Comparative effects of cholic, chenodeoxycholic, and ursodeoxycholic acids on micellar solubilization and intestinal absorption of cholesterol

Reynier, M.O.; Montet, Jean-Claude; Gérolami, A; Marteau, C.; Crotté, C.; Montet, Anne-Marie; Mathieu, Sophie

doi:10.1016/s0022-2275(20)34961-0

Cited by 105 publications

(15 citation statements)

References 26 publications

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“…This important physico-chemical parameter reflects the propensity to form miscellar aggregates and to facilitate the transport of liposoluble molecules, such as cholesterol; it is a relevant parameter for evaluation of the biological activity of a BA. With a low CMC, CA is much more efficient than CDCA in facilitating the absorption of dietary cholesterol from WD (26,27).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Cyp7a1 by Cholic Acid and Chenodeoxycholic Acid in Cyp27a1/ApoE Double Knockout Mice: Differential Cardiovascular Outcome

et al. 2020

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Sterol 27-hydroxylase (CYP27A1) is a key enzyme in bile acids (BAs) biosynthesis and a regulator of cholesterol metabolism. Cyp27a1/Apolipoprotein E double knockout (DKO) mice fed with western diet (WD) are protected from atherosclerosis via up-regulation of hepatic Cyp7a1 and Cyp3a11. Since feeding BAs ameliorates metabolic changes in Cyp27a1 KO mice, we tested BAs feeding on the development of atherosclerosis in DKO mice. DKO mice were fed for 8 weeks with WD containing 0.1% cholic acid (CA) (WD-CA) or chenodeoxycholic acid (CDCA) (WD-CDCA). Atherosclerotic lesions, plasma lipoprotein composition and functionality, hepatic lipid content, BAs amount and composition, expression of genes involved in lipid metabolism and BA signaling in liver and intestine as well as intestinal cholesterol absorption were assessed. Hepatic Cyp7a1 and Cyp3a11 expression were reduced by 60% after feeding with both WD-CA and WD-CDCA. After feeding with WD-CA we observed a 40-fold increase in the abundance of atherosclerotic lesions in the aortic valve, doubling of the levels of plasma total and low density lipoprotein cholesterol and halving of the level of high density lipoprotein cholesterol. Furthermore, in these mice plasma cholesterol efflux capacity decreased by 30%, hepatic BA content increased 10-fold, intestinal cholesterol absorption increased 6fold. No such changes were observed in mice fed with WD-CDCA. Despite similar reduction on Cyp7a1 and Cyp3a11 hepatic expression, CA and CDCA have a drastically different impact on development of atherosclerosis, plasma and hepatic lipids, BAs composition and intestinal absorption. Reduced cholesterol absorption contributes largely to athero-protection in DKO mice.

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Section: Discussionmentioning

confidence: 99%

Downregulation of Cyp7a1 by Cholic Acid and Chenodeoxycholic Acid in Cyp27a1/ApoE Double Knockout Mice: Differential Cardiovascular Outcome

et al. 2020

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“…Bile acids can also be synthesized via the 7 ␣ -hydroxylation of several different oxysterols; this pathway is referred to as the "acidic" or "alternative" bile acid synthetic pathway (6). There are at least two different enzymes that 7 ␣hydroxylate oxysterols: CYP7B1, which 7 ␣ -hydroxylates several different oxysterols (e.g., 25-hydroxycholesterol, 27-hydroxycholesterol) (7,8) and CYP39A1, which appears to react only with 24-hydroxycholesterol (9). The production of 24-hydroxycholesterol by CYP46 accounts for the major metabolic pathway for cholesterol in the brain (10).…”

Section: There Are Two Distinct Bile Acid Biosynthetic Pathwaysmentioning

confidence: 99%

“…This rigid amphipathic planar structure facilitates the ability of bile acids to act as effective detergents necessary for the digestion and intestinal absorption of hydrophobic nutrients (e.g., lipids and fat soluble vitamins). Perhaps the most compelling evidence demonstrating the functional importance of the "amphipathic sidedness" of the steroidal planar structure of bile acids is that biotransformation of chenodeoxycholic acid into ursodeoxycholic acid via changing the 7 ␣ -hydroxy group to a 7 ␤ -hydroxy group markedly decreases its amphipathic/detergent properties (25,26).…”

Section: Bile Acids Are Effective Detergentsmentioning

confidence: 99%

Regulation of cholesterol-7α-hydroxylase: BAREly missing a SHP

Davis

Miyake

Hui

et al. 2002

Journal of Lipid Research

155

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Cholesterol-7 ␣ -hydroxylase (CYP7A1) regulates the pathway through which cholesterol is converted into bile acids. The unique detergent properties of bile acids are essential for the digestion and intestinal absorption of hydrophobic nutrients. Bile acids have potent toxic properties (e.g., membrane disruption) and there are a plethora of mechanisms to limit their accumulation in blood and tissues. The discovery of farnesoid X receptor (FXR), the nuclear receptor activated specifically by bile acids, has opened new insights into these mechanisms. Bile acid activation of FXR has been shown to repress the expression of CYP7A1 via increasing the expression of small heterodimer partner (SHP), a non-DNA binding protein. The increased abundance of SHP causes it to associate with liver receptor homolog (LRH)-1, an obligate factor required for transcription of CYP7A1. Recent studies show there is an "FXR/ SHP-independent" mechanism that also represses CYP7A1 expression. This "FXR/SHP-independent" pathway involves the interaction of bile acids with liver macrophages (i.e., Kupffer cells), which induces the expression, and secretion of cytokines. These inflammatory cytokines, which include tumor necrosis factor ␣ and interleukin-1 ␤ , act upon liver parenchymal cells causing a rapid repression of the CYP7A1 gene. -

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“…Any factor that changes the transportation of Ch from the intestinal lumen to the lymph may influence intestinal Ch absorption efficiency. Table 1 summarizes dietary factors (7)(8)(9)(10)(11)(12)(13)(14)(15)(16), including administered therapeutic agents, biliary factors (17)(18)(19)(20)(21), cellular factors , and lumenal factors (43)(44)(45) that could influence intestinal Ch absorption. Despite these findings, it remains poorly understood which step(s) in the absorption process differ inherently among individuals in any population to explain variations in intestinal Ch absorption efficiency.…”

mentioning

confidence: 99%

Genetic factors at the enterocyte level account for variations inintestinal cholesterol absorption efficiency among inbred strains of mice

Wang

Paigen

Carey

2001

Journal of Lipid Research

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Interindividual and interstrain variations in cholesterol absorption efficiency occur in humans and animals. We investigated physiological biliary and small intestinal factors that might determine variations in cholesterol absorption efficiency among inbred mouse strains. We found that there were significant differences in cholesterol absorption efficiency measured by plasma, fecal, and lymphatic methods: Ͻ 25% in AKR/J, C3H/J, and A/J strains; 25-30% in SJL/J, DBA/2J, BALB/cJ, SWR/J, and SM/J strains; and 31-40% in C57L/J, C57BL/6J, FVB/J, and 129/SvJ strains. In (AKR ϫ C57L)F 1 mice, the cholesterol absorption efficiency (31 ؎ 6%) mimicked that of the C57L parent (37 ؎ 5%) and was significantly higher than in AKR mice (24 ؎ 4%). Although biliary bile salt compositions and small intestinal transit times were similar, C57L mice displayed significantly greater bile salt secretion rates and pool sizes than AKR mice. In examining lymphatic cholesterol transport in the setting of a chronic biliary fistula, C57L mice displayed significantly higher cholesterol absorption rates compared with AKR mice. Because biliary and intestinal transit factors were accounted for, we conclude that genetic variations at the enterocyte level determine differences in murine cholesterol absorption efficiency, with high cholesterol absorption likely to be a dominant trait. This study provides baseline information for identifying candidate genes that regulate intestinal cholesterol absorption at the cellular level. -Wang, D. Q-H., B. Paigen, and M. C. Carey. Genetic factors at the enterocyte level account for variations in intestinal cholesterol absorption efficiency among inbred strains of mice.

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Comparative effects of cholic, chenodeoxycholic, and ursodeoxycholic acids on micellar solubilization and intestinal absorption of cholesterol

Cited by 105 publications

References 26 publications

Downregulation of Cyp7a1 by Cholic Acid and Chenodeoxycholic Acid in Cyp27a1/ApoE Double Knockout Mice: Differential Cardiovascular Outcome

Downregulation of Cyp7a1 by Cholic Acid and Chenodeoxycholic Acid in Cyp27a1/ApoE Double Knockout Mice: Differential Cardiovascular Outcome

Regulation of cholesterol-7α-hydroxylase: BAREly missing a SHP

Genetic factors at the enterocyte level account for variations inintestinal cholesterol absorption efficiency among inbred strains of mice

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