Luteolin improves non-alcoholic fatty liver disease in db/db mice by inhibition of liver X receptor activation to down-regulate expression of sterol regulatory element binding protein 1c

2017 ◽  
Vol 482 (4) ◽  
pp. 720-726 ◽  
Author(s):  
Ye Yin ◽  
Lu Gao ◽  
Haiyan Lin ◽  
Yue Wu ◽  
Xiao Han ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Regulatory Element ◽  
Receptor Activation ◽  
Liver X Receptor ◽  
Alcoholic Fatty Liver ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Alcoholic Fatty Liver Disease

scholarly journals A Slow-Digesting Carbohydrate Diet during Rat Pregnancy Protects Offspring from Non-Alcoholic Fatty Liver Disease Risk through the Modulation of the Carbohydrate-Response Element and Sterol Regulatory Element Binding Proteins

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 844 ◽  
Author(s):  
Rafael Salto ◽  
Manuel Manzano ◽  
María Dolores Girón ◽  
Ainara Cano ◽  
Azucena Castro ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Regulatory Element ◽  
Liver Lipid ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Sterol Regulatory Element ◽  
Carbohydrate Digestion ◽  
Alcoholic Fatty Liver Disease

High-fat (HF) and rapid digestive (RD) carbohydrate diets during pregnancy promote excessive adipogenesis in offspring. This effect can be corrected by diets with similar glycemic loads, but low rates of carbohydrate digestion. However, the effects of these diets on metabolic programming in the livers of offspring, and the liver metabolism contributions to adipogenesis, remain to be addressed. In this study, pregnant insulin-resistant rats were fed high-fat diets with similar glycemic loads but different rates of carbohydrate digestion, High Fat-Rapid Digestive (HF–RD) diet or High Fat-Slow Digestive (HF–SD) diet. Offspring were fed a standard diet for 10 weeks, and the impact of these diets on the metabolic and signaling pathways involved in liver fat synthesis and storage of offspring were analyzed, including liver lipidomics, glycogen and carbohydrate and lipid metabolism key enzymes and signaling pathways. Livers from animals whose mothers were fed an HF–RD diet showed higher saturated triacylglycerol deposits with lower carbon numbers and double bond contents compared with the HF–SD group. Moreover, the HF–RD group exhibited enhanced glucose transporter 2, pyruvate kinase (PK), acetyl coenzyme A carboxylase (ACC) and fatty acid (FA) synthase expression, and a decrease in pyruvate carboxylase (PyC) expression leading to an altered liver lipid profile. These parameters were normalized in the HF–SD group. The changes in lipogenic enzyme expression were parallel to changes in AktPKB phosphorylation status and nuclear expression in carbohydrate-response element and sterol regulatory element binding proteins. In conclusion, an HF–RD diet during pregnancy translates to changes in liver signaling and metabolic pathways in offspring, enhancing liver lipid storage and synthesis, and therefore non-alcoholic fatty liver disease (NAFLD) risk. These changes can be corrected by feeding an HF–SD diet during pregnancy.

Viral hepatitis and fatty liver disease: how an unwelcome guest makes pâté of the host

2008 ◽  
Vol 416 (2) ◽  
pp. e15-e17 ◽  
Author(s):  
Andrew J. Brown
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Regulatory Element ◽  
Alcoholic Fatty Liver ◽  
Biochemical Journal ◽  
Liver X Receptor Α ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Phosphoinositide 3 Kinase

HBV and HCV (hepatitis B and C viruses respectively) affect hundreds of millions of people globally, and are a major cause of chronic liver disease, including NAFLD (non-alcoholic fatty liver disease). Previous work on HCV-associated fatty liver disease has implicated two transcription factors that are important in lipid metabolism, SREBP1c (sterol-regulatory-element-binding protein 1c) and the LXRα (liver X receptor α). HBV-associated fatty liver disease has been less well-studied. New work from Kim and colleagues in this issue of the Biochemical Journal has provided new insight into how HBV causes fatty liver disease. Investigating HBV's so-called X gene product (HBx), they report that this viral protein directly binds to LXRα in the host liver cells to up-regulate the lipogenic transcription factor, SREBP1c. Also discussed in this commentary is another way that viruses such as HBV and HCV could induce SREBP1c-mediated lipogenesis, via the PI3K (phosphoinositide 3-kinase)–Akt signalling pathway.

scholarly journals Arazyme Suppresses Hepatic Steatosis and Steatohepatitis in Diet-Induced Non-Alcoholic Fatty Liver Disease-Like Mouse Model

2019 ◽  
Vol 20 (9) ◽  
pp. 2325 ◽  
Author(s):  
Hua Li ◽  
Wonbeak Yoo ◽  
Hye-Mi Park ◽  
Soo-Youn Lim ◽  
Dong-Ha Shin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Diet Group ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Arazyme, a metalloprotease from the spider Nephila clavata, exerts hepatoprotective activity in CCL4-induced acute hepatic injury. This study investigated the hepatoprotective effects in high-fat diet (HFD)-induced non-alcoholic fatty liver disease-like C57BL/6J mice. The mice were randomly divided into four groups (n = 10/group): the normal diet group, the HFD group, the arazyme group (HFD with 0.025% arazyme), and the milk thistle (MT) group (HFD with 0.1% MT). Dietary supplementation of arazyme for 13 weeks significantly lowered plasma triglyceride (TG) and non-esterified fatty acid levels. Suppression of HFD-induced hepatic steatosis in the arazyme group was caused by the reduced hepatic TG and total cholesterol (TC) contents. Arazyme supplementation decreased hepatic lipogenesis-related gene expression, sterol regulatory element-binding transcription protein 1 (Srebf1), fatty acid synthase (Fas), acetyl-CoA carboxylase 1 (Acc1), stearoyl-CoA desaturase-1 (Scd1), Scd2, glycerol-3-phosphate acyltransferase (Gpam), diacylglycerol O-acyltransferase 1 (Dgat1), and Dgat2. Arazyme directly reduced palmitic acid (PA)-induced TG accumulation in HepG2 cells. Arazyme suppressed macrophage infiltration and tumor necrosis factor α (Tnfa), interleukin-1β (Il1b), and chemokine-ligand-2 (Ccl2) expression in the liver, and inhibited secretion of TNFα and expression of inflammatory mediators, Tnfa, Il1b, Ccl2, Ccl3, Ccl4, and Ccl5, in PA-induced RAW264.7 cells. Arazyme effectively protected hepatic steatosis and steatohepatitis by inhibiting SREBP-1-mediated lipid accumulation and macrophage-mediated inflammation.

The liver X receptor: A master regulator of the gut–liver axis and a target for non alcoholic fatty liver disease

2013 ◽  
Vol 86 (1) ◽  
pp. 96-105 ◽  
Author(s):  
Simon Ducheix ◽  
Alexandra Montagner ◽  
Vassilia Theodorou ◽  
Laurent Ferrier ◽  
Hervé Guillou
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver X Receptor ◽  
Master Regulator ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals The inhibitory effect of genistein on hepatic steatosis is linked to visceral adipocyte metabolism in mice with diet-induced non-alcoholic fatty liver disease

2010 ◽  
Vol 104 (9) ◽  
pp. 1333-1342 ◽  
Author(s):  
Mi-Hyun Kim ◽  
Kyung-Sun Kang ◽  
Yeon-Sook Lee
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Visceral Fat ◽  
Fatty Liver Disease ◽  
Regulatory Element ◽  
Linear Regression Analysis ◽  
Inhibitory Effect ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) has been deeply associated with visceral adiposity, adipose tissue inflammation and a variety of adipocytokines. We reported previously that genistein inhibited NAFLD by enhancing fatty acid catabolism. However, this molecular approach focused on hepatic metabolism. Thus, we have attempted to determine whether this anti-steatotic effect of genistein is linked to visceral adipocyte metabolism. C57BL/6J mice were fed on normal-fat (NF) diet, high-fat (HF) diet and HF diet supplemented with genistein (1, 2 and 4 g/kg diet) for 12 weeks. Mice fed on the HF diet gained body weight, exhibited increased visceral fat mass and elevated levels of serum and liver lipids, and developed NAFLD, unlike what was observed in mice fed on the NF diet. However, genistein supplementation (2 and 4 g/kg diet) normalised these alternations. In the linear regression analysis, visceral fat (R0·77) and TNFα (R0·62) were strongly correlated with NAFLD among other NAFLD-related parameters. Genistein supplementation suppressed the hypertrophy of adipocytes via the up-regulation of genes involved in fatty acid β-oxidation, including PPARα, 5′-AMP-activated protein kinase and very long-chain acyl CoA dehydrogenase, as well as through the down-regulation of genes associated with adipogenesis or lipogenesis, including liver X receptor-α, sterol-regulatory element-binding protein-1c, PPARγ, retinoid X receptor-α and acetyl CoA carboxylase 2. Moreover, genistein supplementation augmented an anti-steatohepatitic adiponectin TNF and reduced a steatohepatitic TNFα. Collectively, these findings show that genistein may prevent NAFLD via the regulation of visceral adipocyte metabolism and adipocytokines.

scholarly journals A Diet-Induced Pediatric Model of Non Alcoholic Fatty Liver Disease Using Neonatal Iberian Pigs (OR26-02-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Gabriella Hernandez ◽  
Victoria Smith ◽  
Mieko Temple ◽  
Darin Bennet ◽  
Daniel Columbus ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Liver Disease ◽  
Liver Injury ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Binding Protein ◽  
Alcoholic Fatty Liver ◽  
Element Binding Protein ◽  
Alcoholic Fatty Liver Disease

Abstract Objectives The prevalence of non-alcoholic fatty liver disease (NAFLD) in children has increased over the past decades, creating a need for animal models that recapitulate the features of the pediatric disease. Iberian pigs have a leptin-resistant phenotype characterized by hyperleptinemia, hyperphagia, and extreme adipogenesis. We hypothesized that neonatal Iberian pigs fed a high-fat high-fructose (HFF) diet will develop a pattern of liver injury resembling pediatric NAFLD. In addition, we sought to determine if a mixture of probiotics would prevent the disease. Methods Animals were fed 1 of 4 diets containing (g/kg body weight × d) 0 g fructose, 11 g fat and 199 kcal (CON-N; n = 8), 22 g fructose, 16 g fat and 300 kcal (HFF-N; n = 6), CON + probiotic (CON-P; n = 6), or HFF + probiotic (HFF-P; n = 6) every 6 h for 70 d. The probiotic mixture (6.2 × 104cfu/mL) contained Pediococcus, Lactobacillus and Bacillus. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 65 at 2 h post feeding. Fasting leptin, insulin, glucose and homeostatic model assessment (HOMA) values were assessed on d 70. Liver tissue was collected on d 70 for histology, triacylglyceride (TG) quantification, and gene expression of tumor necrosis factor (TNF) α, tumor growth factor (TGF) β, interleukin (IL) 1α, peroxisome proliferator-activated receptor (PPAR) γ, carbohydrate-responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein (SREBP) 1c. Results Body weight was higher in CON-P, and insulin and HOMA values in HFF-P and CON-P (P ≤ 0.05). Leptin, alanine and aspartate aminotransferases, alkaline phosphatase, lactate dehydrogenase and total bilirubin were increased (P ≤ 0.001), and high and low density lipoproteins decreased (P ≤ 0.05) in HFF-N and HFF-P. Livers in HFF-P and HFF-N had higher relative weight and TG (P ≤ 0.001), micro and macrovesicular steatosis, ballooning degeneration, Mallory-denk bodies, inflammation and necrosis, increased gene expression of TNFα, TGFβ, IL1α and PPARγ (P ≤ 0.001), and decreased ChREBP (P ≤ 0.001). Conclusions Iberian pigs fed a HFF diet recapitulate many pediatric NAFLD-associated features, in the absence of obesity and independently of probiotic supplementation, suggesting a potentially suitable model for pediatric NAFLD research. Funding Sources ARI, AcornSeekers.

Increased serum liver X receptor ligand oxysterols in patients with non-alcoholic fatty liver disease

2012 ◽  
Vol 47 (11) ◽  
pp. 1257-1266 ◽  
Author(s):  
Tadashi Ikegami ◽  
Hideyuki Hyogo ◽  
Akira Honda ◽  
Teruo Miyazaki ◽  
Katsutoshi Tokushige ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver X Receptor ◽  
Receptor Ligand ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease
Sign in / Sign up

Export Citation Format

Share Document