scholarly journals PinX1 Depletion Improves Liver Injury in a Mouse Model of Nonalcoholic Fatty Liver Disease via Increasing Telomerase Activity and Inhibiting Apoptosis

2021 ◽  
pp. 1-14
Author(s):  
Erjiong Huang ◽  
Ke Xu ◽  
Xuemei Gu ◽  
Qihan Zhu
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Telomere Length ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Telomerase Activity ◽  
Hepatocyte Apoptosis ◽  
Nonalcoholic Fatty Liver

PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) can inhibit tumor growth by inhibiting telomerase activity. However, only few studies investigated the expression and function of PinX1 in nonalcoholic fatty liver disease (NAFLD). Thus, here we aimed to explore the roles of PinX1 in high-fat diet (HFD)-induced NAFLD in mice and in isolated hepatocytes. The mRNA expression of PinX1 and mTERT as well as telomere length were analyzed by RT-PCR. Pathological changes were detected by HE staining and oil red O staining. Triglyceride, cholesterol, alanine aminotransferase, aspartic aminotransferase, and telomerase activity were detected by ELISA. Hepatocyte apoptosis was determined by TUNEL and flow cytometry, and protein expression was analyzed by western blotting. We found that the expression of PinX1 was upregulated in the HFD group compared with the WT group. <i>PinX1</i> knockout improved HFD-induced liver injury in mice and exhibited less lipid accumulation in hepatocytes. Moreover, telomere length, telomerase activity, and mTERT expression were significantly reduced in liver tissues of HFD-induced mice and palmitic acid-induced hepatocytes, while <i>PinX1</i> knockout attenuated the effect. Furthermore, HFD-induced <i>PinX1</i><sup>−/−</sup> mice exhibited less hepatocyte apoptosis than HFD-induced WT mice. Besides, <i>PinX1</i> knockout inhibited the increase of cleaved caspase-3 and cleaved PARP expression in vivo and in vitro. Moreover, inhibition of mTERT reversed the effect of <i>PinX1</i> knockout in hepatocytes. Taken together, our findings indicate that PinX1 promotes hepatocyte apoptosis and lipid accumulation by decreasing telomere length and telomerase activity in the development of NAFLD. PinX1 might be a target for the treatment of NAFLD.

scholarly journals Rubicon inhibits autophagy and accelerates hepatocyte apoptosis and lipid accumulation in nonalcoholic fatty liver disease in mice

Hepatology ◽  
2016 ◽  
Vol 64 (6) ◽  
pp. 1994-2014 ◽  
Author(s):  
Satoshi Tanaka ◽  
Hayato Hikita ◽  
Tomohide Tatsumi ◽  
Ryotaro Sakamori ◽  
Yasutoshi Nozaki ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Hepatocyte Apoptosis ◽  
Nonalcoholic Fatty Liver

scholarly journals Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease

2012 ◽  
Vol 113 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Ciaran E. Fealy ◽  
Jacob M. Haus ◽  
Thomas P. J. Solomon ◽  
Mangesh Pagadala ◽  
Chris A. Flask ◽  
...  
Keyword(s):  
Liver Disease ◽  
Insulin Sensitivity ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Fat Oxidation ◽  
Whole Body ◽  
Hepatocyte Apoptosis ◽  
Short Term ◽  
Nonalcoholic Fatty Liver

Increased hepatocyte apoptosis is a hallmark of nonalcoholic fatty liver disease (NAFLD) and contributes to the profibrogenic state responsible for the progression to nonalcoholic steatohepatitis (NASH). Strategies aimed at reducing apoptosis may result in better outcomes for individuals with NAFLD. We therefore examined the effect of a short-term exercise program on markers of apoptosis—plasma cytokeratin 18 (CK18) fragments, alanine aminotransferase (ALT), aspartate aminotransferase (AST), soluble Fas (sFas), and sFas ligand (sFasL)—in 13 obese individuals with NAFLD [body mass index 35.2 ± 1.2 kg/m2, >5% intrahepatic lipid (IHL) assessed by 1H-MR spectroscopy]. Exercise consisted of treadmill walking for 60 min/day on 7 consecutive days at ∼85% of maximal heart rate. Additionally, subjects underwent an oral glucose tolerance test and a maximal oxygen consumption (V̇o2max) test before and after the exercise intervention. The Matsuda index was used to assess insulin sensitivity. We observed significant decreases in CK18 fragments (558.4 ± 106.8 vs. 323.4 ± 72.5 U/l, P < 0.01) and ALT (30.2 ± 5.1 vs. 24.3 ± 4.8 U/l, P < 0.05), and an increase in whole body fat oxidation (49.3 ± 6.1 vs. 69.4 ± 7.1 mg/min, P < 0.05), while decreases in circulating sFasL approached statistical significance (66.5 ± 6.0 vs. 63.0 ± 5.7 pg/ml, P = 0.06), as did the relationship between percent change in circulating CK18 fragments and ALT (r = 0.55, P = 0.05). We also observed a significant correlation between changes in fat oxidation and circulating sFasL (rho = −0.65, P < 0.05). There was no change in IHL following the intervention (18.2 ± 2.5 vs. 17.5 ± 2.1%, NS). We conclude that short-term exercise reduces a circulatory marker of hepatocyte apoptosis in obese individuals with NAFLD and propose that changes in the proapoptotic environment may be mediated through improved insulin sensitivity and increased oxidative capacity.

scholarly journals Understanding the Role of Exercise in Nonalcoholic Fatty Liver Disease: ERS-Linked Molecular Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Yong Zou ◽  
Zhengtang Qi
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Molecular Pathways ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Nonalcoholic fatty liver disease (NAFLD) is globally prevalent and characterized by abnormal lipid accumulation in the liver, frequently accompanied by insulin resistance (IR), enhanced hepatic inflammation, and apoptosis. Recent studies showed that endoplasmic reticulum stress (ERS) at the subcellular level underlies these featured pathologies in the development of NAFLD. As an effective treatment, exercise significantly reduces hepatic lipid accumulation and thus alleviates NAFLD. Confusingly, these benefits of exercise are associated with increased or decreased ERS in the liver. Further, the interaction between diet, medication, exercise types, and intensity in ERS regulation is more confusing, though most studies have confirmed the benefits of exercise. In this review, we focus on understanding the role of exercise-modulated ERS in NAFLD and ERS-linked molecular pathways. Moderate ERS is an essential signaling for hepatic lipid homeostasis. Higher ERS may lead to increased inflammation and apoptosis in the liver, while lower ERS may lead to the accumulation of misfolded proteins. Therefore, exercise acts like an igniter or extinguisher to keep ERS at an appropriate level by turning it up or down, which depends on diet, medications, exercise intensity, etc. Exercise not only enhances hepatic tolerance to ERS but also prevents the malignant development of steatosis due to excessive ERS.

T1009 Severity of Liver Injury and Cardiovascular Risk in Children with Nonalcoholic Fatty Liver Disease

2009 ◽  
Vol 136 (5) ◽  
pp. A-845
Author(s):  
Valerio Nobili ◽  
Naim Alkhouri ◽  
Anna Alisi ◽  
Melania Manco ◽  
Andrea Bartuli ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Liver Disease ◽  
Liver Injury ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver
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