Overexpression CPT1A reduces lipid accumulation via PPARα/CD36 axis to suppress the cell proliferation in ccRCC

2021 ◽  
Author(s):  
Hui Yang ◽  
Hongbo Zhao ◽  
Zhongkun Ren ◽  
Xiaojia Yi ◽  
Qiao Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lipid Accumulation ◽  
Ppar Alpha

scholarly journals Cell Cycle Progression Regulates Biogenesis and Cellular Localization of Lipid Droplets

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
André L. S. Cruz ◽  
Nina Carrossini ◽  
Leonardo K. Teixeira ◽  
Luis F. Ribeiro-Pinto ◽  
Patricia T. Bozza ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Lipid Accumulation ◽  
Lipid Droplets ◽  
Cell Cycle Progression ◽  
Cellular Transformation ◽  
3T3 Cells ◽  
Cycle Progression ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACTIntracellular lipid accumulation has been associated with a poor prognosis in cancer. We have previously reported the involvement of lipid droplets in cell proliferation in colon cancer cells, suggesting a role for these organelles in cancer development. In this study, we evaluate the role of lipid droplets in cell cycle regulation and cellular transformation. Cell cycle synchronization of NIH 3T3 cells revealed increased numbers and dispersed distribution of lipid droplets specifically during S phase. Also, the transformed cell lineage NIH 3T3-H-rasV12showed an accumulation of both lipid droplets and PLIN2 protein above the levels in NIH 3T3 cells.PLIN2gene overexpression, however, was not able to induce NIH 3T3 cell transformation, disproving the hypothesis thatPLIN2is an oncogene. Furthermore, positive PLIN2 staining was strongly associated with highly proliferative Ki-67-positive areas in human colon adenocarcinoma tissue samples. Taken together, these results indicate that cell cycle progression is associated with tight regulation of lipid droplets, a process that is altered in transformed cells, suggesting the existence of a mechanism that connects cell cycle progression and cell proliferation with lipid accumulation.

scholarly journals Mesenchymal Stem Cells Enhance Liver Regeneration via Improving Lipid Accumulation and Hippo Signaling

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yang Liu ◽  
Faji Yang ◽  
Jun Li ◽  
Jinglin Wang ◽  
Xun Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Liver Regeneration ◽  
Lipid Accumulation ◽  
Liver Diseases ◽  
Liver Lipid ◽  
Hippo Signaling ◽  
Mechanistic Target Of Rapamycin ◽  
New Evidence

The liver has the potential to regenerate after injury. It is a challenge to improve liver regeneration (LR) after liver resection in clinical practice. Bone morrow-derived mesenchymal stem cells (MSCs) have shown to have a role in various liver diseases. To explore the effects of MSCs on LR, we established a model of 70% partial hepatectomy (PHx). Results revealed that infusion of MSCs could improve LR through enhancing cell proliferation and cell growth during the first 2 days after PHx, and MSCs could also restore liver synthesis function. Infusion of MSCs also improved liver lipid accumulation partly via mechanistic target of rapamycin (mTOR) signaling and enhanced lipid β-oxidation support energy for LR. Rapamycin-induced inhibition of mTOR decreased liver lipid accumulation at 24 h after PHx, leading to impaired LR. And after infusion of MSCs, a proinflammatory environment formed in the liver, evidenced by increased expression of IL-6 and IL-1β, and thus the STAT3 and Hippo-YAP pathways were activated to improve cell proliferation. Our results demonstrated the function of MSCs on LR after PHx and provided new evidence for stem cell therapy of liver diseases.

scholarly journals Medium for enhancing lipid accumulation and cell proliferation of Lipomyces starkeyi.

1985 ◽  
Vol 59 (12) ◽  
pp. 1263-1266 ◽  
Author(s):  
Takafumi NAGANUMA ◽  
Yasuyuki UZUKA ◽  
Kentaro TANAKA
Keyword(s):  
Cell Proliferation ◽  
Lipid Accumulation ◽  
Lipomyces Starkeyi

scholarly journals Proteomics of lipid accumulation and DGAT inhibition in HepG2 liver carcinoma cells

2021 ◽  
Author(s):  
◽  
Bhumika Bhatt-Wessel
Keyword(s):  
Cell Proliferation ◽  
Disease Progression ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Cellular Damage ◽  
Liver Carcinoma ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Treated Sample

<p>Non-alcoholic fatty liver disease (NAFLD) is a manifestation of the metabolic syndrome in the liver. It is marked by hepatocyte accumulation of triacylglycerol (TAG) rich lipid droplets. In some patients, the disease progresses to non-alcoholic steatohepatitis (NASH), characterized by cellular damage, inflammation and fibrosis. In some cases, cirrhosis and liver failure may occur. However, the pathogenesis of NAFLD is still unclear. The present project is based on the hypothesis that hepatocytes are equipped with mechanisms that allow them to manage lipid accumulation to a certain extent. Continued or increased lipid accumulation beyond this triggers molecular mechanisms such as oxidative stress, lipid peroxidation and cell death that aggravate the condition and cause disease progression. The aim of this project is to study the effects of lipid accumulation on the cells using proteomics approach to identify proteins involved in the disease progression.  A cell culture model was used in the study. HepG2 cells, a human liver carcinoma cell line, were treated with a mixture of fatty acids (FA) to induce lipid accumulation. The lipid accumulation in HepG2 cells was measured with Oil red O assay and the effect of lipid accumulation on the proliferation of the cells was measured using an MTT cell proliferation assay. HepG2 cells treated with 1 mM FA mixture for 6 hours induced lipid accumulation 1.4 times of control with 90% of cell proliferation capacity of the control cells.  The final and the only committed step in TAG biosynthesis is catalysed by acyl-CoA diacylglycerol acyltransferase (DGAT) enzymes. To investigate if limiting lipid accumulation in HepG2 cells would prevent molecular mechanisms of pathogenesis, inhibition of DGAT by small molecule inhibitors was performed. Among the three DGAT inhibitors (A922500, PF06424439 and PF04620110) tested, PF04620110 reduced the lipid accumulation to 1.2 fold of the control cells when they were treated with 100 μM of the inhibitor in the presence of 1 mM FA mixture for 6 h.  Proteomic analyses were carried out for the control, FA-treated and inhibitor-treated cell groups to identify protein changes in the abundance. Functional analyses of the changed proteins identified suggest that lipid accumulation tends to adversely affect the functioning of the ER and the mitochondria. A complex interplay between the two organelles, possibly mediated by Ca2+ signalling may be vital in ensuring cell survival. PF04620110 was able to counter the FA induced changes in the abundance of some proteins involved in the metabolic processes but it had limited effect on the ER chaperones whose abundance in the inhibitor-treated sample was comparable to that of the FA-treated sample. These data provided important information for future discoveries of biomarkers and molecular mechanisms involved in the progression of NAFLD.</p>

scholarly journals Selenium-Binding Protein 1 (SELENBP1) Supports Hydrogen Sulfide Biosynthesis and Adipogenesis

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 361 ◽  
Author(s):  
Elisa B. Randi ◽  
Giovanna Casili ◽  
Simona Jacquemai ◽  
Csaba Szabo
Keyword(s):  
Cell Proliferation ◽  
Hydrogen Sulfide ◽  
Lipid Accumulation ◽  
Intracellular Signaling ◽  
Adipocyte Differentiation ◽  
Binding Protein ◽  
Mitochondrial Activity ◽  
Knock Down ◽  
Cellular Bioenergetics

Hydrogen sulfide (H2S), a mammalian gasotransmitter, is involved in the regulation of a variety of fundamental processes including intracellular signaling, cellular bioenergetics, cell proliferation, and cell differentiation. Cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST) are currently considered the three principal mammalian H2S-generating enzymes. However, recently, a fourth H2S-producing enzyme, selenium-binding-protein 1 (SELENBP1), has also been identified. The cellular regulatory role(s) of SELENBP1 are incompletely understood. The current study investigated whether SELENBP1 plays a role in the regulation of adipocyte differentiation in vitro. 3T3-L1 preadipocytes with or without SELENBP1 knock-down were subjected to differentiation-inducing conditions, and H2S production, cellular lipid accumulation, cell proliferation, and mitochondrial activity were quantified. Adipocyte differentiation was associated with an upregulation of H2S biosynthesis. SELENBP1 silencing decreased cellular H2S levels, suppressed the expression of the three “classical” H2S-producing enzymes (CBS, CSE, and 3-MST) and significantly suppressed adipocyte differentiation. Treatment of SELENBP1 knock-down cells with the H2S donor GYY4137 partially restored lipid accumulation, increased cellular H2S levels, and exerted a bell-shaped effect on cellular bioenergetics (enhancement at 1 and 3 mM, and inhibition at 6 mM). We conclude that SELENBP1 in adipocytes (1) contributes to H2S biosynthesis and (2) acts as an endogenous stimulator of adipocyte differentiation.

scholarly journals KRAS Affects Adipogenic Differentiation by Regulating Autophagy and MAPK Activation in 3T3-L1 and C2C12 Cells

2021 ◽  
Vol 22 (24) ◽  
pp. 13630
Author(s):  
Wenjie Yu ◽  
Cheng-Zhen Chen ◽  
Yanxia Peng ◽  
Ze Li ◽  
Yan Gao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lipid Accumulation ◽  
Adipogenic Differentiation ◽  
Mammalian Target Of Rapamycin ◽  
C2c12 Cell ◽  
Small Gtpase ◽  
C2c12 Cells ◽  
Nuclear Antigen ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Kirsten rat sarcoma 2 viral oncogene homolog (Kras) is a proto-oncogene that encodes the small GTPase transductor protein KRAS, which has previously been found to promote cytokine secretion, cell survival, and chemotaxis. However, its effects on preadipocyte differentiation and lipid accumulation are unclear. In this study, the effects of KRAS inhibition on proliferation, autophagy, and adipogenic differentiation as well as its potential mechanisms were analyzed in the 3T3-L1 and C2C12 cell lines. The results showed that KRAS was localized mainly in the nuclei of 3T3-L1 and C2C12 cells. Inhibition of KRAS altered mammalian target of rapamycin (Mtor), proliferating cell nuclear antigen (Pcna), Myc, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein beta (C/ebp-β), diacylglycerol O-acyltransferase 1 (Dgat1), and stearoyl-coenzyme A desaturase 1 (Scd1) expression, thereby reducing cell proliferation capacity while inducing autophagy, enhancing differentiation of 3T3-L1 and C2C12 cells into mature adipocytes, and increasing adipogenesis and the capacity to store lipids. Moreover, during differentiation, KRAS inhibition reduced the levels of extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), p38, and phosphatidylinositol 3 kinase (PI3K) activation. These results show that KRAS has unique regulatory effects on cell proliferation, autophagy, adipogenic differentiation, and lipid accumulation.

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