scholarly journals Lack of ClC-2 Alleviates High Fat Diet-Induced Insulin Resistance and Non-Alcoholic Fatty Liver Disease

2018 ◽  
Vol 45 (6) ◽  
pp. 2187-2198 ◽  
Author(s):  
Dongxia Fu ◽  
Haibin Cui ◽  
Yunna Zhang
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. This study aims to investigate whether chloride channel 2 (ClC-2) is involved in high fat diet (HFD)-induced NAFLD and possible molecular mechanisms. Methods: ClC-2 expression was liver-specifically downregulated using adeno-associated virus in C57BL/6 mice treated with a chow diet or HFD for 12 weeks. Peripheral blood and liver tissues were collected for biochemical and pathological estimation respectively. Western blotting was applied to detect the protein expressions of lipid synthesis-related enzymes and the phosphorylated level of IRS-1, Akt and mTOR. Results: ClC-2 mRNA level was significantly increased in patients with non-alcoholic steatohepatitis, which positively correlated with the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST) and insulin. Knockdown of ClC-2 in liver attenuated HFD-induced weight gain, obesity, hepatocellular ballooning, and liver lipid accumulation and fibrosis, accompanied by reduced plasma free fatty acid (FFA), triglyceride (TG), total cholesterol (TC), ALT, AST, glucose and insulin levels and homeostasis model of insulin resistance (HOMA-IR) value. Moreover, HFD-treated mice lacking ClC-2 showed inhibited hepatic lipid accumulation via regulating lipid metabolism through decreasing sterol regulatory element binding protein (SREBP)-1c expression and its downstream targeting enzymes such as fatty acid synthase (FAS), HMG-CoA reductase (HMGCR) and acetyl-Coenzyme A carboxylase (ACCα). In addition, in vivo and in vitro results demonstrated that ClC-2 downregulation in HFD-treated mice or HepG2 cells increased the sensitivity to insulin via activation of IRS-1/Akt/mTOR signaling pathway. Conclusion: Our present study reveals a critical role of ClC-2 in regulating metabolic diseases. Mice lacking ClC-2 are associated with a remarkably beneficial metabolic phenotype, suggesting that decreasing ClC-2 may be an attractive therapeutic strategy for the treatment of NAFLD.

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 Polyphenol-rich Trapa quadrispinosa pericarp extract ameliorates high-fat diet induced non-alcoholic fatty liver disease by regulating lipid metabolism and insulin resistance in mice

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8165 ◽  
Author(s):  
Tunyu Jian ◽  
Han Lü ◽  
Xiaoqin Ding ◽  
Yuexian Wu ◽  
Yuanyuan Zuo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Protein Kinase ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Model Assessment ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

In China, Trapa quadrispinosa (also called water caltrop) has long been used as a function food and folk medicine to treat diabetes mellitus for years. In the present study, the extract of T. quadrispinosa pericarp (TQPE) which mainly contains hydrolysable tannins was prepared to investigate the potential therapeutic action in non-alcoholic fatty liver disease (NAFLD) mice induced by high fat-diet (HFD). After the administration of TQPE (15, 30 mg/kg/day) for 8 weeks, the increased weight of body and liver were significantly suppressed. TQPE also ameliorated liver lipid deposition and reduced lipids parameters of blood in mice. Moreover, TQPE attenuated oxidative stress and showed a hepatoprotective effect in mice. TQPE was also found to decrease the value of homeostatic model assessment for insulin resistance. In addition, TQPE administration increased the phosphorylation of AMP-activated protein kinase (AMPK) and Acetyl-CoA carboxylase (ACC) and inhibited sterol regulatory element-binding protein (SREBP) in the liver tissue. Meanwhile, TQPE elevated insulin receptor substrate-1 (IRs-1) and protein kinase B (Akt) phosphorylation. These results reflected that, as a nature product, TQPE is a potential agent for suppressing the process of NAFLD via regulation of the AMPK/SREBP/ACC and IRs-1/Akt pathways.

scholarly journals High-fat diet leads to key hepatic miRNAs modulation that may drive lipid accumulation in liver that preceds insulin resistance in male mice

2018 ◽  
Author(s):  
Carolina Panzarin ◽  
Adriana Souza Torsoni ◽  
Laís A. de P. Simino ◽  
Mariana C. S. Mancini ◽  
Marina F. Fontana ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Male Mice ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Prevalence Of Obesity ◽  
Alcoholic Fatty Liver Disease

High-fat diet (HFD) consumption can lead to Non-Alcoholic Fatty Liver Disease (NAFLD), which is characterized by hepatic triglycerides accumulation and is directly associated with the prevalence of obesity in worldwide. Insulin resistance underlies the genesis of both obesity and NAFLD. These mecanisms can be regulated by microRNAs, such as miR-122 and Let-7 in the liver. Therefore, the aim of the present study was to investigate a possible connection between insulin resistance, obesity, NAFLD development and alterations in miR-122 and Let-7 expression in mice fed a HFD.

Induction of non-alcoholic fatty liver disease and insulin resistance by feeding a high-fat diet in rats: does coenzyme Q monomethyl ether have a modulatory effect?

Nutrition ◽  
2009 ◽  
Vol 25 (11-12) ◽  
pp. 1157-1168 ◽  
Author(s):  
Ghada M. Safwat ◽  
Stefania Pisanò ◽  
Emanuela D'Amore ◽  
Giorgio Borioni ◽  
Mariarosaria Napolitano ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Coenzyme Q ◽  
Monomethyl Ether ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease
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