attempt was made to describe the effects of dietary pectin on sphingomyelin metabolism in terms of altered fluxes through liver and plasma, with whole liver and whole plasma concentrations of sphingomyelin remaining unaffected. (+info)
Dietary thiamin level influences levels of its diphosphate form and thiamin-dependent enzymic activities of rat liver.
(48/20742)
This study was prompted by our incomplete understanding of the mechanism responsible for the clinical benefits of pharmacological doses of thiamin in some patients with maple syrup urine disease (MSUD) and the question of whether thiamin diphosphate (TDP), a potent inhibitor of the activity of the protein kinase that phosphorylates and inactivates the isolated branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex, affects the activity state of the complex. Rats were fed a chemically-defined diet containing graded levels of thiamin (0, 0.275, 0.55, 5.5, and 55 mg thiamin/kg diet). Maximal weight gain was attained over a 3-wk period only in rats fed diets with 5.5 and 55 mg thiamin/kg. Feeding rats the thiamin-free diet for just 2 d caused loss of nearly half of the TDP from liver mitochondria. Three more days caused over 70% loss, an additional 3 wk, over 90%. Starvation for 2 d had no effect, suggesting a mechanism for conservation of TDP in this nutritional state. Mitochondrial TDP was higher in rats fed pharmacological amounts of thiamin (55 mg thiamin/kg diet) than in rats fed adequate thiamin for maximal growth. Varying dietary thiamin had marked but opposite effects on the activities of alpha-ketoglutarate dehydrogenase (alpha-KGDH) and BCKDH. Thiamin deficiency decreased alpha-KGDH activity, increased BCKDH activity, and increased the proportion of BCKDH in the active, dephosphorylated, state. Excess dietary thiamin had the opposite effects. TDP appears to be more tightly associated with alpha-KGDH than BCKDH in thiamin-deficient rats, perhaps denoting retention of alpha-KGDH activity at the expense of BCKDH activity. Thus, thiamin deficiency and excess cause large changes in mitochondrial TDP levels that have a major influence on the activities of the keto acid dehydrogenase complexes. (+info)