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Cadmium toxicity studies under long term-low level exposure (LLE) conditions. I. Metabolic patterns in rats exposed to present environmental dietary levels of Cd for two years.

A long term-low level exposure (LLE) experiment was conducted on rats to determine the metabolic patterns for realistic environmental dietary levels of cadmium. Male rats fed with 61 ppb of cadmium ad libitum, 50 labelled with 109 Cd radiotracer as cadmium chloride via drinking mineral water and 11 unlabelled via food for 2 years. The diet was characterized in its metal content by neutron activation analysis to obtain the total dietary intake of different elements. The kidney was found to be the tissue with the major concentration of cadmium which accumulated continuously during the experiment. The variation of the accumulation pattern of Cd concentration in the liver and intestine indicated an itiial rapid increase of Cd during the first 100 days. After this period an apparent equilibrium was attained in both these tissues until the end of the study. The intracellular distribution of cadmium in kidneys, liver, intestine and pancreas were similar, the cytosol fractions containing about 80% of the cellular cadmium. Dialysis experiments indicated that significant amounts of cadmium were able to be associated with cellular organelles, the mitochondria representing the most important organelle capable of binding cadmium. The cytoplasmatic Cd-profiles obtained at various stages of the experiment showed that the metal was only bound to a low-molecular-weight component, cadmium-binding protein (CdBP), which represents the specific cellular-binding component for cadmium under the long term-low level exposure (LLE) conditions. No significant variations in the concentrations of the elements in different organs were observed in animals supplemented with 109Cd untreated controls.

Animals

Insulinemic and inflammatory dietary patterns and colorectal cancer risk: a dietary data harmonization study of one million participants in the Consortium of Metabolomics Studies (COMETS).

BACKGROUND: Inflammatory and insulinemic dietary patterns have been associated with colorectal cancer (CRC) risk, but generalizability across diverse populations with heterogeneous food supplies and dietary behaviors has not been established. OBJECTIVES: We harmonized disparate dietary and covariate data on a large scale to compute the reverse Empirical Dietary Index for Hyperinsulinemia (rEDIH), reverse Empirical Dietary Inflammatory Pattern (rEDIP), and Healthy Eating Index (HEI)-2015 scores, and tested their associations with CRC risk. METHODS: We leveraged data among 501,892 women and 407,390 men from 6 cohorts across the United States (NIH-AARP, Multi-Ethnic Study of Atherosclerosis, Prostate, Lung, Colorectal, and Ovarian, SCCS) and Europe (EPIC, ATBC) with varying sociodemographic characteristics, participating in the Consortium of Metabolomics Studies. We harmonized nomenclature and nutritional information of >800 unique food items across cohorts. We used multivariable-adjusted Cox regression, adjusting for demographic, clinical, and lifestyle factors, to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between the dietary indices and CRC risk per cohort, then meta-analyzed the estimates. RESULTS: During a median follow-up of 14.9 y, 16,525 incident CRC cases were diagnosed. Participants in the highest quintile of rEDIH (low-insulinemic diet) had an 18% reduced risk of CRC (HR: 0.82; 95% CI: 0.78, 0.86) compared with those in the lowest quintile. For the same comparison, similar risk reductions were observed for rEDIP (anti-inflammatory diet) (HR: 0.84; 95% CI: 0.80, 0.89) and HEI-2015 (overall dietary quality) (HR: 0.80; 95% CI: 0.76, 0.85). Heterogeneity between cohorts in the meta-analyzed estimates was low for rEDIH (I2 = 22.3%) compared with rEDIP (I2 = 62.5%) and HEI-2015 (I2=83.9%). CONCLUSIONS: Using carefully harmonized data from nearly 1 million individuals in the United States and Europe, we observed significant CRC risk reduction with habitual intake of low-insulinemic and anti-inflammatory dietary patterns, comparable with higher overall dietary quality. Study findings underscore the utility of these dietary patterns for global cancer prevention efforts.

Humans

Gut bacteria associated with an atherogenic TMAO-dietary pattern and choline-rich foods among aging women.

BACKGROUND AND AIMS: Choline can be metabolized by gut bacteria with a choline utilization gene, CutC, as identified through genome sequencing studies. This metabolism produces trimethylamine, the precursor to the atherosclerotic metabolite trimethylamine N-oxide (TMAO). Bacterial species involved in trimethylamine production in free-living humans have been under-investigated. We previously developed the TMAO dietary pattern (TMAO-DP), which is predictive of plasma TMAO and choline. We evaluated associations between the TMAO-DP, dietary choline, and choline-rich foods (fish, red meat, eggs) with the abundance of species with CutC. We also explored associations between the TMAO-DP and microbiome diversity. METHODS AND RESULTS: This cross-sectional analysis included 287 women (mean age = 79.6 years) from the Women's Health Initiative. Diet was assessed using a food frequency questionnaire. Stool samples were collected and the V3-V4 regions of the 16S ribosomal RNA were sequenced. Adjusted linear regression models evaluated associations between the TMAO-DP with the CLR-transformed abundance of species with CutC and with alpha-diversity indices. For beta-diversity, PERMANOVA examined measures of Aitchison distance within and between quartiles of the TMAO-DP. Associations between dietary choline and choline-rich foods with the abundance of species were evaluated using linear regression. The TMAO-DP was associated with Acidaminococcus intestini [Beta (SE): 0.23 (0.09), p-value = 0.035] and Desulfovibrio desulfuricans [Beta (SE): 0.16 (0.6), p = 0.035]. The TMAO-DP was not associated with alpha- or beta-diversity. CONCLUSION: This study provides evidence that Desulfovibrio desulfuricans and Acidaminococcus intestini, two species identified as having CutC by gene sequencing, may produce trimethylamine from diet in free-living women.

Humans

Diet modulates cardiac metabolic stress during anthracycline treatment.

Diet is a modifiable determinant of cardiovascular risk and may influence tolerance to cancer therapies. The mechanisms by which specific dietary components affect cardiac metabolism during anthracycline treatment remain poorly defined, limiting the incorporation of dietary recommendations into treatment guidelines. Here, we integrated heart proteomics data from patients treated with or without anthracyclines with a genome-scale reconstruction of human cardiac metabolism (CardioNet). Using constraint-based flux analysis, we conducted >30,000 in silico simulations of diet scenarios generated from chemical profiles of ∼500 foods curated in the Periodic Table of Food Initiative. These simulations revealed that diets enriched in rapidly absorbable sugars and depleted of essential fatty acids impair cardiac metabolic efficiency, increasing reactive oxygen species production and the demand for purine salvage fluxes. These predicted metabolic patterns were consistent with plasma metabolomics from patients treated with anthracyclines, validating our findings. Computational modeling of 39 recipes across six cuisines revealed cardiometabolic effects of omnivorous versus vegan diets in patients. Modeling of a healthy vegan diet increased cardiometabolic efficiency compared with a healthy omnivorous diet in patients treated with anthracyclines, independent of the culinary background. Our approach demonstrates that integrating the molecular composition of food with genome-scale metabolic models enables systematic analysis of diet patterns for translational testing. Ultimately, these in silico studies provide a framework for trials and may inform dietary recommendations for improving cardiometabolic health.NEW & NOTEWORTHY We developed a systems biology framework to predict how diet influences cardiac metabolism during cancer therapy. Across >30,000 in silico diet simulations, we identified nutrient patterns that either exacerbate or mitigate anthracycline-induced metabolic stress. These findings demonstrate how computational modeling can uncover diet-metabolism interactions driving cardiotoxicity and guide dietary interventions.

Humans

Arrhythmia and cardiomyopathy risk in Taiwan with complementary biobank evidence on thyroid genetic susceptibility: an integrative population-based framework.

BACKGROUND: Arrhythmia-induced cardiomyopathy (AiCM) is a potentially reversible cause of ventricular dysfunction; however, only a subset of patients with arrhythmia develop cardiomyopathy. Emerging evidence suggests that endocrine factors, particularly thyroid dysfunction with genetic susceptibility, may contribute to inter-individual variability in arrhythmia-related myocardial outcomes. METHODS: We performed a dual-cohort population-based study using the National Health Insurance Research Database (NHIRD, 2000-2015) and the Taiwan Biobank (TWB). In NHIRD, we examined the association between newly diagnosed arrhythmia and incident cardiomyopathy using Cox proportional hazards models. In TWB, genome-wide data, thyroid-stimulating hormone (TSH), polygenic risk scores (PRSs), lifestyle factors, and metabolic comorbidities were analyzed using multivariable regression and interaction models to assess determinants of thyroid dysfunction. RESULTS: In the NHIRD cohort, arrhythmia was associated with a significantly increased risk of incident cardiomyopathy (adjusted hazard ratio (aHR): 2.49, 95% CI: 1.94-2.96), with atrial fibrillation showing the strongest association among arrhythmia subtypes. In the TWB cohort, a higher thyroid polygenic risk score was strongly associated with thyroid dysfunction (adjusted odds ratio (aOR): 6.64, 95% CI: 5.86-7.52). The association between genetic susceptibility and thyroid dysfunction was further modified by metabolic and lifestyle factors, including diabetes, hyperlipidemia, and dietary patterns. Genome-wide analysis identified multiple loci associated with thyroid-stimulating hormone regulation, consistent with a polygenic architecture of thyroid endocrine traits. CONCLUSION: Arrhythmia was associated with an increased risk of cardiomyopathy in a nationwide cohort, while thyroid genetic susceptibility was strongly associated with thyroid dysfunction in a biobank cohort and modified by metabolic and lifestyle factors. These findings provide complementary population-level evidence of parallel cardiovascular and endocrine-genetic associations. Because the two cohorts were not individually linked, causal inference cannot be established. The results support a systems-level framework of endocrine-cardiac interaction and suggest that integrated clinical and genetic risk assessment may help identify individuals who warrant closer monitoring.

arrhythmia

Breathing in the potassium depleted rat: the role of metabolic rate and body temperature.

Rats with dietary potassium (K) depletion have an altered breathing pattern compared to age matched control rats. The K depleted rats also have a decreased body weight gain, basal metabolic rate and body temperature. In this study, age matched controls are underfed (UFC) to match for body weight gain and metabolic rate and controls are exposed to different ambient temperatures to alter metabolism and body temperature. Compared to UFC rats with the same body weight and basal metabolic rate the K depleted rats breathe slower and with a larger tidal volume in the basal state and in response to hypercapnia and hypoxia. With heat stress body temperature is increased in K depleted rats as is metabolic rate. While frequency is increased it is still slower than in controls at the same ambient and body temperatures. We conclude that the low metabolic rate and body temperature of K depleted rats is not the cause of the altered breathing pattern. In addition, it is shown that the hypothermia of K depletion is present only at ambient temperatures below the thermoneutral zone and that is is apparently due to an inability of the K depleted rat to increase metabolic heat production with cold stress.

Animals

Nutrition and longevity - diet in centenarians.

BACKGROUND: Nutrition plays a central role in the biological mechanisms that shape aging, health span, and longevity. Micronutrients—including vitamins, trace elements, and polyphenols—support genomic stability, mitochondrial integrity, and antioxidant defense, while dietary patterns rich in plant-based foods modulate inflammation, metabolic regulation, and epigenetic processes. Centenarian populations consuming Mediterranean, Okinawan, Nordic, and Nicoyan diets offer a natural model for understanding how nutrient-rich, minimally processed foods, moderate caloric intake, and balanced lifestyles interact with molecular pathways to extend functional life. MAIN BODY: This review synthesizes current evidence on how micronutrients influence DNA repair, oxidative stress reduction, and mitochondrial protection, particularly through the actions of vitamins C and E, niacin-dependent PARP activity, folate-mediated methylation, and metal cofactors involved in antioxidant enzymes. Plant-based diets rich in fiber and polyphenols enhance microbial diversity and promote beneficial taxa such as Akkermansia and Bifidobacterium, supporting gut barrier integrity and immune balance. Caloric restriction and intermittent fasting activate nutrient-sensing pathways, including AMPK and sirtuins, reduce mTOR activity, and stimulate autophagy, collectively improving cellular resilience. Findings from centenarian regions highlight the convergence of lifestyle, nutrition, and cultural practices that reduce systemic inflammation, maintain metabolic flexibility, and support healthy aging trajectories. CONCLUSIONS: Diet emerges as a decisive modifiable determinant of lifespan and health span. The convergence of molecular nutrition, microbiome composition, and traditional dietary habits underlies the exceptional longevity observed in centenarian populations. Future research should integrate nutrigenomics, metabolomics, and microbiome profiling to clarify causal mechanisms and guide precision nutrition strategies for aging societies.

Humans

Dietary lipid metabolism in lactating dairy cows.

Effects of feeding an oil seed supplement treated with formalin upon lipid patterns of blood and synthesis of milk fat were evaluated. Percentages and yields of fatty acids of milk fat with chain lengths between 6 and 16 carbons were decreased while percentages and yields of stearate and linoleate were increased when the lipid supplement was fed. Calculations in cows fed control and supplement, 60% and 80%, respectively, of fatty acids of milk were derived from lipids of blood were supported by arterial-venous differences. Comparisons of the fatty acid compositions of triacylglycerol of plasma and milk fat suggested that triacylglycerol may not be the sole source of linoleate transferred from blood to milk fat. A preliminary evaluation of supplement effects upon lipoprotein patterns of serum indicated two peaks in the low density lipoprotein class and that the increase in total cholesterol of blood caused by feeding lipid supplement is due to increases in cholesterol content of the low density and high density lipoprotein classes.

Animals

Amino acid profiles, aging, and sex hormone interactions in the elderly Iranian population: a metabolomics study.

BACKGROUND: Aging and sex hormones significantly influences on metabolic profiles, particularly in individuals aged 50 year and older. This study aimed to investigate the associations between serum metabolites, aging, and sex hormone levels among elderly individuals in Bushehr, Iran - a coastal region characterized by a unique lifestyle, dietary patterns, and environmental conditions, such as high seafood consumption and exposure to marine climate, which may collectively influence metabolic profiles and hormone levels in the aging population. METHODS: This cross-sectional study analyzed data from the Bushehr Elderly Health Program, which included 2001 participants (1143 women and 858 men) aged over 50 years old from Bushehr, Iran. Serum levels of 20 amino acids were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the results were analyzed based on gender, age, menopause status, menopause age, and serum levels of sex hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol (E2). Statistical analyses were performed using SPSS version 25.0 and R version 4.0.3, with a focus on gender differences and the correlation between aging, sex hormones, and metabolite profiles. RESULTS: Among the 2001 participants, mean ages were 61.57 ± 7.6 years for women and 62.92 ± 8.4 years for men. Men had higher serum levels of glutamic acid, leucine, methionine, phenylalanine, tyrosine, valine, citrulline, ornithine, proline, threonine, histidine, lysine, tryptophan, asparagine, and glutamine, while women had higher levels of glycine and serine. Aging was associated with notable changes in amino acid levels, such as increased citrulline and decreased threonine in women, and similar trends in men with a pronounced decrease in alanine. In men, low testosterone levels were linked to reduced concentration of alanine, methionine, phenylalanine, tyrosine, citrulline, glycine ornithine, serine, lysine, asparagine, and glutamine. Postmenopausal women showed a significant decrease in threonine levels. DISCUSSION: The findings highlight the complex interplay between aging, sex hormones, and metabolic changes. Gender-specific differences in amino acid profiles suggest that sex hormones play a pivotal role in modulating metabolism, which may influence susceptibility to metabolic disorders. These insights could inform the development of targeted interventions tailored to the specific needs of aging populations. Future research should investigate the underlying mechanisms linking sex hormones to metabolic pathways and assess their potential for improving health outcomes in older adults.

Aging

Some features of glycogen metabolism in human skeletal muscle.

The higher the exercise intensity, the greater the relative proportion of energy output derived from carbohydrate metabolism. Muscle glycogen stores are the most important source of carbohydrate during heavy exercise and in normal dietary conditions. At the same relative energy output, a muscle rich in type II fibers obtains a relatively larger energy contribution from carbohydrates, in terms of local muscle glycogen utilization, than one rich in type I fibers. This pattern can be modified by different dietary means.

Dietary Carbohydrates

Trans fatty acids: positional specificity in brain lecithin.

Fifteen-day-old rats were divided into three groups: one group received an intracerebral injection of 5 microCi of 9-trans,12-trans [1-(14)C] octadecadienoic acid; the second group was given 5 microCi of the same compound plus an equal wt of nonradioactive all cis arachidonic acid; the third group was given 5 microCi of 9-trans [1-(14)C] octadecenoic acid. All animals were sacrificed 8 hr after injection. Glycerophosphocholine (GPC) was isolated and partically deacylated with phospholipase A2 from Crotalus Adamanteus venom. The results of this study were as follows: 1) after t[1-(14)C]18:1 injection, there was twice as much radioactivity in the 1-position as in the 2-position; 2) when tt[1-(14)C] 18:2 was injected, more than 90% of the total radioactivity was found in the 2-position; 3) following tt[1-(14)C]-18:2 + nonradioactive arachidonate injection, ca. 75% of the total radioactivity still remained in the 2-position; and 4) all of the injected [1-(14)C]-tracers showed evidence of undergoing beta-oxidation to form acetyl-CoA, which was converted to radioactive palmitate. The possibility is discussed that the observed distribution pattern of the injected radioactive tracers may be attributed to tissue metabolic specificity. Ramifications of the deposition of dietary trans fatty acids in the brain during the developmental stage of the central nervous system are also discussed.

Animals

Metabolic epidemiology of large bowel cancer: fecal bulk and constituents of high-risk North American and low-risk Finnish population.

The dietary pattern and fecal constituents of two populations with distinct risk for the development of colon cancer, a high-risk population in New York Metropolitan area and a low-risk population in rural Kuopio, were studied. The average daily intake of dietary fat and protein was the same in the two groups, but the sources of fat were different, a greater portion coming from dairy products in rural Kuopio and from meat in the New York Metropolitan area. Not only the frequency of bowel movements was higher, but also the daily total stool output as well as the fecal fiber excretion were greater in Kuopio compared with New York due to high dietary intake in rural Kuopio of cereal products rich in fiber. The concentration of fecal secondary bile acids and bacterial beta-glucuronidase activity was lower in rural Kuopio, but the total daily excretion of these constituents was the same in two populations. The daily fecal excretion of bacterial nuclear dehydrogenase activity and of neutral sterols was higher in rural Kuopio, and the concentration of these constituents was the same in the two groups. The high daily excretion of cholesterol metabolites in Kuopio might be due to high dietary intake of dairy products. The data suggest that one of the factors contributing to the low-risk of large bowel cancer in Finland, in spite of high dietary intake of fat, appears to be the fact that a high dietary fiber leads to an increase in stool bulk, thus diluting bile acids, which have promoting activity.

Bile Acids and Salts

Defective essential-fatty-acid metabolism in cystic fibrosis.

Cystic fibrosis (C.F.) is characterised by low serum levels of essential fatty acids (E.F.A.). However, the fatty-acid pattern does not totally resemble that of dietary E.F.A. deficiency. The differences suggest a reduction in the desaturation of E.F.S. It is not known whether this defect is the primary lesion in C.F. or is the result of tissue damage in the disease. It is proposed that C.F. patients might have increased linoleic-acid requirements, and possibly specific requirements for its desaturation products.

Animals

Adaptive Evolution of the PFK Gene Family in Chinese Longsnout Catfish, Leiocassis longirostris.

The Chinese longsnout catfish is a typical carnivorous fish with a relatively weak ability to utilize glucose. However, the genomic basis for its glucose metabolic adaptation remains unclear. In this study, we used comparative genomics methods to systematically analyze the evolutionary characteristics of glucose metabolism-related genes in the Chinese longsnout catfish, focusing on gene family evolution, patterns of expansion and contraction, and selective pressures. The results indicate that glucose metabolism-related genes have undergone significant reshaping during evolution. Genes involved in glucose digestion, absorption, and insulin signaling pathways demonstrate a tendency toward contraction, while those associated with protein and lipid metabolism exhibit expansion. This pattern is consistent with the species' long-term adaptation to a high-protein, high-fat diet. Comparative analysis further revealed that, compared to fish with different dietary habits, certain key genes involved in glycolysis in the Chinese longsnout catfish exhibit a reduction in copy number. Molecular evolutionary analysis showed that key genes involved in glycolysis and gluconeogenesis (including hexokinase 2 (hk2), phosphofructokinase, muscle/platelet (pfkm/p)) exhibit signs of accelerated evolution or positive selection. Notably, the PFK gene family exhibits complex evolutionary characteristics resulting from the combined effects of gene contraction, rapid evolution, and positive selection. In summary, this study reveals the genomic evolutionary basis for the glucose metabolic adaptation of the Chinese longsnout catfish and identifies the PFK gene family as a key candidate for elucidating its unique glucose metabolic characteristics.

Leiocassis longirostris

Influence of diets high and low in animal fat on bowel habit, gastrointestinal transit time, fecal microflora, bile acid, and fat excretion.

Epidemiological observations and animal experiments suggest that large bowel cancer is related to serveral factors. Among them, high dietary intakes of animal fat, the presence in the colon of relatively high levels of bile acids, specific patterns of intestinal microflora, slow transit through the gut, and low stool weights. Under metabolic conditions we have observed the effect on these variables of dietes containing 62 or 152 g/day of fat mainly of animal origin in six healthy young men over 4-wk periods. No change attributable to the diet was observed in the subjects' bowel habit, fecal weight, mean transit time through the gut, or in the excretion of dry matter. Total fecal bile acid excretion was significantly higher on the high fat diet (320 +/- 120 mg/day) than on the low fat diet (139.7) +/- 63 mg/day) t test = 7.78 P less than 0.001 as also was the total fecal fatty acid excretion, 3.1+/-0.71 and 1.14+/-0.35 g/day, respectively t test = 11.4 P less than 0.001). The fecal microflora including the nuclear dehydrogenating clostridia were unaltered by the dietary changes as was fecal beta-glucuronidase activity. Dietary changes which increase animal fat intake clearly influence fecal bile acid excretion in a way that would favor the development of large bowel cancer if current theories prove to be true. Dietary fat however has no effect on overall colonic function so other components of the diet must be responsible for the observed associations of bowel cancer with slow transit and reduced fecal bulk.

Adult

Forensic aspects of trace element variation in the hair of isolated Amazonas Indian tribes.

Thermal neutron activation analysis and instrumental gamma-ray spectrometry were used to analyze the elemental constituents in the head hair from sedentary Indian populations in the Venezuelan Amazonas region. Concentration values for 30 elements were determined quantitatively, and the presence of 7 others was detected qualitatively. The remoteness of the area and the primitive ecological conditions of the local population prevents the exposure of their biological systems to industrial and agricultural contamination, either external or metabolic. These conditions are reflected in a marked decrease of the concentration ranges of the trace elements, and a significant reduction or even the total absence of some components. The results demonstrate that closed groups of individuals exposed to similar dietary and environmental conditions exhibit closely similar trace element patterns in their hair and, consequently, in other biological tissue. This fact severely limits the use of trace element patterns in hair for forensic comparisons. The results also indicate that a large part of the constituents found in hair is probably deposited externally from ambient contamination and that any metabolic deposition occurs much more uniformly and probably in lower concentrations. Tables of analytical results in parts per million are presented, together with representative gamma-ray spectra of the hair. Comparison with earlier data in the literature is also shown.

Hair

The influence of dietary sulphur, molybdate and copper on the absorption, excretion and plasma fraction levels of 99Mo in sheep.

The effect of increased dietary sulphur, copper and molybdate on the metabolism of 99Mo administered via the rumen or duodenum was examined. Duodenally administered 99MoO4= was efficiently and rapidly absorbed and excreted via the urine; dietary modifications did not alter this pattern although increased dietary S increased the excretion rate. The passge of 99MoO4= through the rumen led to chemical modification, so that, particularly at high S levels, most of the radioactivity remained in the feces; increased dietary Mo led to increased absorption whereas increased copper decreased absorption. Incorportion of radioactivity into the TCA insoluble plasma fraction was shown with increased dietary S and particularly when both dietary S and Mo were increased. The compatiblity of the results with the hypothesis of ruminal thiomolybdate formation and subsequent reaction with dietary or tissue copper is discussed.

Animals

Bile acid kinetics in relation to endogenous tryglyceride metabolism in various types of hyperlipoproteinemia.

Bile acid and plasma endogenous triglyceride kinetics were determined under standardized dietary conditions in 47 hyperlipidemic subjects with the aid of [14C]cholic acid, [14C]chenodeoxycholic acid, and [3H]glycerol, respectively. On the basis of their lipoprotein pattern the patients were separated into three groups characterized by hyperlipoproteinemia (HLP) type IIa (n = 19), type IIb (n = 6), and type IV (n = 22). In keeping with previous reports from this laboratory the total bile acid formation reports from this laboratory the total bile acid formation in HLP type IV (19.5 +/- 2.2) mumol kg-1d-1, mean +/- SEM) exceeded that encountered in type IIa (10.7 +/- 0.9 mumol kg-1d-1, P less than 0.005). This difference was mainly due to an increased synthesis of cholic acid in type IV HLP (12.7 +/- 1.7 mumol kg-1d-1 vs. 6.1 +/- 0.5 mumol kg-1d-1, P less than 0.005). Bile acid formation in type IIb HLP was essentially within the limits recorded for type IIa. Apparent plasma triglyceride formation (as calculated from the 10-hr radioactivity decay curve) averaged 10.5 +/- 0.7 mumol kg-1hr-1 in type IIa HLP and was significantly higher in type IIb (20.7 +/- 1.9 mumol kg-1hr-1, P less than 0.001) and in type IV (22.1 +/- 1.4 mumol kg-1hr-1, P less than 0.001). The apparent fractional turnover rate of plasma triglyceride in type IV HLP (0.147 +/- 0.011 hr-1) was lower than that encountered in type IIa (0.188 +/- 0.008, P less than 0.01) and in type IIb (0.177 +/- 0.011 hr-1). The apparent production of plasma triglycerides and the formation of cholic acid correlated in type IIa (r = +0.69, P less than 0.001) and in type IV HLP (r = +0.70, P less than 0.001). A similar pattern was seen for total bile acid formation, while chenodeoxycholic acid showed a correlation to apparent triglyceride synthesis only in type IV HLP. It is suggested that an increased formation of plasma triglycerides--monitoring very low density lipoprotein synthesis--is linked to an enhanced degradation of cholesterol to bile acids and that there is an integrated regulation of the metabolism of these two parameters.

Adult