scholarly journals Effects of a Low Dose of Caffeine Alone or as Part of a Green Coffee Extract, in a Rat Dietary Model of Lean Non-Alcoholic Fatty Liver Disease without Inflammation

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3240
Author(s):  
Ana Magdalena Velázquez ◽  
Núria Roglans ◽  
Roger Bentanachs ◽  
Maria Gené ◽  
Aleix Sala-Vila ◽  
...  
Keyword(s):  
Liver Disease ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Low Dose ◽  
Female Rats ◽  
Green Coffee ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease is a highly prevalent condition without specific pharmacological treatment, characterized in the initial stages by hepatic steatosis. It was suggested that lipid infiltration in the liver might be reduced by caffeine through anti-inflammatory, antioxidative, and fatty acid metabolism-related mechanisms. We investigated the effects of caffeine (CAF) and green coffee extract (GCE) on hepatic lipids in lean female rats with steatosis. For three months, female Sprague-Dawley rats were fed a standard diet or a cocoa butter-based high-fat diet plus 10% liquid fructose. In the last month, the high-fat diet was supplemented or not with CAF or a GCE, providing 5 mg/kg of CAF. Plasma lipid levels and the hepatic expression of molecules involved in lipid metabolism were determined. Lipidomic analysis was performed in liver samples. The diet caused hepatic steatosis without obesity, inflammation, endoplasmic reticulum stress, or hepatic insulin resistance. Neither CAF nor GCE alleviated hepatic steatosis, but GCE-treated rats showed lower hepatic triglyceride levels compared to the CAF group. The GCE effects could be related to reductions of hepatic (i) mTOR phosphorylation, leading to higher nuclear lipin-1 levels and limiting lipogenic gene expression; (ii) diacylglycerol levels; (iii) hexosylceramide/ceramide ratios; and (iv) very-low-density lipoprotein receptor expression. In conclusion, a low dose of CAF did not reduce hepatic steatosis in lean female rats, but the same dose provided as a green coffee extract led to lower liver triglyceride levels.

scholarly journals O-1602 Promotes Hepatic Steatosis through GPR55 and PI3 Kinase/Akt/SREBP-1c Signaling in Mice

2021 ◽  
Vol 22 (6) ◽  
pp. 3091
Author(s):  
Saeromi Kang ◽  
Ae-Yeon Lee ◽  
So-Young Park ◽  
Kwang-Hyeon Liu ◽  
Dong-Soon Im
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Pi3 Kinase ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease is recognized as the leading cause of chronic liver disease. Overnutrition and obesity are associated with hepatic steatosis. G protein-coupled receptor 55 (GPR55) has not been extensively studied in hepatic steatosis, although its endogenous ligands have been implicated in liver disease progression. Therefore, the functions of GPR55 were investigated in Hep3B human hepatoma cells and mice fed high-fat diets. O-1602, the most potent agonist of GPR55, induced lipid accumulation in hepatocytes, which was reversed by treatment with CID16020046, an antagonist of GPR55. O-1602 also induced intracellular calcium rise in Hep3B cells in a GPR55-independent manner. O-1602-induced lipid accumulation was dependent on the PI3 kinase/Akt/SREBP-1c signaling cascade. Furthermore, we found increased levels of lysophosphatidylinositol species of 16:0, 18:0, 18:1, 18:2, 20:1, and 20:2 in the livers of mice fed a high-fat diet for 4 weeks. One-week treatment with CID16020046 suppressed high-fat diet-induced lipid accumulation and O-1602-induced increase of serum triglyceride levels in vivo. Therefore, the present data suggest the pro-steatotic function of GPR55 signaling in hepatocytes and provide a potential therapeutic target for non-alcoholic fatty liver disease.

scholarly journals Prolyl Endopeptidase Gene Disruption Improves Gut Dysbiosis and Non-alcoholic Fatty Liver Disease in Mice Induced by a High-Fat Diet

2021 ◽  
Vol 9 ◽  
Author(s):  
Daixi Jiang ◽  
Jianbin Zhang ◽  
Shuangzhe Lin ◽  
Yuqin Wang ◽  
Yuanwen Chen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Neutrophil Infiltration ◽  
Prolyl Endopeptidase ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

The gut-liver axis is increasingly recognized as being involved in the pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD). Prolyl endopeptidase (PREP) plays a role in gut metabolic homeostasis and neurodegenerative diseases. We investigated the role of PREP disruption in the crosstalk between gut flora and hepatic steatosis or inflammation in mice with NAFLD. Wild-type mice (WT) and PREP gene knocked mice (PREPgt) were fed a low-fat diet (LFD) or high-fat diet (HFD) for 16 or 24 weeks. Murine gut microbiota profiles were generated at 16 or 24 weeks. Liver lipogenesis-associated molecules and their upstream mediators, AMP-activated protein kinase (AMPK) and sirtuin1 (SIRT1), were detected using RT-PCR or western blot in all mice. Inflammatory triggers and mediators from the gut or infiltrated inflammatory cells and signal mediators, such as p-ERK and p-p65, were determined. We found that PREP disruption modulated microbiota composition and altered the abundance of several beneficial bacteria such as the butyrate-producing bacteria in mice fed a HFD for 16 or 24 weeks. The level of butyrate in HFD-PREPgt mice significantly increased compared with that of the HFD-WT mice at 16 weeks. Interestingly, PREP disruption inhibited p-ERK and p-p65 and reduced the levels of proinflammatory cytokines in response to endotoxin and proline-glycine-proline, which guided macrophage/neutrophil infiltration in mice fed a HFD for 24 weeks. However, at 16 weeks, PREP disruption, other than regulating hepatic inflammation, displayed improved liver lipogenesis and AMPK/SIRT1 signaling. PREP disruption may target multiple hepatic mechanisms related to the liver, gut, and microbiota, displaying a dynamic role in hepatic steatosis and inflammation during NAFLD. PREP might serve as a therapeutic target for NAFLD.

scholarly journals Maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takuya Kawamura ◽  
Hiroaki Tanaka ◽  
Ryota Tachibana ◽  
Kento Yoshikawa ◽  
Shintaro Maki ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fetal Growth ◽  
Fetal Programming ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Control Group ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

AbstractWe aimed to investigate the effects of maternal tadalafil therapy on fetal programming of metabolic function in a mouse model of fetal growth restriction (FGR). Pregnant C57BL6 mice were divided into the control, L-NG-nitroarginine methyl ester (L-NAME), and tadalafil + L-NAME groups. Six weeks after birth, the male pups in each group were given a high-fat diet. A glucose tolerance test (GTT) was performed at 15 weeks and the pups were euthanized at 20 weeks. We then assessed the histological changes in the liver and adipose tissue, and the adipocytokine production. We found that the non-alcoholic fatty liver disease activity score was higher in the L-NAME group than in the control group (p < 0.05). Although the M1 macrophage numbers were significantly higher in the L-NAME/high-fat diet group (p < 0.001), maternal tadalafil administration prevented this change. Moreover, the epididymal adipocyte size was significantly larger in the L-NAME group than in the control group. This was also improved by maternal tadalafil administration (p < 0.05). Further, we found that resistin levels were significantly lower in the L-NAME group compared to the control group (p < 0.05). The combination of exposure to maternal L-NAME and a high-fat diet induced glucose impairment and non-alcoholic fatty liver disease. However, maternal tadalafil administration prevented these complications. Thus, deleterious fetal programming caused by FGR might be modified by in utero intervention with tadalafil.

scholarly journals Ezetimibe prevents the development of non-alcoholic fatty liver disease induced by high-fat diet in C57BL/6J mice

2014 ◽  
Vol 10 (6) ◽  
pp. 2917-2923 ◽  
Author(s):  
XIANG WANG ◽  
QIAOHUA REN ◽  
TAO WU ◽  
YONG GUO ◽  
YONG LIANG ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Triterpenoid-Rich Fraction from Ilex hainanensis Merr. Attenuates Non-Alcoholic Fatty Liver Disease Induced by High Fat Diet in Rats

2013 ◽  
Vol 41 (03) ◽  
pp. 487-502 ◽  
Author(s):  
Wei-Xi Cui ◽  
Jie Yang ◽  
Xiao-Qing Chen ◽  
Qian Mao ◽  
Xiang-Lan Wei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Liver Disease ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Density Lipoprotein ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Cyp2e1 Expression ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) has become a major challenge to the healthcare system. This study was designed to evaluate the effect of the triterpenoid-rich fraction (TF) from Ilex hainanensis Merr. on NAFLD. Male Sprague-Dawley (SD) rats were fed a normal diet (control) or high fat diet (NAFLD model). After four weeks, the high fat diet group was orally administrated TF (250 mg/kg) for another two weeks. High fat diet fed rats displayed hyperlipidemia and a decline in liver function compared with control. However, administration with TF could effectively improve these symptoms, as demonstrated by decreasing the plasma levels of triglyceride (p <0.05), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p < 0.05), alanine transaminase (p < 0.05), aspartate aminotransferase (p < 0.01), liver index (p < 0.05) and insulin resistance index (p < 0.05) while increasing the high-density lipoprotein cholesterol (p < 0.05). Meanwhile, histopathological examination of livers also showed that TF could reduce the incidence of liver lesions induced by high fat diet. Furthermore, TF could alleviate oxidative stress and inflammation status indicated by the decline malondialdehyde and superoxide dismutase levels (p < 0.01, both) and levels of interleukin 6 and tumor necrosis factor-α (p < 0.05). In addition, immunohistochemistry showed TF evidently elevated the peroxisome proliferator-activated receptor (PPARα) expression (p < 0.01), while it diminished the Cytochrome P450 2E1 (CYP2E1) expression (p < 0.01) in liver. These results demonstrate that TF has potential ability to protect liver against NAFLD by regulating lipids metabolism and alleviating insulin resistance, inflammation and oxidative stress. This effect might be associated with regulating PPARα and CYP2E1 expression.

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