P429 URSODEOXYCHOLIC ACID VIA REGULATION OF BILE ACIDS AND MAMMALIAN TARGET OF RAPAMYCIN TO IMPROVE LIPID METABOLISM DISORDERS WITH NON-ALCOHOLIC AND ALCOHOL-INDUCED FATTY LIVER DISEASE

2014 ◽  
Vol 60 (1) ◽  
pp. S211
Author(s):  
H.M. Liu ◽  
T.Y. Lee ◽  
J.F. Liao ◽  
H.C. Lin
Doctor Ru ◽  
2020 ◽  
Vol 19 (7) ◽  
pp. 21-30
Author(s):  
N.B. Gubergritz ◽  
◽  
N.V. Belyaeva ◽  
T.L. Mozhina ◽  
N.E. Monogarova ◽  
...  

Objective of the Review: to analyse changes in bile acids (BA) metabolism due to nonalcoholic fatty liver disease (NAFL), nonalcoholic fatty pancreas disease (NAFP); to assess the efficiency of ursodeoxycholic acid (UDCA) for their correction. Key Points. NAFL and NAFP have much in common, including BA synthesis imbalance and reduced farnesoid X receptor (FXR) expression. One possible therapy of NAFL and NAFP is BA synthesis correction and increase in FXR expression using FXR agonists. The article discusses clinical and experimental trials of the efficiency of selective FXR agonist — UDCA — in NAFL and NAFP. Conclusion. The multifactorial UDCA mechanism of action including anti-inflammatory, antioxidant, cytoprotective and antiapoptotic actions, can normalise carbohydrate, lipid metabolism and activate FXR; it can justify medicine inclusion into NAFL and NAFP therapeutic regimens. Keywords: nonalcoholic fatty liver disease, nonalcoholic fatty pancreas disease, ursodeoxycholic acid.


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2978
Author(s):  
Stanislav Kotlyarov ◽  
Aleksei Bulgakov

Non-alcoholic fatty liver disease (NAFLD) is currently among the most common liver diseases. Unfavorable data on the epidemiology of metabolic syndrome and obesity have increased the attention of clinicians and researchers to the problem of NAFLD. The research results allow us to emphasize the systemicity and multifactoriality of the pathogenesis of liver parenchyma lesion. At the same time, many aspects of its classification, etiology, and pathogenesis remain controversial. Local and systemic metabolic disorders are also a part of the pathogenesis of chronic obstructive pulmonary disease and can influence its course. The present article analyzes the metabolic pathways mediating the links of impaired lipid metabolism in NAFLD and chronic obstructive pulmonary disease (COPD). Free fatty acids, cholesterol, and ceramides are involved in key metabolic and inflammatory pathways underlying the pathogenesis of both diseases. Moreover, inflammation and lipid metabolism demonstrate close links in the comorbid course of NAFLD and COPD.


Author(s):  
M. M. Dolzhenko ◽  
L. I. Konoplyanik

The clinical morphological manifestations of the course of non‑alcoholic fatty liver disease in patients, non‑alcohol drinkers, include steatohepatosis, non‑alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. There are four basic mechanisms in the pathogenesis of non‑alcoholic fatty liver disease: bile acid lipotoxicity, insulin resistance, systemic inflammation, increased oxidative stress and lipid peroxidation. Non‑alcoholic fatty liver disease increases the risk of onset, development and progression of the cardiovascular diseases independently from other predictors and manifestations of the metabolic syndrome. The complex treatment of patients with coronary heart disease, combined with the non‑alcoholic fatty liver disease includes diet, physical exercises, body mass reduction and drug therapy. The medications for this category of patients must be maximal safe and result in the improving of the clinical, laboratory and morphological parameters of liver. Ursodeoxycholic acid is one of the most effective medications with the mechanisms of action associated with the normalization of the hepatoenteric circulation of bile acids and a number of biologically active substances. It also possesses the cytoprotective and antiapoptotic action, affects the FXR­metabolic nuclear receptor, which plays an important role in the physiology of vascular pathology, is an important transcriptional regulator of bile acids, lipids and glucose metabolism. Ursodeoxycholic acid is able to suppress eosinophilic inflammation not only in the gastrointestinal tract. It improves histopathological changes in airway remodeling, that can be connected with the modulation of cytokines and inhibition of apoptosis of epithelial cells of the respiratory tract. Ursodeoxycholic acid can be potentially effective preparation for the reduction of fluid volume in pulmonary edema and prevention of lung damage caused by fat embolism syndrome. Moreover, its positive effects have been proved as regards the airway epithelial cells at cystic fibrosis. Taking into account that ursodeoxycholic acid inhibits pro‑inflammatory cytokines, has strong antioxidative properties and acts as a famous hepatoprotector, it can be effective in the treatment of coronavirus disease (COVID­19). In Ukraine Ursonost is available, it is one of the well‑known preparations containing ursodeoxycholic acid and advantageously distinguished by high quality and ease of dosing. It is bioequivalent to the reference drug due to the highest quality of the substance and modern production technology. The large evidence base on ursodeoxycholic acid allows the drug Ursonost to be considered as a drug with pronounced multipotent properties, thus it is indicated for the treatment of patients with non‑alcoholic and alcoholic fatty liver disease, especially in combination with the coronary heart disease, of conditions, associated with bile reflux (duodenogastric, duodenogastroesophageal reflux), biliary sludge, primary biliary cirrhosis, gallstone disease (for dissolving X‑ray negative stones) and other metabolic disorders. Ursonost preparation is available as 150 and 300 mg capsules, that facilitates the drug dosing depending on the body mass of a patient and a clinical situation.


2017 ◽  
Vol 35 (3) ◽  
pp. 282-287 ◽  
Author(s):  
Daniel Steinacher ◽  
Thierry Claudel ◽  
Michael Trauner

Non-alcoholic fatty liver disease is one of the most rapidly rising clinical problems in the 21st century. So far no effective drug treatment has been established to cure this disease. Bile acids (BAs) have a variety of signaling properties, which can be used therapeutically for modulating hepatic metabolism and inflammation. A side-chain shorted derivative of ursodeoxycholic acid (UDCA) is 24 nor-ursodeoxycholic acid (NorUDCA) and it represents a new class of drugs for treatment of liver diseases. NorUDCA has unique biochemical and therapeutic properties, since it is relatively resistant to conjugation with glycine or taurine compared to UDCA. NorUDCA undergoes cholehepatic shunting, resulting in ductular targeting, bicarbonate-rich hypercholeresis, and cholangiocyte protection. Furthermore, it showed anti-fibrotic, anti-inflammatory, and anti-lipotoxic properties in several animal models. As such, NorUDCA is a promising new approach in the treatment of cholestatic and metabolic liver diseases. This review is a summary of current BA-based therapeutic approaches in the treatment of the fatty liver disease.


2019 ◽  
Vol 1 (6) ◽  
pp. 47-52
Author(s):  
A. B. Krivosheev ◽  
A. D. Kuimov ◽  
T. A. Tuguleva

The aim of the study was to determine for patients with non-alcoholic fatty liver disease (NAFLD) the possibilities and effectiveness of the course use of chloride-bicarbonate sodium mineral water (MW) (by the example of MW Karachinskaya). A total of 76 patients (20 women and 56 men) with NAFLD aged 42 to 72 years (mean age 59.4 ± 1.2 years) were examined. MV was taken in 200 ml in 8, 10, 12, 15 and 17 hours (5 times a day, in a volume of 1,000 ml), room temperature (18-20 °C). The course of treatment was 10 days. In the dynamics of treatment, lipid spectrum parameters were evaluated: total cholesterol, triglycerides, high, low and very low density lipoprotein cholesterol, atherogenic index. The results obtained allow us to draw the following conclusions. 1. In patients with NAFLD observed by us, comorbid pathology is observed at least 3-4 diseases of internal organs are registered at the same time. The most frequently detected pathology of the cardiovascular system and disorders of carbohydrate metabolism. 2. The vast majority of patients revealed lipid metabolism disorders. The most significant disorders were characterized by increased levels of total cholesterol. 3. The inclusion of the 10-day drinking course of the chloride-bicarbonate sodium MW Karachinskaya’ contributes to the correction of lipid metabolism. The identified cholesterol-lowering effect of MW Karachinskaya' with mild and moderate hypercholesterolemia allows recommending it for non-pharmacological correction of elevated total cholesterol, which is currently considered as an established risk factor for IHD and arterial hypertension.


2021 ◽  
Vol 15 (1) ◽  
pp. 21-35
Author(s):  
Yana Geng ◽  
Klaas Nico Faber ◽  
Vincent E. de Meijer ◽  
Hans Blokzijl ◽  
Han Moshage

Abstract Background Non-alcoholic fatty liver disease (NAFLD), characterized as excess lipid accumulation in the liver which is not due to alcohol use, has emerged as one of the major health problems around the world. The dysregulated lipid metabolism creates a lipotoxic environment which promotes the development of NAFLD, especially the progression from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH). Purposeand Aim This review focuses on the mechanisms of lipid accumulation in the liver, with an emphasis on the metabolic fate of free fatty acids (FFAs) in NAFLD and presents an update on the relevant cellular processes/mechanisms that are involved in lipotoxicity. The changes in the levels of various lipid species that result from the imbalance between lipolysis/lipid uptake/lipogenesis and lipid oxidation/secretion can cause organellar dysfunction, e.g. ER stress, mitochondrial dysfunction, lysosomal dysfunction, JNK activation, secretion of extracellular vesicles (EVs) and aggravate (or be exacerbated by) hypoxia which ultimately lead to cell death. The aim of this review is to provide an overview of how abnormal lipid metabolism leads to lipotoxicity and the cellular mechanisms of lipotoxicity in the context of NAFLD.


2021 ◽  
Vol 22 (3) ◽  
pp. 1458
Author(s):  
Kai Qiu ◽  
Qin Zhao ◽  
Jing Wang ◽  
Guang-Hai Qi ◽  
Shu-Geng Wu ◽  
...  

Metabolic dysfunction-associated fatty liver disease (MAFLD) and its interaction with many metabolic pathways raises global public health concerns. This study aimed to determine the therapeutic effects of Pyrroloquinoline quinone (PQQ, provided by PQQ.Na2) on MAFLD in a chick model and primary chicken hepatocytes with a focus on lipid metabolism, anti-oxidative capacity, and mitochondrial biogenesis. The MAFLD chick model was established on laying hens by feeding them a high-energy low-protein (HELP) diet. Primary hepatocytes isolated from the liver of laying hens were induced for steatosis by free fatty acids (FFA) and for oxidative stress by hydrogen peroxide (H2O2). In the MAFLD chick model, the dietary supplementation of PQQ conspicuously ameliorated the negative effects of the HELP diet on liver biological functions, suppressed the progression of MAFLD mainly through enhanced lipid metabolism and protection of liver from oxidative injury. In the steatosis and oxidative stress cell models, PQQ functions in the improvement of the lipid metabolism and hepatocytes tolerance to fatty degradation and oxidative damage by enhancing mitochondrial biogenesis and then increasing the anti-oxidative activity and anti-apoptosis capacity. At both the cellular and individual levels, PQQ was demonstrated to exert protective effects of hepatocyte and liver from fat accumulation through the improvement of mitochondrial biogenesis and maintenance of redox homeostasis. The key findings of the present study provide an in-depth knowledge on the ameliorative effects of PQQ on the progression of fatty liver and its mechanism of action, thus providing a theoretical basis for the application of PQQ, as an effective nutrient, into the prevention of MAFLD.


2020 ◽  
Vol 21 (12) ◽  
pp. 4534
Author(s):  
Da Eun Kim ◽  
Bo Yoon Chang ◽  
Byeong Min Jeon ◽  
Jong In Baek ◽  
Sun Chang Kim ◽  
...  

A ginsenoside F2-enhanced mixture (SGL 121) increases the content of ginsenoside F2 by biotransformation. In the present study, we investigated the effect of SGL 121 on nonalcoholic fatty liver disease (NAFLD) in vitro and in vivo. High-fat, high-carbohydrate-diet (HFHC)-fed mice were administered SGL 121 for 12 weeks to assess its effect on improving NAFLD. In HepG2 cells, SGL 121 acted as an antioxidant, a hepatoprotectant, and had an anti-lipogenic effect. In NAFLD mice, SGL 121 significantly improved body fat mass; levels of hepatic triglyceride (TG), hepatic malondialdehyde (MDA), serum total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL); and activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In HepG2 cells, induced by oxidative stress, SGL 121 increased cytoprotection, inhibited reactive oxygen species (ROS) production, and increased antioxidant enzyme activity. SGL 121 activated the Nrf2/HO-1 signaling pathway and improved lipid accumulation induced by free fatty acids (FFA). Sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) expression was significantly reduced in NAFLD-induced liver and HepG2 cells treated with SGL 121. Moreover, SGL 121 activated adenosine monophosphate-activated protein kinase (AMPK), which plays an important role in the regulation of lipid metabolism. The effect of SGL 121 on the improvement of NAFLD seems to be related to its antioxidant effects and activation of AMPK. In conclusion, SGL 121 can be potentially used for the treatment of NAFLD.


2021 ◽  
pp. 2719-2730
Author(s):  
Phillip B. Hylemon ◽  
Lianyong Su ◽  
Po‐Cheng Zheng ◽  
Jasmohan S. Bajaj ◽  
Huiping Zhou

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