scholarly journals Cholesterol esters selectively delivered in vivo by high-density-lipoprotein subclass LpA-I to rat liver are processed faster into bile acids than are LpA-I/A-II-derived cholesterol esters

1993 ◽  
Vol 292 (3) ◽  
pp. 819-823 ◽  
Author(s):  
M N Pieters ◽  
G R Castro ◽  
D Schouten ◽  
P Duchateau ◽  
J C Fruchart ◽  
...  

High-density lipoprotein (HDL) subclass LpA-I has been reported to promote cholesterol efflux from mouse adipose cells in vitro, whereas subclass LpA-I/A-II has no effect. To investigate whether the apolipoprotein composition of HDL plays a role in the selective delivery of cholesterol esters to the liver in vivo, we labelled HDL in its cholesterol ester moiety and separated [3H]cholesterol oleate-labelled HDL into subclasses LpA-I and LpA-I/A-II by immuno-affinity chromatography. Serum decay and liver association of LpA-I and LpA-I/A-II were compared for the apoprotein and cholesterol ester moieties. Both LpA-I and LpA-I/A-II selectively delivered cholesterol esters to the liver with similar kinetics. The kinetics of biliary secretion of processed cholesterol esters, initially associated with LpA-I or LpA-I/A-II, were studied in rats equipped with permanent catheters in bile, duodenum and heart. For both LpA-I and LpA-I/A-II, liver association was coupled to bile acid synthesis, with an increase in secretion rate during the night. During the first night period, the biliary secretion of LpA-I-derived radio-activity was significantly greater than for LpA-I/A-II. The data indicate that with both LpA-I and LpA-I/A-II selective delivery of cholesterol esters from HDL to the liver occurs, but that cholesterol esters delivered by LpA-I are more efficiently coupled to bile acid synthesis.

1993 ◽  
Vol 21 (4) ◽  
pp. 459S-459S ◽  
Author(s):  
ELENA BRAVO ◽  
ALFREDO CANTAFORA ◽  
TAYFUN GULDUR ◽  
MALCOLM A. MINDHAM ◽  
PETER A. MAYES ◽  
...  

2020 ◽  
Vol 61 (11) ◽  
pp. 1450-1463 ◽  
Author(s):  
Solenne Marion ◽  
Lyne Desharnais ◽  
Nicolas Studer ◽  
Yuan Dong ◽  
Matheus D. Notter ◽  
...  

Bile acids, which are synthesized from cholesterol by the liver, are chemically transformed along the intestinal tract by the gut microbiota, and the products of these transformations signal through host receptors, affecting overall host health. These transformations include bile acid deconjugation, oxidation, and 7α-dehydroxylation. An understanding of the biogeography of bile acid transformations in the gut is critical because deconjugation is a prerequisite for 7α-dehydroxylation and because most gut microorganisms harbor bile acid transformation capacity. Here, we used a coupled metabolomic and metaproteomic approach to probe in vivo activity of the gut microbial community in a gnotobiotic mouse model. Results revealed the involvement of Clostridium scindens in 7α-dehydroxylation, of the genera Muribaculum and Bacteroides in deconjugation, and of six additional organisms in oxidation (the genera Clostridium, Muribaculum, Bacteroides, Bifidobacterium, Acutalibacter, and Akkermansia). Furthermore, the bile acid profile in mice with a more complex microbiota, a dysbiosed microbiota, or no microbiota was considered. For instance, conventional mice harbor a large diversity of bile acids, but treatment with an antibiotic such as clindamycin results in the complete inhibition of 7α-dehydroxylation, underscoring the strong inhibition of organisms that are capable of carrying out this process by this compound. Finally, a comparison of the hepatic bile acid pool size as a function of microbiota revealed that a reduced microbiota affects host signaling but not necessarily bile acid synthesis. In this study, bile acid transformations were mapped to the associated active microorganisms, offering a systematic characterization of the relationship between microbiota and bile acid composition.


1990 ◽  
Vol 268 (3) ◽  
pp. 685-691 ◽  
Author(s):  
H F Bakkeren ◽  
F Kuipers ◽  
R J Vonk ◽  
T J C Van Berkel

Acetylated low-density lipoprotein (acetyl-LDL), biologically labelled in the cholesterol moiety of cholesteryl oleate, was injected into control and oestrogen-treated rats. The serum clearance, the distribution among the various lipoproteins, the hepatic localization and the biliary secretion of the [3H]cholesterol moiety were determined at various times after injection. In order to monitor the intrahepatic metabolism of the cholesterol esters of acetyl-LDL in vivo, the liver was subdivided into parenchymal, endothelial and Kupffer cells by a low-temperature cell-isolation procedure. In both control and oestrogen-treated rats, acetyl-LDL is rapidly cleared from the circulation, mainly by the liver endothelial cells. Subsequently, the cholesterol esters are hydrolysed, and within 1 h after injection, about 60% of the cell- associated cholesterol is released. The [3H]cholesterol is mainly recovered in the high-density lipoprotein (HDL) range of the serum of control rats, while low levels of radioactivity are detected in serum of oestrogen-treated rats. In control rats cholesterol is transported from endothelial cells to parenchymal cells (reverse cholesterol transport), where it is converted into bile acids and secreted into bile. The data thus provide evidence that HDL can serve as acceptors for cholesterol from endothelial cells in vivo, whereby efficient delivery to the parenchymal cells and bile is assured. In oestrogen-treated rats the radioactivity from the endothelial cells is released with similar kinetics as in control rats. However, only a small percentage of radioactivity is found in the HDL fraction and an increased uptake of radioactivity in Kupffer cells is observed. The secretion of radioactivity into bile is greatly delayed in oestrogen-treated rats. It is concluded that, in the absence of extracellular lipoproteins, endothelial cells can still release cholesterol, although for efficient transport to liver parenchymal cells and bile, HDL is indispensable.


2004 ◽  
Vol 24 (2) ◽  
pp. 349-356 ◽  
Author(s):  
Suzanne Lind ◽  
Mats Rudling ◽  
Sverker Ericsson ◽  
Hans Olivecrona ◽  
Mats Eriksson ◽  
...  

1988 ◽  
Vol 82 (1) ◽  
pp. 82-85 ◽  
Author(s):  
W C Duane ◽  
P A Pooler ◽  
J N Hamilton

2007 ◽  
Vol 149 ◽  
pp. S75-S76 ◽  
Author(s):  
Marina Del Puppo ◽  
Federica Corna ◽  
Maria Teresa Dotti ◽  
Emma De Fabiani ◽  
Marzia Galli Kienle

Animals ◽  
2022 ◽  
Vol 12 (2) ◽  
pp. 205
Author(s):  
Di Wu ◽  
Mingjuan Gu ◽  
Zhuying Wei ◽  
Chunling Bai ◽  
Guanghua Su ◽  
...  

Myostatin (MSTN) is a major negative regulator of skeletal muscle mass and causes a variety of metabolic changes. However, the effect of MSTN knockout on bile acid metabolism has rarely been reported. In this study, the physiological and biochemical alterations of serum in MSTN+/− and wild type (WT) cattle were investigated. There were no significant changes in liver and kidney biochemical indexes. However, compared with the WT cattle, lactate dehydrogenase, total bile acid (TBA), cholesterol, and high-density lipoprotein (HDL) in the MSTN+/− cattle were significantly increased, and glucose, low-density lipoprotein (LDL), and triglycerides (TG) were significantly decreased, indicating that MSTN knockout affected glucose and lipid metabolism and total bile acids content. Targeted metabolomic analysis of the bile acids and their derivatives was performed on serum samples and found that bile acids were significantly increased in the MSTN+/− cattle compared with the WT cattle. As the only bile acid synthesis organ in the body, we performed metabolomic analysis on the liver to study the effect of MSTN knockout on hepatic metabolism. Metabolic pathway enrichment analysis of differential metabolites showed significant enrichment of the primary bile acid biosynthesis and bile secretion pathway in the MSTN+/− cattle. Targeted metabolomics data further showed that MSTN knockout significantly increased bile acid content in the liver, which may have resulted from enhanced bile acid synthesis due to the expression of bile acid synthesis genes, cholesterol 7 alpha-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1), and upregulation in the liver of the MSTN+/− cattle. These results indicate that MSTN knockout does not adversely affect bovine fitness but regulates bile acid metabolism via enhanced bile acid synthesis. This further suggests a role of MSTN in regulating metabolism.


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