scholarly journals Compromised Intestinal Lipid Absorption in Mice with a Liver-Specific Deficiency of Liver Receptor Homolog 1

2007 ◽  
Vol 27 (23) ◽  
pp. 8330-8339 ◽  
Author(s):  
Chikage Mataki ◽  
Benjamin C. Magnier ◽  
Sander M. Houten ◽  
Jean-Sébastien Annicotte ◽  
Carmen Argmann ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Dietary Lipids ◽  
The Body ◽  
Water Soluble ◽  
Lipid Absorption ◽  
Whole Body ◽  
Amino Acid Conjugate ◽  
Acid Conjugate ◽  
Mouse Hepatocytes ◽  
Somatic Mutagenesis

ABSTRACT Bile acids (BAs) are water-soluble end products from cholesterol metabolism and are essential for efficient absorption of dietary lipids. By using targeted somatic mutagenesis of the nuclear receptor liver receptor homolog 1 (LRH-1) in mouse hepatocytes, we demonstrate here that LRH-1 critically regulates the physicochemical properties of BAs. The absence of LRH-1 and subsequent deficiency of Cyp8b1 eliminate the production of cholic acid and its amino acid conjugate taurocholic acid and increase the relative amounts of less amphipathic BA species. Intriguingly, while the expression of Cyp8b1 is almost extinguished in the livers of mice that lack LRH-1, the expression of the rate-limiting enzyme of BA synthesis, i.e., Cyp7a1, remains unchanged. The profound remodeling of the BA composition significantly reduces the efficacy of intestinal absorption of lipids and reuptake of BAs and facilitates the removal of lipids from the body. Our studies unequivocally demonstrate a pivotal role for LRH-1 in determining the composition of BAs, which, in turn has major consequences on whole-body lipid homeostasis.

scholarly journals Dietary plant proteins and vegetable oil blends increase adiposity and plasma lipids in Atlantic salmon (Salmo salarL.)

2011 ◽  
Vol 106 (5) ◽  
pp. 633-647 ◽  
Author(s):  
Bente E. Torstensen ◽  
Marit Espe ◽  
Ingunn Stubhaug ◽  
Øyvind Lie
Keyword(s):  
Lipid Metabolism ◽  
Atlantic Salmon ◽  
Fish Oil ◽  
Fish Meal ◽  
Dietary Lipids ◽  
The Body ◽  
Whole Body ◽  
Acid Uptake ◽  
Plant Proteins ◽  
Vldl Assembly

In order to study whether lipid metabolism may be affected by maximum replacement of dietary fish oil and fish meal with vegetable oils (VO) and plant proteins (PP), Atlantic salmon (Salmo salarL.) smolts were fed a control diet containing fish oil and fish meal or one of three plant-based diets through the seawater production phase for 12 months. Diets were formulated to meet all known nutrient requirements. The whole-body lipid storage pattern was measured after 12 months, as well as post-absorptive plasma, VLDL and liver TAG. To further understand the effects on lipid metabolism, expression of genes encoding for proteins involved in VLDL assembly (apoB100), fatty acid uptake (FATP1, cd36, LPL and FABP3, FABP10 and FABP11) were measured in liver and visceral adipose tissue. Maximum dietary VO and PP increased visceral lipid stores, liver TAG, and plasma VLDL and TAG concentrations. Increased plasma TAG correlated with an increased expression of apoB100, indicating increased VLDL assembly in the liver of fish fed the high-plant protein- and VO-based diet. Atlantic salmon fed intermediate replacement levels of VO or PP did not have increased body fat or visceral mass. Overall, the present results demonstrate an interaction between dietary lipids and protein on lipid metabolism, increasing overall adiposity and TAG in the body when fish meal and fish oil are replaced concomitantly at maximised levels of VO and PP.

A minimal model for human whole body cholesterol metabolism

1993 ◽  
Vol 265 (3) ◽  
pp. E513-E520
Author(s):  
R. E. Ostlund
Keyword(s):  
Minimal Model ◽  
Cholesterol Metabolism ◽  
Specific Activity ◽  
Clinical Investigation ◽  
Plasma Cholesterol ◽  
Fractional Excretion ◽  
Compartment Model ◽  
The Body ◽  
Whole Body ◽  
Mean Values

Important work by others has shown that human whole body cholesterol metabolism can be described by a three-compartment model computed from plasma cholesterol specific activity after an intravenous infusion of labeled cholesterol. However, some parameters of that model cannot be estimated precisely [coefficient of variation (CV) 15-19% after 40 wk of follow-up], making its use in routine clinical investigation difficult. On the other hand, a simpler two-compartment model can be calculated with excellent precision from only 10 wk of data (CV 2-8%), but its parameters are inaccurate (for example, the size of the central pool is overestimated by 20%, and the rate constant for fractional excretion of cholesterol from the body is underestimated by 15%). Thus both three-compartment and two-compartment models of cholesterol turnover have important limitations. An alternative is provided by a minimal model that takes advantage of the increased precision expected in the solution of models with fewer parameters. A three-compartment structure is used, but only four (rather than 6 or more) parameters are calculated: the mass of the rapidly mixing central cholesterol compartment, the fractional rate of cholesterol elimination from the body, and the average forward and reverse rate constants for cholesterol transfer between the rapid compartment and both slower compartments. Each of these parameters can be determined unambiguously (without the need to use a minimum or maximum estimate), accurately (mean values within 2% of theory), and with precision (CV 3-13%).(ABSTRACT TRUNCATED AT 250 WORDS)

Pre-digestion of dietary lipids has only minor effects on absorption, retention and metabolism in larval stages of Atlantic cod (Gadus morhua)

2010 ◽  
Vol 105 (6) ◽  
pp. 846-856 ◽  
Author(s):  
K. Hamre ◽  
I. M. Lukram ◽  
I. Rønnestad ◽  
A. Nordgreen ◽  
Ø. Sæle
Keyword(s):  
Gadus Morhua ◽  
Atlantic Cod ◽  
Dietary Lipids ◽  
The Body ◽  
Lipid Absorption ◽  
Lipid Digestion ◽  
Intestinal Tissue ◽  
Larval Stages ◽  
Atlantic Cod Larvae ◽  
Single Meal

The hypothesis of the present study was that cod larvae have a limitation in lipid digestion, and that absorption of lipids would increase by pre-hydrolysation. The diets used were designed to contain 15 % lipid, of which 40 % was phosphatidylcholine (PC) and 60 % was TAG. Cod larvae (40 d post hatch (dph)) were fed a single meal where either PC or TAG was radioactively labelled, and the labelled PC or TAG was either intact or hydrolysed (pre-digested). The larvae were then incubated individually in chambers with collection of CO2 for 10 h. The following fractions were analysed for radioactivity: the incubation water (evacuated feed); the intestine; the body; the CO2 trap. The larvae ate a 16–29 μg diet, equivalent to 3·4–5·2 % of dry body weight. In the whole population, 0–16 % of the lipid was evacuated. The larvae that had eaten less than 1·9–2·7 μg lipid absorbed close to 100 % of the lipid, absorption being defined conservatively as the amount contained in the carcass and CO2, excluding the intestinal tissue. In these larvae, approximately 100 % of the absorbed lipid was also catabolised. In the larvae that ingested more than 1·9–2·7 μg lipid, there was a linear reduction in lipid absorption to a minimum of 55 % at the highest lipid intakes parallel to an increasing retention of lipids in the carcass. There were only minor differences in digestion, absorption, retention and metabolism of lipids between the larvae fed the different diets, and the larvae tended to retain lipid classes as they were present in the feed. The study shows that 40-dph Atlantic cod larvae have an efficient utilisation of dietary lipids supplied as intact PC and TAG.

scholarly journals Mathematical Models for Cholesterol Metabolism and Transport

Processes ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 155
Author(s):  
Fangyuan Zhang ◽  
Brittany Macshane ◽  
Ryan Searcy ◽  
Zuyi Huang
Keyword(s):  
Mathematical Models ◽  
Drug Targets ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
The Body ◽  
Cholesterol Homeostasis ◽  
Whole Body ◽  
Entire Body ◽  
High Cholesterol ◽  
Cholesterol Levels

Cholesterol is an essential component of eukaryotic cellular membranes. It is also an important precursor for making other molecules needed by the body. Cholesterol homeostasis plays an essential role in human health. Having high cholesterol can increase the chances of getting heart disease. As a result of the risks associated with high cholesterol, it is imperative that studies are conducted to determine the best course of action to reduce whole body cholesterol levels. Mathematical models can provide direction on this. By examining existing models, the suitable reactions or processes for drug targeting to lower whole-body cholesterol can be determined. This paper examines existing models in the literature that, in total, cover most of the processes involving cholesterol metabolism and transport, including: the absorption of cholesterol in the intestine; the cholesterol biosynthesis in the liver; the storage and transport of cholesterol between the intestine, the liver, blood vessels, and peripheral cells. The findings presented in these models will be discussed for potential combination to form a comprehensive model of cholesterol within the entire body, which is then taken as an in-silico patient for identifying drug targets, screening drugs, and designing intervention strategies to regulate cholesterol levels in the human body.

Short-term adaptation of postprandial lipoprotein secretion and intestinal gene expression to a high-fat diet

2009 ◽  
Vol 296 (4) ◽  
pp. G782-G792 ◽  
Author(s):  
Sandra Jimena Hernández Vallejo ◽  
Malik Alqub ◽  
Serge Luquet ◽  
Céline Cruciani-Guglielmacci ◽  
Philippe Delerive ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Coordinated Control ◽  
Dietary Lipids ◽  
The Body ◽  
Lipid Absorption ◽  
Hepatic Insulin Resistance ◽  
High Fat ◽  
Short Term

Western diet is characterized by a hypercaloric and hyperlipidic intake, enriched in saturated fats, that is associated with the increased occurrence of metabolic diseases. To cope with this overload of dietary lipids, the intestine, which delivers dietary lipids to the body, has to adapt its capacity in lipid absorption and lipoprotein synthesis. We have studied the early effects of a high-fat diet (HFD) on intestinal lipid metabolism in mice. After 7 days of HFD, mice displayed normal fasting triglyceridemia but postprandial hypertriglyceridemia. HFD induced a decreased number of secreted chylomicrons with increased associated triglycerides. Secretion of larger chylomicrons was correlated with increased intestinal microsomal triglyceride transfer protein (MTP) content and activity. Seven days of HFD induced a repression of genes involved in fatty acid synthesis (FAS, ACC) and an increased expression of genes involved in lipoprotein assembly (apoB, MTP, and apoA-IV), suggesting a coordinated control of intestinal lipid metabolism to manage a high-fat loading. Of note, the mature form of the transcription factor SREBP-1c was increased and translocated to the nucleus, suggesting that it could be involved in the coordinated control of gene transcription. Activation of SREBP-1c was partly independent of LXR. Moreover, HFD induced hepatic insulin resistance whereas intestine remained insulin sensitive. Altogether, these results demonstrate that a short-term HFD is sufficient to impact intestinal lipid metabolism, which might participate in the development of dyslipidemia and metabolic diseases.

scholarly journals Atomically precise silver clusterzymes protect mice from radiation damages

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jiao Guo ◽  
Haiyu Yang ◽  
Ya Liu ◽  
Wei Liu ◽  
Ruiying Zhao ◽  
...  
Keyword(s):  
Cell Viability ◽  
High Efficiency ◽  
Disease Diagnosis ◽  
The Body ◽  
Water Soluble ◽  
Whole Body ◽  
Dna Damages ◽  
Γ Ray

Abstract Background As we know, radiotherapy plays an irreplaceable role in the clinical management on solid tumors. However, due to the non-specific killing effects of ionizing radiation, normal tissues damages would be almost simultaneous inevitably. Therefore, ideal radioprotective agents with high efficiency and low toxicity are always desirable. In this work, atomically precise Ag14 clusterzymes were developed, and their applications in radioprotection were studied in vitro and in vivo for the first time. Methods The ultra-small glutathione supported Ag14 clusterzymes were synthesized by convenient sodium borohydride (NaBH4) reduction of thiolate-Ag (I) complexes and then they were purified by desalting columns. The enzyme-like activity and antioxidant capacity of Ag14 clusterzymes have been tested by various commercial kits, salicylic acid method and electron spin resonance (ESR). Next, they were incubated with L929 cells to evaluate whether they could increase cell viability after γ-ray irradiation. And then Ag14 clusterzymes were intravenously injected into C57 mice before 7 Gy whole-body γ-ray irradiation to evaluate the radioprotection effects in vivo. At last, the in vivo toxicities of Ag14 clusterzymes were evaluated through biodistribution test, hematological details, serum biochemical indexes and histological test in female Balb/c mice with intravenous injection of Ag14 clusterzymes. Results Our studies suggested atomically precise Ag14 clusterzymes were potential radioprotectants. Ag14 clusterzymes exhibited unique superoxide dismutase (SOD)-like activity, strong anti-oxidative abilities, especially on •OH scavenging. The Ag14 clusterzymes could effectively improve cell viability through eliminating ROS and prevent DNA damages in cells dealt with γ-ray irradiation. In vivo experiments showed that Ag14 clusterzymes could improve the irradiated mice survival rate by protecting hematological systems and repairing tissue oxidative stress damage generated by γ-ray irradiation. In addition, bio-distribution and toxicological experiments demonstrated that the ultrasmall Ag14 clusterzymes could be excreted quickly from the body by renal clearance and negligible toxicological responses were observed in mice up to 30 days. Conclusion In summary, atomically precise, ultrasmall and water soluble Ag14 clusterzymes with SOD-like activity were successfully developed and proved to be effective both in vitro and in vivo for radioprotection. Furthermore, with atomically precise molecular structure, Ag14 clusterzymes, on aspect of the catalytic and optical properties, may be improved by structure optimization on atom-scale level for other applications in disease diagnosis and treatment. Graphical Abstract

A cholesterol-free, high-fat diet suppresses gene expression of cholesterol transporters in murine small intestine

2008 ◽  
Vol 294 (5) ◽  
pp. G1171-G1180 ◽  
Author(s):  
Heleen M. de Vogel-van den Bosch ◽  
Nicole J. W. de Wit ◽  
Guido J. E. J. Hooiveld ◽  
Hanneke Vermeulen ◽  
Jelske N. van der Veen ◽  
...  
Keyword(s):  
Small Intestine ◽  
High Fat Diet ◽  
Unsaturated Fatty Acids ◽  
Cholesterol Metabolism ◽  
The Body ◽  
Whole Body ◽  
Intestinal Lumen ◽  
High Fat ◽  
Biliary Cholesterol ◽  
Cholesterol Transporters

Transporters present in the epithelium of the small intestine determine the efficiency by which dietary and biliary cholesterol are taken up into the body and thus control whole-body cholesterol balance. Niemann-Pick C1 Like Protein 1 (Npc1l1) transports cholesterol into the enterocyte, whereas ATP-binding cassette transporters Abca1 and Abcg5/Abcg8 are presumed to be involved in cholesterol efflux from the enterocyte toward plasma HDL and back into the intestinal lumen, respectively. Abca1, Abcg5, and Abcg8 are well-established liver X receptor (LXR) target genes. We examined the effects of a high-fat diet on expression and function of cholesterol transporters in the small intestine in mice. Npc1l1, Abca1, Abcg5, and Abcg8 were all downregulated after 2, 4, and 8 wk on a cholesterol-free, high-fat diet. The high-fat diet did not affect biliary cholesterol secretion but diminished fractional cholesterol absorption from 61 to 42% ( P < 0.05). In an acute experiment in which triacylglycerols of unsaturated fatty acids were given by gavage, we found that this downregulation occurs within a 6-h time frame. Studies in LXRα-null mice, confirmed by in vitro data, showed that fatty acid-induced downregulation of cholesterol transporters is LXRα independent and associated with a posttranslational increase in 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity that reflects induction of cholesterol biosynthesis as well as with a doubling of neutral fecal sterol loss. This study highlights the induction of adaptive changes in small intestinal cholesterol metabolism during exposure to dietary fat.

A Simple and Inexpensive Clinical Whole Body Counter

1976 ◽  
Vol 15 (05) ◽  
pp. 248-253
Author(s):  
A. K. Basu ◽  
S. K. Guha ◽  
B. N. Tandon ◽  
M. M. Gupta ◽  
M. ML. Rehani
Keyword(s):  
The Body ◽  
Whole Body ◽  
Vitro Assay ◽  
Body Counter ◽  
Optimum Parameters ◽  
Whole Body Counter ◽  
Single Detector ◽  
Background Index ◽  
Iodide Crystal

SummaryThe conventional radioisotope scanner has been used as a whole body counter. The background index of the system is 10.9 counts per minute per ml of sodium iodide crystal. The sensitivity and derived sensitivity parameters have been evaluated and found to be suitable for clinical studies. The optimum parameters for a single detector at two positions above the lying subject have been obtained. It has been found that for the case of 131I measurement it is possible to assay a source located at any point in the body with coefficient of variation less than 5%. To add to the versatility, a fixed geometry for in-vitro counting of large samples has been obtained. The retention values obtained by the whole body counter have been found to correlate with those obtained by in-vitro assay of urine and stool after intravenous administration of 51Cr-albumin.

Visualization of Invasion into the Body and Internal Diffusion of Nanoparticles

2008 ◽  
Vol 396-398 ◽  
pp. 569-572
Author(s):  
Fumio Watari ◽  
Shigeaki Abe ◽  
I.D. Rosca ◽  
Atsuro Yokoyama ◽  
Motohiro Uo ◽  
...  
Keyword(s):  
Biomedical Applications ◽  
Fluorescent Microscopy ◽  
The Body ◽  
Internal Diffusion ◽  
Whole Body ◽  
X Ray ◽  
Body Level ◽  
Organ Level ◽  
Level 2 ◽  
Internal Body

Nanoparticles may invade directly into the internal body through the respiratory or digestive system and diffuse inside body. The behavior of nanoparticles in the internal body is also essential to comprehend for the realization of DDS. Thus it is necessary to reveal the internal dynamics for the proper treatments and biomedical applications of nanoparticles. In the present study the plural methods with different principles such as X-ray scanning analytical microscope (XSAM), MRI and Fluorescent microscopy were applied to enable the observation of the internal diffusion of micro/nanoparticles in the (1) whole body level, (2) inner organ level and (3) tissue and intracellular level. Chemical analysis was also done by ICP-AES for organs and compared with the results of XSAM mapping.

scholarly journals Detection of Acetaminophen and Its Glucuronide in Fingerprint by SALDI Mass Spectrometry Using Zeolite and Study of Time-Dependent Changes in Detected Ion Amount

Analytica ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 66-75
Author(s):  
Toshiki Horikoshi ◽  
Chihiro Kitaoka ◽  
Yosuke Fujii ◽  
Takashi Asano ◽  
Jiawei Xu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Glucuronic Acid ◽  
Laser Desorption ◽  
The Body ◽  
Time Dependent ◽  
Laser Desorption Ionization ◽  
Fingerprint Analysis ◽  
Desorption Ionization ◽  
Acid Conjugate ◽  
Over Time

The ingredients of an antipyretic (acetaminophen, AAP) and their metabolites excreted into fingerprint were detected by surface-assisted laser desorption ionization (SALDI) mass spectrometry using zeolite. In the fingerprint taken 4 h after AAP ingestion, not only AAP but also the glucuronic acid conjugate of AAP (GAAP), caffeine (Caf), ethenzamide (Eth), salicylamide (Sala; a metabolite of Eth), and urea were detected. Fingerprints were collected over time to determine how the amounts of AAP and its metabolite changed with time, and the time dependence of the peak intensities of protonated AAP and GAAP was measured. It was found that the increase of [GAAP+H]+ peak started later than that of [AAP+H]+ peak, reflecting the metabolism of AAP. Both AAP and GAAP reached maximum concentrations approximately 3 h after ingestion, and were excreted from the body with a half-life of approximately 3.3 h. In addition, fingerprint preservation was confirmed by optical microscopy, and fingerprint shape was retained even after laser irradiation of the fingerprint. Our method may be used in fingerprint analysis.

Sign in / Sign up

Export Citation Format

Share Document