ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P154 | DOI: 10.1530/endoabs.63.P154

The role of bile acids in the pathogenesis of NAFLD

Zvenigorodskaya Larusa, Nilova Tamara, Petrakov Alexander, Varvanina Galina & Shinkin Mikhail

Moscow Clinical Scientific Center named after A.S. Loginov, Moscow, Russian Federation.

Obesity affects on the composition of bile: the lithogenicity of bile increases, biliary sludge and cholelithiasis are developing. Under the influence of the active form of oxygen, abnormal forms of bile acids are formed, which negatively affects the development and progression of the pathological process. With the development of inflammation in the liver and pancreas, disturbances in the membrane proteins of glucose transporters occur, the activity of nuclear receptors for the synthesis and conjugation of bile acids decreases. Ursodeoxycholic acid activates nuclear receptors, improves sensitivity to insulin, leptin, ghrelin, adiponectin, increases the activity of glucose transporters, lipoproteinlipase and other enzymes.

Objective: To determine the effect of inflammation markers (NO, LPS, FLA2, MDA) on the synthesis and transport of bile acids in patients with NAFLD and diabetes.

Materials and methods: 158 patients with NAFLD: 46 patients with DM2 and 112 patients with IGT were examined. Activation of LPO stimulates fibrogenesis and progression of the pathological process in the liver. The level of LPO was determined by the content of MDA. NO metabolites- by screening FLA2, LPS- by chromogenic end point method using LAL test. Pharmacotherapy with Ursosan in 50 patients with NAFLD.

Results: Group I included 59 patients with NAFLD and DM in which the content of bile acids was lower by 45% compared with the control group was 2.97±1.02 μmol\l the control group consisted of practically healthy persons without disorders of carbohydrate metabolism of 56 patients with the LCD level of 5.4±1.8 mmol\l. group II: NAFLD patients with IGT, n=21;LCD 8.88±4.94 mmol/l, P=0.0001. MDA in group I (24.12±1.64 μmol\l) was increased compared to the control (9.94±1.62 μmol\l). NO metabolites in group I was increased (137.7±35.96 μmol\l). The activity of FLA2 at CD2 median 605 (504–826) ng\ml and LPS=3.69 EE\ml, at NTG median 430 (324–497) ng\ml (P=0.001), LPS=1.43 EE\ml. A negative correlation r=–578 (FLA2/MDA). After 12 weeks treatment with Ursosan, inflammation markers decreased, biochemical parameters improved.

Conclusions: In patients with NAFLD with DM there is a decrease in the synthesis of bile acids and a violation of bile acid transport, which is associated with damage to cell membranes, inhibition of enzyme systems and inflammation. Accumulation of products of lipid peroxidation leads to the damage of hepatocyte membranes, impaired synthesis of bile acids in the liver, it inhibits the transporters of bile acids. Replacement therapy with Ursosan is recommended in NAFLD.

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