Mechanism for elevation of hepatic cholesterol synthesis and serum cholesterol levels in triton WR-1339-induced hyperlipidemia

Author(s):  
Masao Kuroda ◽  
Kazuhiko Tanzawa ◽  
Yoshio Tsujita ◽  
Akira Endo
Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1848 ◽  
Author(s):  
Elizabeth Babawale ◽  
Peter Jones ◽  
Kelly Mercer ◽  
Haixia Lin ◽  
Laxmi Yeruva ◽  
...  

Formula-fed infants present higher cholesterol synthesis rates and lower circulating cholesterol during the postnatal feeding period compared to breast-fed infants, though the mechanisms underlying this phenotype are not fully understood. Typical infant formulas contain vegetable-based fats, inherently including phytosterols (PS), which are structurally similar to cholesterol and may interfere with their absorption. A seven-day old piglets model was used to test the inhibitory effects of PS on cholesterol absorption during postnatal feeding. Following feeding for 21 days with milk-based formulas containing PS and cholesterol levels resembling those in formulas or human-milk, apparent cholesterol digestibility was analyzed in ileal digesta, and cholesterol, PS, and cholesterol synthesis markers were analyzed in plasma and liver samples. Ileal cholesterol digestibility content was increased in the piglets fed low PS formulas and the rate of the hepatic cholesterol synthesis, as determined by the lathosterol-to-cholesterol ratios (L:C), was decreased in the piglets fed LP-formulas and corresponded to reduced nuclear expression of SREBP2 relative to those fed HP-formulas. These results are consistent with the hypothesis that PS in formula can inhibit cholesterol absorption and enhance cholesterol synthesis. Whether or not this leads to entrainment of cholesterol synthesis later in life via early programming awaits further research.


BMC Biology ◽  
2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Tiphaine Le Roy ◽  
Emelyne Lécuyer ◽  
Benoit Chassaing ◽  
Moez Rhimi ◽  
Marie Lhomme ◽  
...  

Abstract Background Management of blood cholesterol is a major focus of efforts to prevent cardiovascular diseases. The objective of this study was to investigate how the gut microbiota affects host cholesterol homeostasis at the organism scale. Results We depleted the intestinal microbiota of hypercholesterolemic female Apoe−/− mice using broad-spectrum antibiotics. Measurement of plasma cholesterol levels as well as cholesterol synthesis and fluxes by complementary approaches showed that the intestinal microbiota strongly regulates plasma cholesterol level, hepatic cholesterol synthesis, and enterohepatic circulation. Moreover, transplant of the microbiota from humans harboring elevated plasma cholesterol levels to recipient mice induced a phenotype of high plasma cholesterol levels in association with a low hepatic cholesterol synthesis and high intestinal absorption pattern. Recipient mice phenotypes correlated with several specific bacterial phylotypes affiliated to Betaproteobacteria, Alistipes, Bacteroides, and Barnesiella taxa. Conclusions These results indicate that the intestinal microbiota determines the circulating cholesterol level and may thus represent a novel therapeutic target in the management of dyslipidemia and cardiovascular diseases.


1955 ◽  
Vol 101 (3) ◽  
pp. 225-232 ◽  
Author(s):  
Ivan D. Frantz ◽  
Beverly T. Hinkelman

Synthesis of cholesterol from acetate in the rat was studied after injection of triton WR-1339, both in the whole animal and by the liver slice technique. Synthesis appeared to be increased 3-fold 24 hours after the injection. It was depressed after 72 hours, concurrently with a rise in the cholesterol concentration in the liver and its fall towards normal in the blood. When triton was injected into cholesterol-fed animals, or when their bile ducts were ligated, cholesterol synthesis was faster than in the untreated, normally fed controls, despite, in some instances, an elevated concentration of cholesterol in the liver.


1979 ◽  
Vol 34 (4) ◽  
pp. 383-389 ◽  
Author(s):  
Philip D. Schneider ◽  
Ignacio J. Guzman ◽  
Richard D. Rucker ◽  
Thomas G. Stocks ◽  
Richard L. Varco ◽  
...  

1994 ◽  
Vol 109 (1-2) ◽  
pp. 252 ◽  
Author(s):  
G.J. Smith ◽  
R.G. Davidson ◽  
C. Dunkley ◽  
G.R. Brown ◽  
K.B. Mallion ◽  
...  

Nutrition ◽  
2020 ◽  
Vol 79-80 ◽  
pp. 110954
Author(s):  
Reyhan Nergiz-Unal ◽  
Elif Ulug ◽  
Betul Kisioglu ◽  
Funda Tamer ◽  
Mahmut Bodur ◽  
...  

1999 ◽  
Vol 276 (5) ◽  
pp. G1165-G1173 ◽  
Author(s):  
Jeffrey W. Chisholm ◽  
Patrick Nation ◽  
Peter J. Dolphin ◽  
Luis B. Agellon

In α-naphthylisothiocyanate-treated mice, plasma phospholipid (PL) levels were elevated 10- and 13-fold at 48 and 168 h, respectively, whereas free cholesterol (FC) levels increased between 48 h (17-fold) and 168 h (39-fold). Nearly all of these lipids were localized to lipoprotein X-like particles in the low-density lipoprotein density range. The PL fatty acyl composition was indicative of biliary origin. Liver cholesterol and PL content were near normal at all time points. Hepatic hydroxymethylglutaryl CoA reductase activity was increased sixfold at 48 h, and cholesterol 7α-hydroxylase activity was decreased by ∼70% between 24 and 72 h. These findings suggest a metabolic basis for the appearance of abnormal plasma lipoproteins during cholestasis. Initially, PL and bile acids appear in plasma where they serve to promote the efflux of cholesterol from hepatic cell membranes. Hepatic cholesterol synthesis is then likely stimulated in the response to the depletion of hepatic cell membranes of cholesterol. We speculate that the enhanced synthesis of cholesterol and impaired conversion to bile acids, particularly during the early phase of drug response, contribute to the accumulation of FC in the plasma.


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