Abstract 675: Contrasting Effects of Dietary Carbohydrate Compared to Mono-unsaturated Fat on Hepatic Production of ApoE and ApoC-III Containing VLDL, and Formation of LDL

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Chunyu Zheng ◽  
Christina Khoo ◽  
Frank M Sacks
Keyword(s):  
Dietary Intervention ◽  
Isotope Labeling ◽  
Lipoprotein Metabolism ◽  
Kinetic Studies ◽  
High Plasma ◽  
Dietary Carbohydrate ◽  
Unsaturated Fat ◽  
Downstream Effects ◽  
Mufa Diet ◽  
Secretion Rates

The effects of substituting dietary carbohydrate (CHO) with mono-unsaturated fat (MUFA) on plasma apoB metabolism were evaluated in 12 adults: 6 with normal and 6 with high plasma triglyceride levels. They consumed for 3 weeks each time a high CHO diet (48% complex CHO, 8% MUFA) and a high MUFA diet (31% complex CHO, 24% MUFA). ApoB100 kinetic studies were performed at the end of each dietary intervention using stable isotope labeling with a bolus and a primed continuous infusion. Multiple VLDL, IDL, and LDL fractions were prepared according to their apoE and apoC-III content. Compared to the CHO diet, the MUFA diet increased the percentage of VLDL and IDL secreted with both apoE and apoC-III (45% on MUFA vs. 14% on CHO, p < 0.01) and reduced the percentage of VLDL and IDL secreted without either apoE or apoC-III (MUFA 19% vs. CHO 40%, p = 0.02). Total liver secretion rates of apoB100 lipoproteins were similar between diets (MUFA 11.6 vs. CHO 11.3 mg·day −1 ·kg −1 , p = NS). The dietary change did not affect the fractional catabolic rates and flux patterns of the lipoproteins. On both diets, VLDL and IDL that had apoE were rapidly cleared from the circulation, limiting LDL formation; whereas lipoproteins that did not have apoE or apoCIII mostly underwent lipolysis with little direct clearance, and were the main precursors of LDL. As a result, increased secretion of VLDL and IDL containing apoE and apoC-III caused by the MUFA diet was associated with higher direct clearance and lower LDL production rates (p = 0.02 vs. CHO), while the CHO diet increased LDL production due to increased secretion of VLDL without apoE or apoC-III. In conclusion, our results reveal a strong dietary effect on the secretion pattern of apoB100 lipoproteins. Substituting dietary complex carbohydrate with mono-unsaturated fat selectively promotes liver secretion of VLDL and IDL containing both apoE and apoC-III while suppressing the secretion of VLDL and IDL without apoE or apoC-III. This leads to significant downstream effects on LDL formation due to differential effects of apoE and apoC-III on apoB lipoprotein metabolism, resulting in enhanced particle clearance and reduced LDL formation with the MUFA diet compared to the CHO diet.

Carbamazepine increases atherogenic lipoproteins: mechanism of action in male adults

2002 ◽  
Vol 282 (2) ◽  
pp. H704-H716 ◽  
Author(s):  
Susanne Brämswig ◽  
Anja Kerksiek ◽  
Thomas Sudhop ◽  
Claus Luers ◽  
Klaus Von Bergmann ◽  
...  
Keyword(s):  
Isotope Labeling ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Mevalonic Acid ◽  
Kinetic Studies ◽  
Low Density ◽  
Production Rates ◽  
Underlying Mechanisms ◽  
Cholesterol Precursors

Treatment with carbamazepine (CBZ) affects cholesterol concentrations, but little is known about the precise nature and underlying mechanisms of changes in lipoprotein metabolism. We investigated prospectively the effects of CBZ on lipid metabolism in normolipemic adults. In 21 healthy males, lipoprotein and noncholesterol sterol concentrations were measured before and during treatment with CBZ for 70 ± 18 days. Thirteen subjects underwent kinetic studies of apolipoprotein-B (ApoB) metabolism with the use of endogenous stable isotope labeling. Lipoprotein kinetic parameters were calculated by multicompartmental modeling. Significant increases in total cholesterol, in ApoB-containing lipoproteins [very-low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low-density lipoprotein (LDL)], and in triglycerides, but not in high-density lipoprotein (HDL), were observed. Lipoprotein particle composition remained unchanged. Mean fractional catabolic and production rates of ApoB-containing lipoproteins were not significantly different, although mean production rates of VLDL and IDL were substantially increased (+46 ± 139% and +30 ± 97%, respectively), whereas mean production of LDL remained unchanged (+2.1 ± 45.6%). Cholestanol in serum increased significantly but not the concentrations of plant sterols (campesterol, sitosterol) and the cholesterol precursors (lathosterol, mevalonic acid). There was a significant correlation between the decrease in free thyroxine and the increase in IDL cholesterol. Treatment with CBZ increases mainly ApoB-containing lipoproteins. CBZ seems not to influence endogenous cholesterol synthesis or intestinal absorption directly. The increase is neither related to increased ApoB production nor to decreased catabolism but is rather due to changes in the conversion cascade of IDL particles, most likely as an indirect effect through a decrease in thyroid hormones.

scholarly journals Pleiotropic Effects of Thyroid Hormones: Learning from Hypothyroidism

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Martha Franco ◽  
Edmundo Chávez ◽  
Oscar Pérez-Méndez
Keyword(s):  
Thyroid Hormones ◽  
Vascular Function ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Ldl Receptor ◽  
Lipoprotein Metabolism ◽  
Permeability Transition Pore ◽  
Hdl Cholesterol ◽  
Permeability Transition ◽  
High Plasma

Hypothyroidism induces several metabolic changes that allow understanding some physiopathological mechanisms. Under experimental hypothyroid conditions in rats, heart and kidney are protected against oxidative damage induced by ischemia reperfusion. An increased resistance to opening of the permeability transition pore seems to be at the basis of such protection. Moreover, glomerular filtration rate of hypothyroid kidney is low as a result of adenosine receptors-induced renal vasoconstriction. The vascular tone of aorta is also regulated by adenosine in hypothyroid conditions. In other context, thyroid hormones regulate lipoprotein metabolism. High plasma level of LDL cholesterol is a common feature in hypothyroidism, due to a low expression of the hepatic LDL receptor. In contrast, HDL-cholesterol plasma levels are variable in hypothyroidism; several proteins involved in HDL metabolism and structure are expressed at lower levels in experimental hypothyroidism. Based on the positive influence of thyroid hormones on lipoprotein metabolism, thyromimetic drugs are promising for the treatment of dyslipidemias. In summary, hypothyroid status has been useful to understand molecular mechanisms involved in ischemia reperfusion, regulation of vascular function and intravascular metabolism of lipoproteins.

scholarly journals Genomic Microdiversity of Bifidobacterium pseudocatenulatum Underlying Differential Strain-Level Responses to Dietary Carbohydrate Intervention

mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Guojun Wu ◽  
Chenhong Zhang ◽  
Huan Wu ◽  
Ruirui Wang ◽  
Jian Shen ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Human Health ◽  
Dietary Intervention ◽  
Genomic Diversity ◽  
Strain Level ◽  
Transport Systems ◽  
Gene Copy ◽  
Dietary Carbohydrate ◽  
A Genome ◽  
Differential Responses

ABSTRACT The genomic basis of the response to dietary intervention of human gut beneficial bacteria remains elusive, which hinders precise manipulation of the microbiota for human health. After receiving a dietary intervention enriched with nondigestible carbohydrates for 105 days, a genetically obese child with Prader-Willi syndrome lost 18.4% of his body weight and showed significant improvement in his bioclinical parameters. We obtained five isolates (C1, C15, C55, C62, and C95) of one of the most abundantly promoted beneficial species, Bifidobacterium pseudocatenulatum , from a postintervention fecal sample. Intriguingly, these five B. pseudocatenulatum strains showed differential responses during the dietary intervention. Two strains were largely unaffected, while the other three were promoted to different extents by the changes in dietary carbohydrate resources. The differential responses of these strains were consistent with their functional clustering based on the COGs (Clusters of Orthologous Groups), including those involved with the ABC-type sugar transport systems, suggesting that the strain-specific genomic variations may have contributed to the niche adaption. Particularly, B. pseudocatenulatum C15, which had the most diverse types and highest gene copy numbers of carbohydrate-active enzymes targeting plant polysaccharides, had the highest abundance after the dietary intervention. These studies show the importance of understanding genomic diversity of specific members of the gut microbiota if precise nutrition approaches are to be realized. IMPORTANCE The manipulation of the gut microbiota via dietary approaches is a promising option for improving human health. Our findings showed differential responses of multiple B. pseudocatenulatum strains isolated from the same habitat to the dietary intervention, as well as strain-specific correlations with bioclinical parameters of the host. The comparative genomics revealed a genome-level microdiversity of related functional genes, which may have contributed to these differences. These results highlight the necessity of understanding strain-level differences if precise manipulation of gut microbiota through dietary approaches is to be realized.

Cholesteryl ester transfer protein (CETP) increases postprandial triglyceridaemia and delays triacylglycerol plasma clearance in transgenic mice

2009 ◽  
Vol 419 (3) ◽  
pp. 629-634 ◽  
Author(s):  
Alessandro G. Salerno ◽  
Patrícia R. Patrício ◽  
Jairo A. Berti ◽  
Helena C. F. Oliveira
Keyword(s):  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Plasma Clearance ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Kinetic Studies ◽  
Cholesteryl Oleate ◽  
Liver Uptake ◽  
Transfer Protein

The CETP (cholesteryl ester transfer protein) is a plasma protein synthesized in several tissues, mainly in the liver; CETP reduces plasma HDL (high-density lipoprotein) cholesterol and increases the risk of atherosclerosis. The effect of CETP levels on postprandial intravascular metabolism of TAGs (triacylglycerols) is an often-overlooked aspect of the relationship between CETP and lipoprotein metabolism. Here, we tested the hypothesis that CETP delays the plasma clearance of TAG-rich lipoprotein by comparing human CETP expressing Tg (transgenic) and non-Tg mice. After an oral fat load, the postprandial triglyceridaemia curve was markedly increased in CETP-Tg compared with non-Tg mice (280±30 versus 190±20 mg/dl per 6 h respectively, P<0.02). No differences in intestinal fat absorption and VLDL (very-low-density lipoprotein) secretion rates were observed. Kinetic studies of double-labelled chylomicron-like EMs (emulsions) showed that both [3H]triolein and [14C]cholesteryl oleate FCRs (fractional clearance rates) were significantly reduced (∼20%) in CETP-Tg mice. Furthermore, TAG from lipid EM pre-incubated with CETP-Tg plasma had plasma clearance and liver uptake significantly lower than the non-Tg plasma-treated lipid EM. In addition, reductions in post-heparin plasma LPL (lipoprotein lipase) activity (50%) and adipose tissue mRNA abundance (39%) were verified in CETP-Tg mice. Therefore we conclude that CETP expression in Tg mice delays plasma clearance and liver uptake of TAG-rich lipoproteins by two mechanisms: (i) transferring TAG to HDLs and increasing CE content of the remnant particles and (ii) by diminishing LPL expression. These findings show that the level of CETP expression can influence the responsiveness to dietary fat and may lead to fat intolerance.

THE EXTRACTION OF OESTROGENS, AND THE RATE OF SECRETION OF OESTRONE AND OESTRADIOL-17β BY THE UTERUS IN THE PREGNANT SHEEP

1974 ◽  
Vol 61 (2) ◽  
pp. 277-284 ◽  
Author(s):  
J. R. G. CHALLIS ◽  
F. A. HARRISON ◽  
R. B. HEAP
Keyword(s):  
Jugular Vein ◽  
Kinetic Studies ◽  
Late Pregnancy ◽  
Peripheral Circulation ◽  
Gravid Uterus ◽  
Uterine Blood Flow ◽  
Pregnant Sheep ◽  
Tracer Kinetic ◽  
Arteriovenous Difference ◽  
Secretion Rates

SUMMARY The sharp increase in oestrone and oestradiol-17β production during the 48 h before parturition in the ewe does not always result in the uterine venous concentration of these steroids being greater than that found in peripheral blood, even though the gravid uterus is considered to be the major source of enhanced oestrogen synthesis in late pregnancy. This anomaly has been partly resolved by the results from tracer kinetic studies. During the infusion of labelled oestradiol-17β or oestrone into a jugular vein to steady state, 53% of [3H]oestradiol-17β and 62% of [3H]oestrone in the peripheral circulation were extracted by a gravid uterine horn. The extraction of [3H]oestradiol-17α, a product of the infused steroids, was 53% and 45% during the infusion of [3H]oestrone and [3H]oestradiol-17β, respectively. Calculations of the secretion rate of these steroids by one gravid horn, after correcting for uterine extraction, gave values that represented a substantial proportion of the kinetically determined production rate. This confirms that an appreciable part of the oestrogen produced just before term is in fact derived from the gravid uterus. However, the possibility that other sources may contribute to oestrogen synthesis in late pregnancy cannot be excluded. The findings show that a direct measurement of arteriovenous difference and uterine blood flow is inadequate to determine oestrogen secretion rates by the gravid uterus.

scholarly journals Agent-Based Modeling Predicts HDL-independent Pathway of Removal of Excess Surface Lipids from Very Low Density Lipoprotein

2018 ◽  
Author(s):  
Yared Paalvast ◽  
Jan Albert Kuivenhoven ◽  
Barbara M. Bakker ◽  
Albert .K. Groen
Keyword(s):  
Lipoprotein Metabolism ◽  
Hdl Cholesterol ◽  
High Plasma ◽  
Surface Lipid ◽  
Agent Based ◽  
Plasma Triglycerides ◽  
Excess Surface ◽  
Surface Lipids ◽  
Low Hdl ◽  
Experimental Findings

AbstractA hallmark of the metabolic syndrome is low HDL-cholesterol coupled with high plasma triglycerides (TG), but it is unclear what drives this close association. Plasma triglycerides and HDL cholesterol are thought to communicate through two distinct mechanisms. Firstly, excess surface lipids from VLDL released during lipolysis are transferred to HDL, thereby contributing to HDL directly but also indirectly through providing substrate for LCAT. Secondly, high plasma TG increases clearance of HDL through core-lipid exchange between VLDL and HDL via CETP and subsequent hydrolysis of the TG in HDL, resulting in smaller HDL and thus increased clearance rates.To test our understanding of how high plasma TG induces low HDL-cholesterol, making use of established knowledge, we developed a comprehensive agent-based model of lipoprotein metabolism which was validated using monogenic disorders of lipoprotein metabolism.By perturbing plasma TG in the model, we tested whether the current theoretical framework reproduces experimental findings. Interestingly, while increasing plasma TG through simulating decreased lipolysis of VLDL resulted in the expected decrease in HDL cholesterol, perturbing plasma TG through simulating increased VLDL production rates did not result in the expected HDL-TG relation at physiological lipid fluxes. However, model perturbations and experimental findings can be reconciled if we assume a pathway removing excess surface-lipid from VLDL that does not contribute to HDL cholesterol ester production through LCAT. In conclusion, our model simulations suggest that excess surface lipid from VLDL is cleared in part independently from HDL.Author summaryWhile it has long been known that high plasma triglycerides are associated with low HDL cholesterol, the reason for this association has remained unclear. One of the proposed mechanisms is that during catabolism of VLDL, lipoproteins rich in triglyceride, the excess surface of these particles become a source for the production of HDL cholesterol, and that therefore decreased catabolism of VLDL will lead to both higher plasma triglyceride and low HDL cholesterol. Another proposed mechanism is that during increased production of VLDL, there will be increased exchange of core lipids between VLDL and HDL, with subsequent hydrolysis of the triglyceride in HDL, leading to smaller HDL that is cleared more rapidly. To investigate these mechanisms further we developed a computational model based on established knowledge concerning lipoprotein metabolism and validated the model with known findings in monogenetic disorders. Upon perturbing the plasma triglycerides within the model by increasing the VLDL production rate, we unexpectedly found an increase in both triglyceride and HDL cholesterol. However, upon assuming that less excess surface lipid is available to HDL, HDL decreases in response to increased VLDL production. We therefore propose that there must be a pathway removing excess surface lipids that is independent from HDL.AbbreviationsPR(production rate)FCR(fractional catabolic rate)ppd(pool per day)SRB1(scavenger receptor B1)EL(endothelial lipase)HL(hepatic lipase)PLTP(phospholipid transfer protein)CETP(cholesteryl ester transfer protein)FC(free cholesterol)CE(cholesterol ester)PL(phospholipid)LpX(lipoprotein X).

scholarly journals The impact of a reduced calorie, macronutrient diet change on Caucasian males in relation to genotypes associated with obesity, increased BMI and dietary response

2018 ◽  
Author(s):  
L Ellis ◽  
C. Collins
Keyword(s):  
Dna Analysis ◽  
Dietary Intervention ◽  
Calorie Intake ◽  
Diet Change ◽  
Unsaturated Fat ◽  
Genetic Components ◽  
Diet Plan ◽  
To Come ◽  
The Impact ◽  
Diet And Lifestyle

AbstractObesity is a growing crisis within the 1st world and the causes of obesity are well studied: a lack of physical activity combined with an increased calorie intake. This energy imbalance leads to fat accumulation leading to eventual obesity. Whilst the cause may appear clear, the options of lifestyle change and/or diet planning that is efficient with effective sustainability has been harder to come by. Genetic variants linked to obesity may hold clues on how to best customise a diet plan to an individual leading to an easier to change lifestyle with better sustainability. This study aimed to find correlations with a diet change that decreased kcal intake by 200kcal per day with a macronutrient alteration (decreased carbohydrates and increased unsaturated fat) and genetic components to discover responders and non-responders. Within the study group of Caucasian males the genes TCF7L2, TFAP2B, PPARG2 and FTO all impacted the response of the dietary intervention. In conclusion it would be prudent to consider DNA analysis as part of a battery of diet and lifestyle tests to personalise a sustainable and effective lifestyle/dietary intervention to help control weight.

Interim analysis of a prospective randomized trial of dietary carbohydrate restriction for men with a rising PSA after failed primary treatment: Carbohydrate and Prostate Study 2 (CAPS2).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 382-382
Author(s):  
Stephen J. Freedland ◽  
Jenifer Allen ◽  
Andrew J. Armstrong ◽  
Judd W. Moul ◽  
Howard M. Sandler ◽  
...  
Keyword(s):  
Weight Loss ◽  
Interim Analysis ◽  
Dietary Intervention ◽  
Local Treatment ◽  
Carbohydrate Restriction ◽  
Dietary Carbohydrate ◽  
Carbohydrate Diet ◽  
Curative Intent ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate

382 Background: Nearly one third of men treated with curative intent for localized prostate cancer (PC) will develop a rising PSA. The rate of PSA rise (PSA doubling time aka PSASDT) is a predictor metastases and PC death. In laboratory mice, an extreme low carbohydrate diet slows PC growth. We tested whether this diet could slow PSADT in men with recurrent PC. Methods: We are conducting a 6-month multi-center randomized phase II trial of dietary carbohydrate restriction vs. no diet intervention control. Men had to have a BMI ≥24 kg/m2, received radical prostatectomy or definitive local radiation for PC, had a PSA 0.4-20.0 ng/ml (3-20 if prior radiation therapy) within the past 3 months, and current PSADT 3-36 months. The intervention arm was instructed to eat < 20 grams/carbs/day with no other limits. The control arm was told to make no diet. In this interim analysis, we present the efficacy of the dietary intervention with regards to weight loss. Arms were compared using rank-sum. Total anticipated enrollment is 60. The primary outcome is differences in PSADT between arms. Secondary outcomes include weight loss, and dietary make-up. Results: To date, 28 patients (14 in each study arm) have completed the study. Characteristics were well-balanced at baseline. At the 6-month dietary assessment, calorie consumption was similar between the two study arms (p = 0.090) among the 16 patients (7 low-carb, 9 control) with diet information. Subjects in the low-carb arm ate fewer carbs (29 vs. 188 g, p = 0.008) and more protein (125 vs. 73 g, p = 0.044) but similar amounts of fat (75 vs. 67 g, p = 0.672) vs. subjects in the control arm. Six months on the low carb diet resulted in greater weight loss (median: 31.7 vs. 0.8 lbs, p < 0.001), lower BMI (24.4 vs. 29.6 kg/m2, p < 0.001), and smaller waist circumference (95.7 vs. 108.9 cm, p = 0.002). Conclusions: In this interim analysis of an on-going dietary study for men with a rising PSA after definitive local treatment, an extreme low carbohydrate diet results in dramatic weight loss in 6 months. Whether this weight loss slows PC growth is an on-going question. Clinical trial information: NCT01763944.

Lipoprotein transport in the metabolic syndrome: methodological aspects of stable isotope kinetic studies

2004 ◽  
Vol 107 (3) ◽  
pp. 221-232 ◽  
Author(s):  
Dick C. CHAN ◽  
P. Hugh R. BARRETT ◽  
Gerald F. WATTS
Keyword(s):  
Metabolic Syndrome ◽  
Stable Isotope ◽  
Plasma Concentrations ◽  
Lipoprotein Metabolism ◽  
Visceral Obesity ◽  
Kinetic Studies ◽  
Kinetic Properties ◽  
The Metabolic Syndrome ◽  
Methodological Aspects

The metabolic syndrome encapsulates visceral obesity, insulin resistance, diabetes, hypertension and dyslipidaemia. Dyslipidaemia is a cardinal feature of the metabolic syndrome that accelerates the risk of cardiovascular disease. It is usually characterized by high plasma concentrations of triacylglycerol (triglyceride)-rich and apoB (apolipoprotein B)-containing lipoproteins, with depressed concentrations of HDL (high-density lipoprotein). However, lipoprotein metabolism is complex and abnormal plasma concentrations can result from alterations in the rates of production and/or catabolism of these lipoprotein particles. Our in vivo understanding of kinetic defects in lipoprotein metabolism in the metabolic syndrome has been achieved chiefly by ongoing developments in the use of stable isotope tracers and mathematical modelling. This review deals with the methodological aspects of stable isotope kinetic studies. The design of in vivo turnover studies requires considerations related to stable isotope tracer administration, duration of sampling protocol and interpretation of tracer data, all of which are critically dependent on the kinetic properties of the lipoproteins under investigation. Such models provide novel insight that further understanding of metabolic disorders and effects of treatments. Future investigations of the pathophysiology and therapy of the dyslipoproteinaemia of the metabolic syndrome will require the development of novel kinetic methodologies. Specifically, new stable isotope techniques are required for investigating in vivo the turnover of the HDL subpopulation of particles, as well as the cellular efflux of cholesterol into the extracellular space and its subsequent transport in plasma and metabolic fate in the liver.

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