scholarly journals Regulation of Lipid and Glucose Metabolism in Hepatocytes by Phytochemicals from Coffee By-Products and Prevention of Non-Alcoholic Fatty Liver Disease In Vitro

Proceedings ◽  
2020 ◽  
Vol 61 (1) ◽  
pp. 20
Author(s):  
Miguel Rebollo-Hernanz ◽  
Yolanda Aguilera ◽  
Maria A. Martin-Cabrejas ◽  
Elvira Gonzalez de Mejia
Keyword(s):  
Liver Disease ◽  
Glucose Metabolism ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Aqueous Extracts ◽  
Alcoholic Fatty Liver ◽  
Coffee Husk ◽  
By Products ◽  
Alcoholic Fatty Liver Disease

This study aimed to assess the effect of the primary phytochemicals from coffee by-products and two aqueous extracts from the coffee husk and silverskin on lipid and glucose metabolism regulation in hepatocytes using an in vitro model of non-alcoholic fatty liver disease. Coffee husk and silverskin were used to prepare two aqueous extracts (CHE and CSE, respectively) using water. The phytochemical composition was determined using UPLC-MS/MS analysis. HepG2 cells were co-treated with 10–50 µmol L‒1 of either pure caffeine, chlorogenic acid, caffeic acid, protocatechuic acid, or gallic acid, and kaempferol, CHE, or CSE (20–100 µg mL‒1) in the presence or absence of palmitic acid (PA, 500 µmol L‒1). Different biomarkers of cell metabolism were assessed 24 h after the co-treatment in cell supernatants and lysates using chemical, biochemical, and immunochemical techniques. Phytochemicals from coffee by-products decreased PA-triggered lipid accumulation (16–94%, p < 0.05) by reducing fatty acid synthase activity and stimulating lipolysis (8–83%, p < 0.05). CHE, CSE, and therein-bioactive compounds promoted glucose uptake (13–45%) via the increase in the phosphorylation of the insulin receptor (1.9- to 2.7-fold), protein kinase B (AKT) (1.4- to 3.1-fold), AMPKα (1.6- to 2.4-fold), and PTEN (2.0- to 4.2-fold). In conclusion, our results proved that phytochemicals from coffee by-products, mainly caffeine and chlorogenic acid, could regulate hepatic lipid and glucose metabolism. Overall, our results generate new insights into the use of coffee by-products as a sustainable food ingredient to encounter non-alcoholic fatty liver disease.

scholarly journals Effects of Oral Vitamin C Supplementation on Liver Health and Associated Parameters in Patients With Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhangya He ◽  
Xiaomin Li ◽  
Hexiang Yang ◽  
Pei Wu ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Glucose Metabolism ◽  
Vitamin C ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Hmw Adiponectin ◽  
Liver Health ◽  
Glutamyl Transferase ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent hepatic disorder worldwide, and an unhealthy lifestyle is the leading risk factor for its occurrence. Vitamin C (VC) has been suggested to protect NAFLD, whereas evidence from randomized controlled trials (RCTs) is sparse. In this study, we aimed to investigate the potential benefits of VC supplementation daily on liver health and associated parameters in patients with NAFLD. In this double-blind, RCT, 84 patients with NAFLD, aged 18–60 years old, were assigned to 12 weeks of oral treatment with either low (250 mg/day, n = 26), medium (1,000 mg/day, n = 30), or high (2,000 mg/day, n = 28) doses of VC supplements. After the intervention, the Medium group had a more significant decrease in aspartate aminotransferase [Medium, −5.00 (−10.25, −1.75) vs. High, −2.50 (−7.75, 0.00), P = 0.02] and alanine aminotransferase [Medium, −8.00 (−18.00, −1.75) vs. High, −3.50 (−13.75, 4.25), P = 0.05; Medium vs. Low, −3.00 (−9.00, 5.50), P = 0.031]. The levels of other indicators of liver health, such as gamma-glutamyl transferase, alkaline phosphatase, total bilirubin, and direct bilirubin were decreased after the intervention but comparable among the three groups and so did the parameters of glucose metabolism, such as fasting insulin, fasting glucose, and homeostasis model assessment for insulin resistance. The plasma level of VC in patients and total adiponectin and high molecular weight (HMW) adiponectin levels were also elevated but not in a dose-dependent manner. Meanwhile, analysis of fecal microbiota composition showed an increase in the alpha diversity (Abundance-based Coverage Estimator (ACE), Shannon, chao1, and Simpson) both in the Low and the Medium groups. A total of 12 weeks of VC supplementation, especially 1,000 mg/day, improved liver health and glucose metabolism in patients with NAFLD. The elevated plasma levels of VC, total and HMW adiponectin, and the improvement of intestinal microbiota may have made some contributions.

Relationship between non-alcoholic fatty liver disease during pregnancy and abnormal glucose metabolism during and after pregnancy

2019 ◽  
Vol 68 (3) ◽  
pp. 743-747
Author(s):  
Maryam Sattari ◽  
Fernando Bril ◽  
Robert Egerman ◽  
Srilaxmi Kalavalapalli ◽  
Kenneth Cusi
Keyword(s):  
Diabetes Mellitus ◽  
Liver Disease ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Post Partum ◽  
Alcoholic Fatty Liver ◽  
Abnormal Glucose Metabolism ◽  
Alcoholic Fatty Liver Disease

While non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of impaired glucose tolerance and type 2 diabetes mellitus (DM) in non-pregnant patients, the clinical significance of NAFLD during pregnancy is still unclear. We hypothesized that sonographic findings of NAFLD during pregnancy would be associated with gestational diabetes mellitus (GDM) and predict abnormal postpartum glucose metabolism. NAFLD was assessed by ultrasound during and after pregnancy. Standard 2-hour 75 g oral glucose tolerance test (OGTT) was used during pregnancy and post partum to establish GDM and the diagnosis of normal, impaired fasting glucose, or DM. We also measured plasma insulin, C peptide, and free fatty acids (FFA) concentration during an OGTT to evaluate glucose tolerance, insulin secretion and insulin resistance. Of the 84 subjects, 12 had sonographic evidence of NAFLD (5 of whom had OGTT post partum). There was a non-significant trend toward higher mean weight and body mass index during and after gestation in the NAFLD group, but no statistically significant differences in mean age, ethnicity, prepregnancy and postpregnancy hemoglobin A1C values, and postpartum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, insulin, or FFA. We did not find an association between sonographic evidence of NAFLD during the third trimester of pregnancy and abnormal glucose metabolism during or after pregnancy. This study also suggests that while AST and ALT are not reliable diagnostic tools for NAFLD during the postpartum period, ultrasound is a reasonably safe, practical, and cost-effective modality to assess maternal hepatic fat during pregnancy.

scholarly journals Bicyclol Regulates Hepatic Gluconeogenesis in Rats with Type 2 Diabetes and Non-alcoholic Fatty Liver Disease by Inhibiting Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Hongxue Li ◽  
Qian Xu ◽  
Chengye Xu ◽  
Yuxin Hu ◽  
Xingyang Yu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Liver Disease ◽  
Glucose Metabolism ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Glucose Metabolism Disorders ◽  
Liver Inflammation ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Hepatic gluconeogenesis plays an important role in maintaining the body’s glucose metabolism homeostasis. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases, when combined with type 2 diabetes mellitus (T2DM), it can cause severe glucose metabolism disorders. Studies have confirmed that chronic liver inflammatory lesions are the basis of T2DM combined with NAFLD (T2DM–NAFLD), inhibiting liver inflammation can improve glucose metabolism disorders. It is essential to explore safe and effective drugs to inhibit liver inflammation to improve the body’s glucose metabolism disorders. Bicyclol is a biphenyl derivative that has anti-oxidative and anti-inflammatory properties. In the present study, the hepatoprotective effects and underlying mechanisms of bicyclol in T2DM–NAFLD were investigated, and T2DM–NAFLD with/without bicyclol treatment models were established. The results revealed that bicyclol alleviated fasting blood glucose, serum transaminase levels, insulin resistance, hepatic adipogenesis, lipid accumulation and markedly reduced T2DM–NAFLD rat histological alterations of livers. Not only that, bicyclol markedly attenuated T2DM–NAFLD induced production of inflammation factors (IL-1β and TNF-α). Moreover, bicyclol suppressed the expression of insulin/gluconeogenesis signaling pathway (Akt, PGC-1α and PEPCK). These findings suggested that bicyclol might be a potentially effective drug for the treatment of T2DM–NAFLD and other metabolic disorders.

scholarly journals Naringin protects against non-alcoholic fatty liver disease by promoting autophagic flux and lipophagy

2021 ◽  
Author(s):  
Lingling Guan ◽  
Lan Guo ◽  
Heng Zhang ◽  
Hao Liu ◽  
Yuan Qiao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Autophagic Flux ◽  
Mechanism Study ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Background and Purpose: The autophagic degradation of lipid droplets (LDs), termed lipophagy, is the main mechanism contributing to lipid consumption in hepatocytes. The identification of effective and safe natural compounds that target lipophagy to eliminate excess lipids may be a potential therapeutic strategy for non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effects of naringin on NAFLD and the underlying mechanism. Experimental Approach: The role of naringin was investigated in mice fed a high-fat diet (HFD) to induce NAFLD, as well as in AML12 cells and primary hepatocytes stimulated by palmitate (PA). Transcription factor EB (TFEB)-knockdown AML12 cells and hepatocyte-specific TFEB-knockout mice were also used for the mechanism study. In vivo and in vitro studies were conducted using transmission electron microscopy, immunofluorescence techniques and western blot analysis. Key Results: We found that naringin treatment effectively relieved HFD-induced hepatic steatosis in mice and inhibited palmitate (PA)-induced lipid accumulation in hepatocytes. The increased p62 and LC3-II levels observed with excess lipid-support autophagosome accumulation and impaired autophagic flux. Treatment with naringin restored TFEB-mediated lysosomal biogenesis, thereby promoting the fusion of autophagosomes and lysosomes, restoring impaired autophagic flux and further inducing lipophagy. However, the knockdown of TFEB in hepatocytes or the hepatocyte-specific knockout of TFEB in mice abrogated naringin-induced lipophagy, which eliminated the therapeutic effect of naringin on hepatic steatosis. Conclusion and Implications: These results demonstrate that TFEB-mediated lysosomal biogenesis and subsequent lipophagy play essential roles in the ability of naringin to mitigate hepatic steatosis and suggest that naringin is a promising drug for treating or relieving NAFLD.

scholarly journals Integrated gut–liver-on-a-chip platform as an in vitro human model of non-alcoholic fatty liver disease

2020 ◽  
Author(s):  
Jiandong Yang ◽  
Yoshikazu Hirai ◽  
Kei Iida ◽  
Shinji Ito ◽  
Marika Trumm ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Cellular Response ◽  
Liver Cells ◽  
Human Model ◽  
Gene Expressions ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) afflicts a large percentage of the population, but no effective treatments have been established so far because of the unsuitability of in vitro assays and experimental models using animals. By co-culturing human gut and liver cell lines interconnected via microfluidics for a closed circulation loop, we created a gut–liver-on-a-chip (iGLC) platform as an in vitro human model of the gut–liver axis (GLA) for the initiation and progression of NAFLD. Microscopic high-content analysis followed by mRNA sequencing showed that co-culturing the gut and liver cells significantly affected each cell type compared to culturing them separately. NAFLD-inducing free fatty acids (FFAs) accumulated in the gut cells and elevated gene expressions associated with retinol metabolism and glucuronidation. The FFA-treated liver cells accumulated intracellular lipid droplets and showed an increase in gene expressions associated with a cellular response to copper ions and endoplasmic reticulum stress. As an in vitro human GLA model, the iGLC platform may serve as an alternative to animal experiments for investigating NAFLD mechanisms.

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