Portal venous bile acids in cholesterol gallstone disease: Effect of treatment with chenodeoxycholic and cholic acids

Quantitative trait locus (QTL) mapping was used to locate genes that determine the difference in cholesterol gallstone disease between the gallstone-susceptible strain C57L/J and the gallstone-resistant strain AKR/J. Gallstone weight was determined in 231 male (AKR × C57L) F1× AKR backcross mice fed a lithogenic diet containing 1% cholesterol, 0.5% cholic acid, and 15% butterfat for 8 wk. Mice having no stones and mice having the largest stones were genotyped at ∼20-cM intervals to find the loci determining cholesterol gallstone formation. The major locus, Lith1, mapped near D2Mit56 and was confirmed by constructing a congenic strain, AK.L- Lith1s. Another locus, Lith2, mapped near D19Mit58 and was also confirmed by constructing a congenic strain AK.L- Lith2s. Other suggestive, but not statistically significant, loci mapped to chromosomes 6, 7, 8, 10, and X. The identification of these Lith genes will elucidate the pathophysiology of cholesterol gallstone formation.

Download Full-text

Effect of ursodeoxycholic acid on lipid metabolism: through the prism of evidence from 2019.

Herald of Pancreatic Club ◽

10.33149/vkp.2020.01.11 ◽

2020 ◽

Vol 46 (1) ◽

pp. 83-88

Author(s):

N. B. Gubergrits ◽

N.V. Byelyayeva ◽

T. L. Mozhyna ◽

G. M. Lukashevich ◽

P. G. Fomenko

Keyword(s):

Lipid Metabolism ◽

Bile Acid ◽

Bile Acids ◽

De Novo ◽

Gallstone Disease ◽

Farnesoid X Receptor ◽

Synthesis Rate ◽

Primary Biliary Cholangitis ◽

Fractional Synthesis Rate ◽

Fractional Synthesis

After the discovery of the method of ursodeoxycholic acid’s (UDCA) synthesis and the publication of evidence confirming its ability to reduce the lithogenic properties of bile, active clinical use of UDCA began in the world. This drug, which has pleiotropic effect (choleretic, cytoprotective, immunomodulatory, antiapoptic, litholytic, hypocholesterolemic), has proven its effectiveness in the treatment various diseases: primary biliary cholangitis, intrahepatic cholestasis of pregnancy, gallstone disease. Being a tertiary bile acid, UDCA stimulates bile acid synthesis by reducing the circulating fibroblast growth factor 19 and inhibiting the activation of the farnesoid X-receptor (FXR), which leads to the induction of cholesterol-7α-hydroxylase, a key enzyme in the synthesis of bile acid de novo, mediating the conversion of cholesterol into bile acids. Changes in the formation of bile acids and cholesterol while taking UDCA intake is accompanied by activation of the main enzyme of cholesterol synthesis - 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Under the influence of UDCA the activity of stearoyl-Coa desaturase (SCD) in visceral white adipose tissue increases. According to studies conducted in 2019, UDCA improves lipid metabolism by regulating the activity of the ACT/mTOR signaling pathway, reduces the synthesis of cholesterol, decreases the fractional synthesis rate of cholesterol and the fractional synthesis rate of triglycerides. It has been proved that UDCA is accompanied by a decrease in the level of total cholesterol and low density lipoprotein cholesterol.

Download Full-text

The Role of Diet in the Pathogenesis of Cholesterol Gallstones

Current Medicinal Chemistry ◽

10.2174/0929867324666170530080636 ◽

2019 ◽

Vol 26 (19) ◽

pp. 3620-3638 ◽

Cited By ~ 7

Author(s):

Agostino Di Ciaula ◽

Gabriella Garruti ◽

Gema Frühbeck ◽

Maria De Angelis ◽

Ornella de Bari ◽

...

Keyword(s):

Vitamin C ◽

Fast Food ◽

Cholesterol Gallstone ◽

Gallstone Disease ◽

Gallstone Formation ◽

Protective Role ◽

Cholesterol Homeostasis ◽

Major Health Problem ◽

Cholesterol Gallstones ◽

Beneficial Effects

: Cholesterol gallstone disease is a major health problem in Westernized countries and depends on a complex interplay between genetic factors, lifestyle and diet, acting on specific pathogenic mechanisms. Overweigh, obesity, dyslipidemia, insulin resistance and altered cholesterol homeostasis have been linked to increased gallstone occurrence, and several studies point to a number of specific nutrients as risk- or protective factors with respect to gallstone formation in humans. There is a rising interest in the identification of common and modifiable dietetic factors that put the patients at risk of gallstones or that are able to prevent gallstone formation and growth. In particular, dietary models characterized by increased energy intake with highly refined sugars and sweet foods, high fructose intake, low fiber contents, high fat, consumption of fast food and low vitamin C intake increase the risk of gallstone formation. On the other hand, high intake of monounsaturated fats and fiber, olive oil and fish (ω-3 fatty acids) consumption, vegetable protein intake, fruit, coffee, moderate alcohol consumption and vitamin C supplementation exert a protective role. : The effect of some confounding factors (e.g., physical activity) cannot be ruled out, but general recommendations about the multiple beneficial effects of diet on cholesterol gallstones must be kept in mind, in particular in groups at high risk of gallstone formation.

Download Full-text