scholarly journals In vitro nonalcoholic fatty liver disease model with cyclo-olefin-polymer-based microphysiological systems

2021 ◽  
pp. 100010
Author(s):  
Xiaopeng Wen ◽  
Koki Yoshimoto ◽  
Makoto Yamanaka ◽  
Shiho Terada ◽  
Ken-ichiro Kamei
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Disease Model ◽  
Nonalcoholic Fatty Liver ◽  
Microphysiological Systems

scholarly journals In vitro nonalcoholic fatty liver disease model with cyclo-olefin-polymer-based microphysiological systems

2020 ◽  
Author(s):  
Xiaopeng Wen ◽  
Makoto Yamanaka ◽  
Shiho Terada ◽  
Ken-ichiro Kamei
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
New Drugs ◽  
Diagnostic Tools ◽  
Nonalcoholic Fatty Liver ◽  
Microphysiological Systems

AbstractNonalcoholic fatty liver disease (NAFLD) is one of the common chronic liver conditions, whose treatment involves curing patients without liver transplantation. Understanding the mechanism of NAFLD initiation and progression would enable development of new diagnostic tools and drugs; however, until now, the underlying mechanisms of this condition remain largely unknown owing to the lack of experimental settings that can simplify the complicated NAFLD process in vitro. Microphysiological systems (MPSs) have long been used to recapture human pathophysiological conditions in vitro for applications in drug discovery. However, polydimethylsiloxane (PDMS) has been used in most of these MPSs as the structural material; it absorbs hydrophobic molecules, such as free fatty acids (FFAs), which are the key components that initiate NAFLD. Therefore, the current PDMS-based MPSs cannot be directly applied to in vitro NALFD modeling. In this work, we present an in vitro NAFLD model with an MPS made of cyclo-olefin polymer (COP), namely COP-MPS, to prevent absorption of FFAs. We demonstrated induction of the NAFLD-like phenotype in HepaRG hepatocyte-like cells cultured in the COP-MPS by introducing FFAs. The FFAs induced lipid accumulation in the HepaRG cells, resulting in inactivation of the apoptotic cells. We believe that the proposed COP-MPS can contribute toward investigations of NAFLD mechanisms and identification of new drugs to prevent the progression of liver disease and avoid liver transplantation.

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.

Myclobutanil worsens nonalcoholic fatty liver disease: An in vitro study of toxicity and apoptosis on HepG2 cells

2016 ◽  
Vol 262 ◽  
pp. 100-104 ◽  
Author(s):  
Antonietta Stellavato ◽  
Monica Lamberti ◽  
Anna Virginia Adriana Pirozzi ◽  
Francesca de Novellis ◽  
Chiara Schiraldi
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
In Vitro Study ◽  
Vitro Study ◽  
Nonalcoholic Fatty Liver

scholarly journals Euterpe edulisExtract but Not Oil Enhances Antioxidant Defenses and Protects against Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Rodrigo Barros Freitas ◽  
Rômulo Dias Novaes ◽  
Reggiani Vilela Gonçalves ◽  
Bianca Gazolla Mendonça ◽  
Eliziária Cardoso Santos ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Antioxidant Defenses ◽  
Standard Diet ◽  
High Fat ◽  
Nonalcoholic Fatty Liver

We investigated the effects ofE. edulisbioproducts (lyophilized pulp [LEE], defatted lyophilized pulp [LDEE], and oil [EO]) on nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in rats. All products were chemically analyzed.In vivo, 42 rats were equally randomized into seven groups receiving standard diet, HFD alone or combined with EO, LEE, or LDEE. After NAFLD induction, LEE, LDEE, or EO was added to the animals’ diet for 4 weeks. LEE was rich in polyunsaturated fatty acids. From LEE degreasing, LDEE presented higher levels of anthocyanins and antioxidant capacityin vitro. Dietary intake of LEE and especially LDEE, but not EO, attenuated diet-induced NAFLD, reducing inflammatory infiltrate, steatosis, and lipid peroxidation in liver tissue. Although bothE. edulisbioproducts were not hepatotoxic, only LDEE presented sufficient benefits to treat NAFLD in rats, possibly by its low lipid content and high amount of phenols and anthocyanins.

scholarly journals Therapeutic Targeting of Nonalcoholic Fatty Liver Disease by Downregulating SREBP-1C Expression via AMPK-KLF10 Axis

2021 ◽  
Vol 8 ◽  
Author(s):  
Yu-Chi Chen ◽  
Rong-Jane Chen ◽  
Szu-Yuan Peng ◽  
Winston C. Y. Yu ◽  
Vincent Hung-Shu Chang
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Target Genes ◽  
Regulatory Element ◽  
Wild Type ◽  
Nonalcoholic Fatty Liver

Krüppel-like factor 10 (KLF10) is a phospho-regulated transcriptional factor involved in many biological processes including lipogenesis; however, the transcriptional regulation on lipogenesis by KLF10 remains largely unclear. Lipogenesis is important in the development of nonalcoholic fatty liver disease (NAFLD) which was known regulated mainly by AMP-activated protein kinase (AMPK) and sterol regulatory element-binding protein (SREBP-1C). Interesting, our previous study using phosphorylated site prediction suggested a regulation of AMPK on KLF10. Therefore, we aimed to study the protein–protein interactions of AMPK on the regulation of KLF10, and to delineate the mechanisms of phosphorylated KLF10 in the regulation of NAFLD through SREBP-1C. We performed in vitro and in vivo assays that identified AMPK phosphorylates KLF10 at Thr189 and subsequently modulates the steady state level of KLF10. Meanwhile, a chromatin immunoprecipitation–chip assay revealed the novel target genes and signaling cascades of corresponding to phosphorylated KLF10. SREBP-1C was identified as a target gene suppressed by phosphorylated KLF10 through promoter binding. We further performed high-fat-diet-induced NAFLD models using hepatic-specific KLF10 knockout mice and wild-type mice and revealed that KLF10 knockout markedly led to more severe NAFLD than that in wild-type mice. Taken together, our findings revealed for the first time that AMPK activates and stabilizes the KLF10 protein via phosphorylation at Thr189, thereby repressing the expression of SREBP-1C and subsequent lipogenesis pathways along with metabolic disorders. We suggested that the targeted manipulation of liver metabolism, particularly through increased KLF10 expression, is a potential alternative solution for treating NAFLD.

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