scholarly journals Effects of Epeleuton, a Novel Synthetic Second‐Generation n‐3 Fatty Acid, on Non‐Alcoholic Fatty Liver Disease, Triglycerides, Glycemic Control, and Cardiometabolic and Inflammatory Markers

2020 ◽  
Vol 9 (16) ◽  
Author(s):  
John Climax ◽  
Philip N. Newsome ◽  
Moayed Hamza ◽  
Markus Weissbach ◽  
David Coughlan ◽  
...  

Background Epeleuton is 15‐hydroxy eicosapentaenoic acid ethyl ester, a second‐generation synthetic n‐3 fatty acid derivative of eicosapentaenoic acid. The primary objective was to assess the effect of epeleuton on markers of nonalcoholic fatty liver disease (NAFLD) with post hoc analyses of cardiometabolic markers. Methods and Results In a multicenter, randomized, double‐blind, placebo‐controlled trial, 96 adults with nonalcoholic fatty liver disease and body mass index 25 to 40 were randomized in a 1:1:1 ratio to receive epeleuton 2 g/day, epeleuton 1 g/day, or placebo for 16 weeks. A total of 27% of patients had diabetes mellitus. Primary end points of changes in alanine aminotransferase and liver stiffness did not improve at week 16. Secondary and post hoc analyses investigated changes in cardiometabolic markers. Epeleuton 2 g/day significantly decreased triglycerides, very‐low‐density lipoprotein cholesterol, and total cholesterol without increasing low‐density lipoprotein cholesterol. Despite a low mean baseline hemoglobin A1C (HbA 1C ; 6.3±1.3%), epeleuton 2 g/day significantly decreased HbA 1c (−0.4%; P =0.026). Among patients with baseline HbA 1c >6.5%, epeleuton 2 g/day decreased HbA 1c by 1.1% ( P =0.047; n=26). Consistent dose‐dependent reductions were observed for fasting plasma glucose, insulin, and insulin resistance indices. Epeleuton 2 g/day decreased circulating markers of cardiovascular risk and endothelial dysfunction. Epeleuton was well tolerated, with a safety profile not different from placebo. Conclusions While epeleuton did not meet its primary end points on alanine aminotransferase or liver stiffness, it significantly decreased triglycerides, HbA 1C , plasma glucose, and inflammatory markers. These data suggest epeleuton may have potential for cardiovascular risk reduction and nonalcoholic fatty liver disease by simultaneously targeting hypertriglyceridemia, hyperglycemia, and systemic inflammation. Further trials are planned. Registration URL: https://www.clini​caltr​ials.gov ; Unique identifier: NCT02941549.

2016 ◽  
Vol 36 (8) ◽  
pp. 1213-1220 ◽  
Author(s):  
Zhenghui G. Jiang ◽  
Elliot B. Tapper ◽  
Margery A. Connelly ◽  
Carolina F. M. G. Pimentel ◽  
Linda Feldbrügge ◽  
...  

Cholesterol ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Dimitrios Papandreou ◽  
Zaharoula Karabouta ◽  
Israel Rousso

Background. Nonalcoholic fatty liver disease (NAFLD) in children has been recognized as a major health burden. Serum lipids as well as dietary cholesterol (DC) intake may positively relate to development of NAFLD. The purpose of this study was to investigate anthropometric, biochemical, and dietary intake parameters of obese Greek children with and without NAFLD. Materials and Methods. Eighty-five obese children aged 8–15 (45 boys/40 girls) participated in the study. NAFLD was diagnosed by ultrasonography (US) in all subjects. Liver indexes were measured in all children. A 3-day dietary was recorded for all subjects. Results. 38 out of 85 children (44.7%) were found to have fatty liver. Obese children with increased levels of TC (95% CI: 1.721–3.191), low density lipoprotein (LDL) (95% CI: 1.829–3.058), and increased dietary cholesterol intakes (95% CI: 1.511–2.719) were 2.541, 2.612, and 2.041 times more likely to develop NAFLD compared with the children without NAFLD. Conclusion. The present study showed that TC, LDL, and DC were the strongest risk factors of development of NAFLD. Reducing body weight and dietary cholesterol intakes as well as decreasing serum TC and LDL levels are urgently necessary in order to prevent NAFLD and possible other health implications later in life.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ying Li ◽  
Jinyan Zhao ◽  
Haiyin Zheng ◽  
Xiaoyong Zhong ◽  
Jianheng Zhou ◽  
...  

Total alkaloids inRubus aleaefolius Poir(TARAP) is a folk medicinal herb that has been used clinically in China to treat nonalcoholic fatty liver disease (NAFLD) for many years. However, the mechanism of its anti-NAFLD effect is largely unknown. In this study, we developed a NAFLD rat model by supplying a modified high-fat diet (mHFD)ad libitumfor 8 weeks and evaluated the therapeutic effect of TARAP in NAFLD rats as well as the underlying molecular mechanism. We found that TARAP could reduce the serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL-C) levels and increase the serum high-density lipoprotein (HDL-C) level in NAFLD rats. In addition, TARAP treatment reduced expression of fatty acid synthetase (FAS), and acetyl-CoA carboxylase (ACC) and upregulated the expression of carnitine palmitoyltransferase (CPT). Our results suggest that regulation of lipid metabolism may be a mechanism by which TARAP treats NAFLD.


2021 ◽  
Vol 11 (3) ◽  
pp. 730-735
Author(s):  
Jiandun Li ◽  
Dingyu Yang ◽  
Ting Chen ◽  
Tao Li ◽  
Peng Jiang ◽  
...  

Background: Nonalcoholic fatty liver disease (NAFLD) increases the possibility to suffer from liver or cardiovascular disease. Although hepatic biopsy is well acknowledged as the standard diagnosis, it is difficult to implement because of its intrusiveness and cost concerns. Moreover, overweight people or diabetic patients are always NAFLD-positive, but not absolute. Therefore, to distinguish whether a diabetic case has NAFLD via nonintrusive indicators is of great significance for further interventions. Objective: With 8499 diabetic patients hosted by Shanghai Sixth People’s Hospital, we try to rank the impacts of multiple routine indicators (features) on NAFLD, and further predict NAFLD within this diabetic population. Methods: We first rank dozens of related features according to their contributions in NAFLD prediction, and then we prune several trivial features to simplify the prediction. Additionally, three classification algorithms are considered and compared, e.g., C4.5, Naïve Bayes and Random Forest. Results: The experiment shows that Random Forest outperforms the rest (accuracy 85.1%, recall 90.98% and AUC 0.631). Conclusions: We find that the top nine markers together can effectively tell NAFLD out of this diabetic population. They are triglyceride (TG), low density lipoprotein (LDL), insulin (INS), hbA1C, high-density lipoprotein (HDL), fasting plasma glucose (FPG), age, total cholesterol (TC) and duration.


10.23856/4627 ◽  
2021 ◽  
Vol 46 (3) ◽  
pp. 208-214
Author(s):  
Olesia Bochar ◽  
Volodymyr Bochar

This research was aimed to estimate the course of hypertension on the background of obesity and nonalcoholic fatty liver disease according to its stages (steatosis and steatohepatitis). Ninety patients were evaluated for anthropometric, general-clinical, laboratory, instrumental and immune-enzymatic research methods. With USG, the most characteristic features of fatty liver infiltration and the criteria for the distinction of steatosis from steatohepatitis were revealed, and on the basis of them 2 groups were formed. Thus, the progression of nonalcoholic fatty liver disease to the stage of steatohepatitis was accompanied by a more pronounced increase in blood pressure larger in comparison with steatosis of mass index of myocardium and anterior-posterior size of the left atrium, indicating the progression of structural myocardial disorders. Therefore, the presence of non-alcoholic steatohepatitis in patients with hypertension can be regarded as unfavorable prognostic criteria for the development of heart failure. In the presence of steatohepatitis, more marked changes in lipidograms were noticed for Low-Density Lipoprotein and Triglyceride values and a violation of the functional state of the liver with a cytolytic syndrome on the activity of AST and ALT and the total bilirubin, which may contribute to the progression of liver damage.


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.


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