scholarly journals Update on Berberine in Nonalcoholic Fatty Liver Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yang Liu ◽  
Li Zhang ◽  
Haiyan Song ◽  
Guang Ji
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Biological Activities ◽  
Adenosine Monophosphate ◽  
Experimental Models ◽  
Nonalcoholic Fatty Liver ◽  
Ampk Signaling

Berberine (BBR), an active ingredient from nature plants, has demonstrated multiple biological activities and pharmacological effects in a series of metabolic diseases including nonalcoholic fatty liver disease (NAFLD). The recent literature points out that BBR may be a potential drug for NAFLD in both experimental models and clinical trials. This review highlights important discoveries of BBR in this increasing disease and addresses the relevant targets of BBR on NAFLD which links to insulin pathway, adenosine monophosphate-activated protein kinase (AMPK) signaling, gut environment, hepatic lipid transportation, among others. Developing nuanced understanding of the mechanisms will help to optimize more targeted and effective clinical application of BBR for NAFLD.

Hepatic AMP Kinase as a Potential Target for Treating Nonalcoholic Fatty Liver Disease: Evidence from Studies of Natural Products

2018 ◽  
Vol 25 (8) ◽  
pp. 889-907 ◽  
Author(s):  
Gang Xu ◽  
Kaixun Huang ◽  
Jun Zhou
Keyword(s):  
Natural Products ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Adenosine Monophosphate ◽  
Protective Effects ◽  
Nonalcoholic Fatty Liver ◽  
Ampk Signaling ◽  
Downstream Effectors

Background: Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is the leading cause of cryptogenic cirrhosis and has consistently been implicated in related metabolic disorders, such as dyslipidemia and type 2 diabetes (T2D). However, the pathogenesis of NAFLD remains to be elucidated, and no established therapeutic regimens for treating NAFLD exist. Adenosine monophosphate (AMP)-activated protein kinase (AMPK), the main cellular energy sensor, has been implicated as a key regulator of hepatic lipid and glucose metabolism. Recently, emerging evidence indicates that many plant-derived natural products are capable of ameliorating NAFLD by targeting AMPK. Methods: The published literature in PubMed relating to this topic was searched through June 2016. Results: Significant advances have been made with respect to understanding the protective effects of plant-derived natural products against NAFLD. A variety of natural products, including alkaloids (berberine, demethyleneberberine, nicotine, caffeine, etc.), polyphenols (resveratrol, puerarin, curcumin, caffeic acid, etc.) and other compounds (β- caryophyllene, gastrodin, compound K, betulinic acid, etc.), have demonstrated promising results in preclinical studies. Mechanistic studies of these compounds have focused on their activation of AMPK and its downstream effectors involved in lipid metabolism. Conclusion: The findings of this review confirm that plant-derived natural products capable of activating the AMPK signaling pathway are potential therapeutic agents for NAFLD.

scholarly journals Circ_0057558 promotes nonalcoholic fatty liver disease by regulating ROCK1/AMPK signaling through targeting miR-206

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Xi Chen ◽  
Qing-Qing Tan ◽  
Xin-Rui Tan ◽  
Shi-Jun Li ◽  
Xing-Xing Zhang
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Luciferase Assay ◽  
Nonalcoholic Fatty Liver ◽  
Ampk Signaling ◽  
Related Proteins

AbstractNonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders that is featured by the extensive deposition of fat in the hepatocytes. Current treatments are very limited due to its unclear pathogenesis. Here, we investigated the function of circ_0057558 and miR-206 in NAFLD. High-fat diet (HFD) feeding mouse was used as an in vivo NAFLD model and long-chain-free fatty acid (FFA)-treated liver cells were used as an in vitro NAFLD model. qRT-PCR was used to measure levels of miR-206, ROCK1 mRNA, and circ_0057558, while Western blotting was employed to determine protein levels of ROCK1, p-AMPK, AMPK, and lipogenesis-related proteins. Immunohistochemistry were performed to examine ROCK1 level. Oil-Red O staining was used to assess the lipid deposition in cells. ELISA was performed to examine secreted triglyceride (TG) level. Dual-luciferase assay was used to validate interactions of miR-206/ROCK1 and circ_0057558/miR-206. RNA immunoprecipitation was employed to confirm the binding of circ_0057558 with miR-206. Circ_0057558 was elevated while miR-206 was reduced in both in vivo and in vitro NAFLD models. miR-206 directly bound with ROCK1 3’-UTR and suppressed lipogenesis and TG secretion through targeting ROCK1/AMPK signaling. Circ_0057558 directly interacted with miR-206 to disinhibit ROCK1/AMPK signaling. Knockdown of circ_0057558 or overexpression of miR-206 inhibited lipogenesis, TG secretion and expression of lipogenesis-related proteins. ROCK1 knockdown reversed the effects of circ_0057558 overexpression. Injection of miR-206 mimics significantly ameliorated NAFLD progression in vivo. Circ_0057558 acts as a miR-206 sponge to de-repress the ROCK1/AMPK signaling and facilitates lipogenesis and TG secretion, which greatly contributes to NAFLD development and progression.

scholarly journals Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Peng Yu ◽  
Xi Xu ◽  
Jing Zhang ◽  
Xuan Xia ◽  
Fen Xu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Ampk Signaling

A glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LR) had been experimentally and clinically shown to ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the beneficial effect of LR on NAFLD in vivo and in vitro and its underlying molecular mechanism. The effects of LR were examined on the high-fat diet-induced in vivo model in mice and in vitro model of NAFLD in human HepG2 cells. Liver tissues and HepG2 cells were procured for measuring lipid metabolism, histological examination, and western blot analysis. LR administration significantly lowered the serum lipid profile and lipid disposition in vitro and in vivo because of the altered expression of enzymes on hepatic gluconeogenesis and lipid metabolism. Moreover, LR significantly decreased Src homology region 2 domain-containing phosphatase-1 (SHP1) and then increased the expression of phosphorylated-AMP-activated protein kinase (p-AMPK). However, the overexpression of SHP1 mediated by lentivirus vector reversed LR-induced improvement in lipid deposition. Moreover, SHP1 silencing could further increase the expression of p-AMPK to ameliorate lipid metabolism and relative lipogenic gene induced by LR. In addition, abrogation of AMPK by Compound C eliminated the protective effects of LR on lipid metabolism without changing the expression of SHP1. LR markedly prevented NAFLD through adjusting lipid metabolism via SHP1/AMPK signaling pathway.

scholarly journals Targeted Nutrient Modifications in Purified Diets Differentially Affect Nonalcoholic Fatty Liver Disease and Metabolic Disease Development in Rodent Models

2020 ◽  
Vol 4 (6) ◽  
Author(s):  
Sridhar Radhakrishnan ◽  
Jia-Yu Ke ◽  
Michael A Pellizzon
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Complex Spectrum ◽  
Disease Development ◽  
Rodent Models ◽  
Nonalcoholic Fatty Liver ◽  
Time Frames

ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is a complex spectrum of disorders ranging from simple benign steatosis to more aggressive forms of nonalcoholic steatohepatitis (NASH) and fibrosis. Although not every patient with NAFLD/NASH develops liver complications, if left untreated it may eventually lead to cirrhosis and hepatocellular carcinoma. Purified diets formulated with specific nutritional components can drive the entire spectrum of NAFLD in rodent models. Although they may not perfectly replicate the clinical and histological features of human NAFLD, they provide a model to gain further understanding of disease progression in humans. Owing to the growing demand of diets for NAFLD research, and for our further understanding of how manipulation of dietary components can alter disease development, we outlined several commonly used dietary approaches for rodent models, including mice, rats, and hamsters, time frames required for disease development and whether other metabolic diseases commonly associated with NAFLD in humans occur.

scholarly journals Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanism and Therapy

2017 ◽  
Author(s):  
Junli Ma ◽  
Qihang Zhou ◽  
Houkai Li
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Targeted Therapies ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Herbal Medicines ◽  
Active Components ◽  
Nonalcoholic Fatty Liver

Gut microbiota play critical roles in development of obese-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, and insulin resistance, which highlighted the potential of gut microbiota-targeted therapies on these diseases. There are various ways that can manipulate gut microbiota including probiotics, prebiotics, synbiotics, antibiotics and some active components from herbal medicines. In this review, we first reviewed the main roles of gut microbiota in mediating the development of NAFLD, and the advances in gut microbiota-targeted therapies on NAFLD in both the experimental and clinical studies, as well as the conclusions on the prospect of gut microbiota-targeted therapies in the future.

scholarly journals Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanism and Therapy

2017 ◽  
Author(s):  
Junli Ma ◽  
Qihang Zhou ◽  
Houkai Li
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Targeted Therapies ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Herbal Medicines ◽  
Active Components ◽  
Nonalcoholic Fatty Liver

Gut microbiota play critical roles in development of obese-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, and insulin resistance, which highlighted the potential of gut microbiota-targeted therapies on these diseases. There are various ways that can manipulate gut microbiota including probiotics, prebiotics, synbiotics, antibiotics and some active components from herbal medicines. In this review, we first described the main roles of gut microbiota in mediating the development of NAFLD, and the advances in gut microbiota-targeted therapies in NAFLD in both the experimental and clinical studies, as well as the conclusions on the prospect of gut microbiota-targeted therapies in the future.

scholarly journals 5-ALA ameliorates hepatic steatosis through AMPK signaling pathway

2017 ◽  
Vol 59 (2) ◽  
pp. 121-128 ◽  
Author(s):  
Haoyong Yu ◽  
Mingliang Zhang ◽  
Yunqin Ma ◽  
Junxi Lu ◽  
Jiemin Pan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Signaling Pathway ◽  
Fatty Liver Disease ◽  
Aminolevulinic Acid ◽  
Therapeutic Effects ◽  
Nonalcoholic Fatty Liver ◽  
Ampk Signaling

5-Aminolevulinic acid (5-ALA), the first compound in the porphyrin synthesis pathway, has been reported to ameliorate the diabetic state in Otsuka Long-Evans Tokushima Fatty rats by reducing fat pad weight in the retroperitoneal region. Dietary supplementation with 5-ALA has additionally demonstrated the capacity to lower blood glucose and HbA1c levels among subjects with diabetes. The etiology of nonalcoholic fatty liver disease (NAFLD) is complex and its typical characteristics include obesity and insulin resistance. As 5-ALA supplementation has previously normalized glucose and insulin resistance, we sought to investigate whether 5-ALA had potential therapeutic effects on NAFLD and elucidate the signal pathway mediating these effects. To explore these questions, we fed C57BL/6J mice a high-fat diet (HFD) to induce a fatty liver disease and supplemented the diet-induced obese (DIO) mice with 5-ALA. The mice in the presence of 5-ALA demonstrated a decrease in body weight and hepatic lipid content and moderate improvement in glucose homeostasis compared to untreated controls. Further, we found that 5-ALA activated AMPK signaling pathway, which was correlated with enhanced lipolysis and fatty acid β-oxidation. Human hepatocarcinoma cells (HepG2 cells) treated with 5-ALA were additionally used to investigate the mechanics of 5-ALA. Treated cells had a higher expression of lipolysis-related genes, including PGC-1α. Our data indicated that 5-ALA might represent a novel compound that could be useful for the treatment of nonalcoholic fatty liver disease (NAFLD), likely through the restoration of phosphorylation levels of AMPK (Thr172) and acetyl-CoA (ACC) (Ser79), further enhanced PGC1α and CPT1α expression.

scholarly journals Herbal therapy for ameliorating nonalcoholic fatty liver disease via rebuilding the intestinal microecology

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xiao-Fang Yang ◽  
Ming Lu ◽  
Lijiao You ◽  
Huan Gen ◽  
Lin Yuan ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Intestinal Microbiota ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Herbal Medicines ◽  
Nonalcoholic Fatty Liver ◽  
Promising Target ◽  
Effective Performance

AbstractThe worldwide prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing, and this metabolic disorder has been recognized as a severe threat to human health. A variety of chemical drugs have been approved for treating NAFLD, however, they always has serious side effects. Chinese herbal medicines (CHMs) have been widely used for preventing and treating a range of metabolic diseases with satisfactory safety and effective performance in clinical treatment of NAFLD. Recent studies indicated that imbanlance of the intestinal microbiota was closely associated with the occurrence and development of NAFLD, thus, the intestinal microbiota has been recognized as a promising target for treatment of NAFLD. In recent decades, a variety of CHMs have been reported to effectively prevent or treat NAFLD by modulating intestinal microbiota to further interfer the gut-liver axis. In this review, recent advances in CHMs for the treatment of NAFLD via rebuilding the intestinal microecology were systematically reviewed. The key roles of CHMs in the regulation of gut microbiota and the gut-liver axis along with their mechanisms (such as modulating intestinal permeability, reducing the inflammatory response, protecting liver cells, improving lipid metabolism, and modulating nuclear receptors), were well summarized. All the knowledge and information presented here will be very helpful for researchers to better understand the applications and mechanisms of CHMs for treatment of NAFLD.

Abstract 371: Deficiency in Microrna-155 Leads to Reduced Atherosclerosis, Increased Obesity and Nonalcoholic Fatty Liver Disease--A Novel Mouse Model of Metabolically Healthy Obesity

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Candice Johnson ◽  
Anthony Virtue ◽  
Jahaira Lopez-Pastraña ◽  
Ying Shao ◽  
Hangfei Fu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Metabolically Healthy Obesity ◽  
Nonalcoholic Fatty Liver ◽  
Fed State ◽  
Metabolically Healthy

Metabolically healthy obesity (MHO) describes the phenomenon of overweight and obese patients paradoxically retaining a healthy metabolic profile. The molecular mechanisms underlying MHO remain enigmatic partly due to a dearth of animal models mirroring MHO in patients. Using apolipoprotein E knockout (ApoE -/- ) mice on high-fat (HF) diet as an atherosclerotic obesity model, we demonstrated: 1) microRNA-155 (miRNA-155, miR-155) is significantly upregulated in aortas of ApoE -/- mice; and miR-155 deficiency in ApoE -/- mice inhibits atherosclerosis; 2) ApoE -/- /miR-155 -/- (DKO) mice show HF diet-induced obesity, adipocyte hypertrophy and present with nonalcoholic fatty liver disease (NAFLD); 3) DKO mice demonstrate HF diet-induced elevations of plasma leptin, resistin, fed-state and fasting insulin, increased expression of adipogenic transcription factors, but lack glucose intolerance and insulin resistance. Our results are the first to present a metabolically healthy obesity (MHO) model using DKO mice with features of decreased atherosclerosis, increased obesity and NAFLD. Our findings suggest the mechanistic role of reduced miR-155 expression in MHO and present a new MHO working model based on a single miRNA deficiency in diet-induced obese atherogenic mice. Furthermore, our results serve as a breakthrough in understanding the potential mechanism underlying MHO and provide a new biomarker and novel therapeutic target for MHO-related metabolic diseases.

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