scholarly journals Effects of inulin-type fructans on lipid metabolism in man and in animal models

2005 ◽  
Vol 93 (S1) ◽  
pp. S163-S168 ◽  
Author(s):  
Michel Beylot

Studies in rodents show that inulin and oligofructose can reduce the plasma levels of cholesterol and triacylglycerols (TG). In addition, they can oppose TG accumulation in liver and have favourable effects on hepatic steatosis. The hypotriglyceridaemic effect is due to a reduction in hepatic re-esterification of fatty acids, but mainly in the expression and activity of liver lipogenesis, resulting in lower hepatic secretion rate of TG. This repression of lipogenesis is not observed in adipose tissue. The effect on liver lipogenesis can be explained by reduced insulin/glucose levels or by a selective exposure of the liver to increased amounts of propionic acid produced in the large intestine during fermentation of non-digestible carbohydrates. The decrease in plasma cholesterol could also be due to inhibition of cholesterol synthesis by propionic acid or to modifications in the bile acid metabolism. Studies in man yield more conflicting results with a decrease or no effects on plasma lipid levels, and, when a decrease is observed, more marked effects on TG than on cholesterol and more consistent action of inulin than of oligofructose. Besides the difference in the dose of inulin or oligofructose used, differences in metabolic status could play a role in this discrepancy between man and animals since reduction in plasma TG is observed in man mainly in a situation of increased liver lipogenesis (high-carbohydrate diet, obesity, hypertriglyceridaemia). The effects on plasma cholesterol appear also more marked in hyperlipidaemic subjects than in healthy controls, suggesting that inulin and oligofructose have beneficial effects in these types of subjects.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jonna Weisell ◽  
Anna-Kaisa Ruotsalainen ◽  
Juha Näpänkangas ◽  
Matti Jauhiainen ◽  
Jaana Rysä

AbstractIn calcific aortic valve disease (CAVD) progressive valvular calcification causes aortic valve dysfunction. CAVD has several risk factors such as age and dyslipidemia. Vitamin K was shown to inhibit vascular calcification in mice and valvular calcification in patients with CAVD. We studied the effect of menaquinone 4 (MK4/vitamin K2) on valvular calcification in the hypercholesterolemic mouse model of CAVD. LDLr−/−ApoB100/100 male mice were fed with a Western diet for 5 months, with (n = 10) or without (n = 10) added 0.2 mg/g MK4. Body weight gain was followed weekly. Morphology of aortic valves and liver was assessed with immunohistochemistry. Plasma cholesterol levels and cytokines from hepatic tissue were assessed in the end of the study. Hepatic gene expression of lipid metabolism regulating genes were assessed after 18 h diet. MK4 exacerbated the lipoprotein lipid profile without affecting aortic valve morphology in hypercholesterolemic LDLr−/− ApoB100/100 mice. The MK4-containing WD diet increased plasma levels of LDL and triglycerides, hepatic steatosis, and mRNA expression of genes required for triglyceride and cholesterol synthesis. MK4 diminished levels of several cytokines and chemokines in liver, including IL-6, TNFα and MCP1, as measured by hepatic cytokine array. Consequently, MK4 may exert non-beneficial effects on circulating lipid levels, especially in hypercholesterolemic individuals.


2010 ◽  
Vol 104 (3) ◽  
pp. 364-373 ◽  
Author(s):  
Tina Immerstrand ◽  
Kristina E. Andersson ◽  
Caroline Wange ◽  
Ana Rascon ◽  
Per Hellstrand ◽  
...  

In the present study, we evaluated the cholesterol-lowering effects of different oat bran (OB) preparations, differing regarding their peak molecular weight (MWp) of β-glucans (2348, 1311, 241, 56, 21 or < 10 kDa), in C57BL/6NCrl mice. The diets were designed to be atherogenic (0·8 % cholesterol and 0·1 % cholic acid), and they reflected the Western diet pattern (41 % energy fat). All OB preparations that were investigated significantly reduced plasma cholesterol when compared with a cellulose-containing control diet, regardless of the molecular weight of β-glucan. Moreover, the difference in viscous properties between the processed OB (from 0·11 to 17·7 l/g) did not appear to play a major role in the cholesterol-lowering properties. In addition, there was no correlation between the molecular weight of β-glucan and the amount of propionic acid formed in caecum. Interestingly, however, there was a significant correlation between the ratio of (propionic acid+butyric acid)/acetic acid and the MWpof β-glucans: the ratio increased with increasing molecular weight. The results of the present study suggest that the molecular weights and viscous properties of β-glucan in oat products may not be crucial parameters for their cholesterol-lowering effects.


Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3200
Author(s):  
Mira J. Pauly ◽  
Julia K. Rohde ◽  
Clara John ◽  
Ioannis Evangelakos ◽  
Anja Christina Koop ◽  
...  

Dietary fibers are fermented by gut bacteria into the major short chain fatty acids (SCFAs) acetate, propionate, and butyrate. Generally, fiber-rich diets are believed to improve metabolic health. However, recent studies suggest that long-term supplementation with fibers causes changes in hepatic bile acid metabolism, hepatocyte damage, and hepatocellular cancer in dysbiotic mice. Alterations in hepatic bile acid metabolism have also been reported after cold-induced activation of brown adipose tissue. Here, we aim to investigate the effects of short-term dietary inulin supplementation on liver cholesterol and bile acid metabolism in control and cold housed specific pathogen free wild type (WT) mice. We found that short-term inulin feeding lowered plasma cholesterol levels and provoked cholestasis and mild liver damage in WT mice. Of note, inulin feeding caused marked perturbations in bile acid metabolism, which were aggravated by cold treatment. Our studies indicate that even relatively short periods of inulin consumption in mice with an intact gut microbiome have detrimental effects on liver metabolism and function.


2021 ◽  
Vol 8 ◽  
Author(s):  
Dien Ye ◽  
Xiaofei Yang ◽  
Liwei Ren ◽  
Hong S. Lu ◽  
Yuan Sun ◽  
...  

Objective: Elevated plasma cholesterol concentrations contributes to ischemic cardiovascular diseases. Recently, we showed that inhibiting hepatic (pro)renin receptor [(P)RR] attenuated diet-induced hypercholesterolemia and hypertriglyceridemia in low-density lipoprotein receptor (LDLR) deficient mice. The purpose of this study was to determine whether inhibiting hepatic (P)RR could attenuate atherosclerosis.Approach and Results: Eight-week-old male LDLR−/− mice were injected with either saline or N-acetylgalactosamine-modified antisense oligonucleotides (G-ASOs) primarily targeting hepatic (P)RR and were fed a western-type diet (WTD) for 16 weeks. (P)RR G-ASOs markedly reduced plasma cholesterol concentrations from 2,211 ± 146 to 1,128 ± 121 mg/dL. Fast protein liquid chromatography (FPLC) analyses revealed that cholesterol in very low-density lipoprotein (VLDL) and intermediate density lipoprotein (IDL)/LDL fraction were potently reduced by (P)RR G-ASOs. Moreover, (P)RR G-ASOs reduced plasma triglyceride concentrations by more than 80%. Strikingly, despite marked reduction in plasma lipid concentrations, atherosclerosis was not reduced but rather increased in these mice. Further testing in ApoE−/− mice confirmed that (P)RR G-ASOs reduced plasma lipid concentrations but not atherosclerosis. Transcriptomic analysis of the aortas revealed that (P)RR G-ASOs induced the expression of the genes involved in immune responses and inflammation. Further investigation revealed that (P)RR G-ASOs also inhibited (P)RR in macrophages and in enhanced inflammatory responses to exogenous stimuli. Moreover, deleting the (P)RR in macrophages resulted in accelerated atherosclerosis in WTD fed ApoE−/− mice.Conclusion: (P)RR G-ASOs reduced the plasma lipids in atherosclerotic mice due to hepatic (P)RR deficiency. However, augmented pro-inflammatory responses in macrophages due to (P)RR downregulation counteracted the beneficial effects of lowered plasma lipid concentrations on atherosclerosis. Our study demonstrated that hepatic (P)RR and macrophage (P)RR played a counteracting role in atherosclerosis.


2019 ◽  
Vol 54 (3) ◽  
pp. 272-280 ◽  
Author(s):  
Rong Wang ◽  
Ruihan Liu ◽  
Lu Li ◽  
Baoning Liu ◽  
Liang Bai ◽  
...  

Plasma lipid and glucose levels are important parameters for evaluating the onset and development of metabolic and cardiovascular diseases. In clinical and experimental studies of humans or mice, fasting is often required before testing plasma lipid and glucose levels. The rabbit is a valuable animal model for cardiovascular disease research. However, whether fasting is necessary for measuring plasma lipid and glucose levels in rabbits remains unclear. In the current study, 12 healthy Japanese white rabbits (males weighing 2.5–3.0 kg) were randomly divided into a chow diet group ( n = 6) and a high cholesterol diet group ( n = 6). They were fed either a standard chow diet or a chow diet supplemented with 0.5% cholesterol and 3% corn oil for 12 weeks. After 12 weeks, the plasma levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and glucose were measured before and after various fasting durations (8, 12, 16, 20 and 24 h). The results showed that there were no significant differences in lipid levels between the fasting and non-fasting samples, whereas glucose levels were lower after 8 h of fasting than in the absence of fasting. Moreover, the glucose levels were restored to normal after 8 h of refeeding. These results indicate that fasting does not affect plasma lipid values in rabbits but that fasting is important for determining the glucose level in rabbits. These findings may be helpful for future rabbit experiments and beneficial for animal welfare.


Author(s):  
Amol Bhalchandra Deore ◽  
Vinayak Dnyandev Sapakal ◽  
Nilofer S. Naikwade

To investigate the antidiabetic, antihyperlipidemic and renal protective activities of the aqueous and ethanol extract of Garcinia indica fruit rinds against alloxan induced diabetes in rats. Wistar rats were made diabetic by a single dose of alloxan hydrate [130 mg/kg i.p.]. After the successful induction of experimental diabetes, rats were divided into five groups each comprising a minimum of six rats. The effects of extracts and glibenclamide on fasting blood glucose, plasma lipid levels and renal profile were examined for 21 days. Blood glucose levels and biochemical parameters such as serum cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, urea and creatinine levels of rats were measured using on weekly intervals i.e day 0, 7, 14 and 21 after daily administration of all extracts at dose of 500 mg/kg. Statistical analysis was performed using Dunnett’s test. p less than 0.01 was taken as the criterion of significance. Oral administration of both aqueous and ethanol extract for 21 days caused a significant [p less than 0.01] reduction in blood glucose levels, lipid profile except HDL; urea and creatinine in diabetic rats. Garcinia indica fruit rind possesses antihyperglycemic activity as well improves total lipid levels and renal profile. It can justify folklore uses of the plant in diabetes.


1973 ◽  
Vol 45 (2) ◽  
pp. 257-262 ◽  
Author(s):  
N. E. Miller ◽  
P. J. Nestel

1. The effects of phenobarbitone on cholesterol and bile acid metabolism have been examined in healthy humans. 2. In three of four subjects the faecal excretion of bile acids was increased by phenobarbitone. This was associated with an increased pool size and turnover of cholic acid. Cholesterol excretion was not clearly affected. The fourth subject who did not respond was also exceptional in not showing an increase in the plasma clearance of antipyrine. 3. The three responsive subjects also developed significant increases in plasma cholesterol and triglyceride concentrations. These findings were associated with an early rise in very-low-density lipoprotein and a fall in plasma cholesterol specific radioactivity in one patient, changes compatible with increased cholesterol synthesis.


1958 ◽  
Vol 195 (1) ◽  
pp. 166-170 ◽  
Author(s):  
B. S. Powers ◽  
N. R. Di Luzio

Adrenalectomized dogs maintained on desoxycorticosterone acetate manifest a progressive depletion of plasma phospholipid and cholesterol. Within a 4-week period a mean decrease of 60% is observed. The daily addition of cholesterol to the Purina chow diet prevented the hypolipemic response and resulted in significant elevation in the concentration of plasma cholesterol. The feeding of an identical amount of cholesterol to dogs with intact adrenals was not associated with any alteration in plasma lipid levels. The feeding of identical amounts of highly saturated fats or soya lecithin to adrenalectomized dogs resulted in the characteristic decline of plasma phospholipid and cholesterol. A significant contribution of the adrenal gland to the regulation of plasma lipid metabolism in normal and cholesterol-fed dogs is indicated.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Xichang Wang ◽  
Kan Chen ◽  
Chenyu Zhang ◽  
Haoyu Wang ◽  
Jiashu Li ◽  
...  

Background. Type 2 deiodinase (Dio2) is a selenoenzyme that is mainly expressed in the endoplasmic reticulum of the central nervous system, brown adipose tissue, and placenta and is responsible for outer ring deiodination of thyroxine (T4) to form biologically active triiodothyronine (T3). The Thr92Ala polymorphism of Dio2 has been found to be a potential risk factor for various diseases beyond the hypothalamus-pituitary-thyroid (HPT) axis. Methods. We searched the relevant studies in the PubMed, Embase, and Cochrane Library databases and Google Scholar. A systematic review and meta-analysis of studies on the Thr92Ala polymorphism and metabolic parameters beyond the HPT axis (e.g., BMI, fasting glycemic traits, plasma lipid levels, and hypertension risk) were performed. Results. Six eligible studies that analyzed the relationship between the Thr92Ala polymorphism and metabolic parameters beyond the thyroid were identified. All selected studies excluded patients with thyroid dysfunction, and diabetic patients were also excluded when fasting glucose and fasting insulin levels were meta-analyzed. The Thr92Ala polymorphism was found to be a significant risk factor for higher BMI (Std. mean difference 0.31 (0.01, 0.60), p = 0.04 ) and higher fasting glucose levels (Std. mean difference 1.18 (0.05, 2.31), p = 0.04 ). However, fasting insulin levels, plasma lipid levels, and hypertension risk showed a nonsignificant association with the Thr92Ala polymorphism. Conclusion. Compared with euthyroid noncarriers (Thr/Thr), euthyroid Ala92-Dio2 carriers showed increased BMI levels, and Ala92-Dio2 carriers also had higher fasting plasma glucose levels than matched euthyroid nondiabetic noncarriers.


2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Elizabeth Tarling ◽  
Joan Cheng ◽  
Angela Cheng ◽  
Pauline Morand ◽  
Bethan Clifford ◽  
...  

Bile acids are detergents and important signaling molecules that activate the nuclear receptor FXR to control key metabolic processes, including feedback mechanisms to maintain bile acid homeostasis. Activation of FXR decreases the mRNA levels of several bile acid synthetic genes, including the rate-limiting enzyme Cyp7a1 . Here we show that Cyp7a1 mRNA levels are very rapidly reduced following FXR activation, indicative of a post-transcriptional mechanism. We identify the RNA binding protein Zfp36l1 as an FXR target gene and show that hepatic overexpression of ZFP36L1 in mice decreases Cyp7a1 mRNA levels. In contrast, Zfp36l1 L -KO mice have increased levels of Cyp7a1 mRNA and biliary bile acids as well as reduced plasma cholesterol levels. Zfp36l1 L -KO mice fed a Western diet have reduced diet-induced obesity and steatosis, likely due to impaired lipid absorption, consistent with increased Cyp7a1 levels. Thus, the ZFP36L1-dependent regulation of bile acid metabolism is an important metabolic contributor of dyslipidemia, obesity and hepatosteatosis.


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