Abstract 558: PCPE2 Promotes Adipocyte Maturation via Regulation of SR-BI Activity

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Hao Xu ◽  
Sushma Kaul ◽  
Elisa Maruko ◽  
Kaniz Fatema ◽  
Craig A Glastonbury ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Droplet ◽  
Critical Role ◽  
Hdl Cholesterol ◽  
Droplet Formation ◽  
Wild Type Cell ◽  
Wild Type ◽  
Mature Adipocyte ◽  
Cellular Mechanisms ◽  
Lipid Droplet Formation

Procollagen C-endopeptidase enhancer protein 2 (PCPE2) is an enhancer protein that enhances the cleavage of the C-termini of procollagen by bone morphogenetic protein 1. But the function of PCPE2 is not limited to collagen maturation. Recently our lab reported that PCPE2 increased HDL-associated cholesteryl ester uptake via scavenger receptor class B type 1 (SR-BI), an HDL cholesterol receptor highly expressed in adipose tissue. Interestingly, TwinsUK study in human provided data showing that PCPE2 mRNA is highly correlated with adipose tissue distribution. Further, our lab observed a reduced size of visceral fat pad in PCPE2 deficient mice despite its indifference in body weight compared to the wild type. To study the molecular and cellular mechanisms of how PCPE2 regulates SR-BI function and how it affects adipose tissue formation, we generated PCPE2 knockout (PCPE2 -/- ) cell line from murine preadipocyte 3T3-L1 cell using CRISPR-Cas9 technology. Induction of 3T3-L1 cell to differentiate into mature adipocyte increases the expression of both PCPE2 and SR-BI hand in hand around 3 fold, which parallels the process of lipid droplet formation. Immunofluorescence studies showed that PCPE2 is distributed all over the cell in mature adipocyte, while SR-BI is mostly distributed along the cytoplasmic and lipid droplet membranes, in addition to the perinuclear region. More interestingly, PCPE2 -/- 3T3-L1 cell shows an impairment in lipid droplet formation during the induction of differentiation, with less than 10% of cells generating lipid droplets, and the size of lipid droplet being only about 50% of that in wild type. Although PCPE2 -/- 3T3-L1 cell expresses SR-BI at a higher level compared with wild type cell, nearly 50% of the SR-BI in wild type cell are in homodimer structure while PCPE2 -/- 3T3-L1 cell has almost none SR-BI multimer, indicating that SR-BI in PCPE2 -/- 3T3-L1 cell is inactive. Taken together, we concluded that PCPE2 plays a critical role in keeping SR-BI in active conformation, which, in turn, controls adipocyte maturation. Whether this effect is associated with collagen maturation will be assessed in our future studies.

scholarly journals Thiazolidinedione-induced lipid droplet formation during osteogenic differentiation

2014 ◽  
Vol 223 (2) ◽  
pp. 119-132 ◽  
Author(s):  
M van de Vyver ◽  
E Andrag ◽  
I L Cockburn ◽  
W F Ferris
Keyword(s):  
Adipose Tissue ◽  
Lipid Droplet ◽  
Lipid Accumulation ◽  
Adipogenic Differentiation ◽  
Chronic Administration ◽  
Droplet Formation ◽  
Pcr Analysis ◽  
Mineral Density ◽  
Lipid Droplet Formation

Chronic administration of the insulin-sensitising drugs, thiazolidinediones (TZDs), results in low bone mineral density and ‘fatty bones’. This is thought to be due, at least in part, to aberrant differentiation of progenitor mesenchymal stem cells (MSCs) away from osteogenesis towards adipogenesis. This study directly compared the effects of rosiglitazone, pioglitazone, and netoglitazone treatment on osteogenesis and adipogenesis in MSCs derived from subcutaneous (SC) or visceral (PV) white adipose tissue. MSCs were isolated from adipose tissue depots of male Wistar rats and characterised using flow cytometry. The effects of TZD treatment on osteogenic and adipogenic differentiation were assessed histologically (day 14) and by quantitative PCR analysis (Pparγ2(Pparg2),Ap2(Fabp4), Adipsin(Adps),Msx2, Collagen I(Col1a1), andAlp) on days 0, 7, and 10. Uniquely, lipid droplet formation and mineralisation were found to occur concurrently in response to TZD treatment during osteogenesis. Compared with SC MSCs, PV MSCs were more prone to lipid accumulation under controlled osteogenic and adipogenic differentiation conditions. This study demonstrated that the extent of lipid accumulation is dependent on the nature of thePparligand and that SC and PV MSCs respond differently toin vitroTZD treatment, suggesting that metabolic status can contribute to the adverse effects associated with TZD treatment.

Single cell study of adipose tissue mediated lipid droplet formation and biochemical alterations in breast cancer cells

The Analyst ◽  
2019 ◽  
Vol 144 (18) ◽  
pp. 5558-5570 ◽  
Author(s):  
Christina Blücher ◽  
Carolin Zilberfain ◽  
Tom Venus ◽  
Nick Spindler ◽  
Arne Dietrich ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Cancer Cells ◽  
Lipid Droplet ◽  
Breast Cancer Cells ◽  
Neutral Lipids ◽  
Droplet Formation ◽  
Biochemical Alterations ◽  
Lipid Droplet Formation ◽  
Staining Methods

Combined staining methods for neutral lipids and confocal Raman microspectroscopy detect increased lipid droplet formation in breast cancer cells influenced by adipose tissue.

The Important Roles of Matrix Metalloproteinases in the Pathophysiology of Obesity

2017 ◽  
Vol 68 (7) ◽  
pp. 1481-1484 ◽  
Author(s):  
Radu Mihail Mirica ◽  
Mihai Ionescu ◽  
Alexandra Mirica ◽  
Octav Ginghina ◽  
Razvan Iosifescu ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Matrix Metalloproteinases ◽  
English Language ◽  
Critical Role ◽  
Animal Experiments ◽  
Hdl Cholesterol ◽  
Tissue Growth ◽  
Basement Membranes ◽  
Body Weight Reduction

Obesity involves the growth of adipose tissue cells (adipocytes and preadipocytes), as well as microvascular endothelial cells. Matrix metalloproteinases (MMPs) are relevant ezymes for the modulation of extracellular matrix (ECM) and adipocyte and preadipocytes differentiation. They are elevated in obese patients, generating abnormal ECM metabolism.[1]. This article proposes a thorough study of literature with focus on the important roles of matrix metalloproteinases in the pathophysiology of obesity. The article represents a narrative review based on an English-language PubMed research of the medical literature regardind important aspects of the proposed aim. MMP-2 activity was signi�cantly higher than MMP-9, both activities were detectable. MMP-9 was strongly correlated with body weight parameters before surgery, as well as after significant body weight reduction as a result of bariatric surgery. Concerning MMP-2 and MMP-9 they are also involved in the turnover of basement membranes both those of adipose tissue and endothelial. MMP-9 levels were moderately correlated with HDL cholesterol levels. Taken together, the present data suggest that changes in ECM through MMP-mediated degradation might play a critical role in the adipocyte differentiation process. These findings are detected both in clinical trials and in laboratory animal experiments. It is then tempting to speculate that the adipocyte-derived MMPs might represent a new pharmacological target for the inhibition of adipose tissue growth by inhibiting adipose differentiation as well as angiogenic process.

ChemInform Abstract: Beauveriolides, Specific Inhibitors of Lipid Droplet Formation in Mouse Macrophages, Produced by Beauveria sp. FO-6979.

ChemInform ◽  
2010 ◽  
Vol 30 (27) ◽  
pp. no-no
Author(s):  
Ichiji Namatame ◽  
Hiroshi Tomoda ◽  
Shuyi Si ◽  
Yuichi Yamaguchi ◽  
Rokuro Masuma ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Droplet Formation ◽  
Lipid Droplet Formation ◽  
Mouse Macrophages ◽  
Specific Inhibitors

P0952 : Transient hepatic overexpression of the insuline-like growth factor 2 (IGF2) induces lipid droplet formation

2015 ◽  
Vol 62 ◽  
pp. S702-S703 ◽  
Author(s):  
S.M. Kessler ◽  
S. Laggai ◽  
E. Van Wonterghem ◽  
R.E. Vandenbroucke ◽  
M. Ogris ◽  
...  
Keyword(s):  
Growth Factor ◽  
Lipid Droplet ◽  
Droplet Formation ◽  
Lipid Droplet Formation

scholarly journals MicroRNA-122 Inhibits Lipid Droplet Formation and Hepatic Triglyceride Accumulation via Yin Yang 1

2017 ◽  
Vol 44 (4) ◽  
pp. 1651-1664 ◽  
Author(s):  
Guo-yi Wu ◽  
Chen Rui ◽  
Ji-qiao Chen ◽  
Eiketsu Sho ◽  
Shan-shan Zhan ◽  
...  
Keyword(s):  
Quantitative Pcr ◽  
Lipid Droplet ◽  
Droplet Formation ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Hepatic Triglyceride ◽  
Yin Yang 1 ◽  
Lipid Droplet Formation ◽  
Huh7 Cells ◽  
Yin Yang

Background/Aims: An increase in intracellular lipid droplet formation and hepatic triglyceride (TG) content usually results in nonalcoholic fatty liver disease. However, the mechanisms underlying the regulation of hepatic TG homeostasis remain unclear. Methods: Oil red O staining and TG measurement were performed to determine the lipid content. miRNA expression was evaluated by quantitative PCR. A luciferase assay was performed to validate the regulation of Yin Yang 1 (YY1) by microRNA (miR)-122. The effects of miR-122 expression on YY1 and its mechanisms involving the farnesoid X receptor and small heterodimer partner (FXR-SHP) pathway were evaluated by quantitative PCR and Western blot analyses. Results: miR-122 was downregulated in free fatty acid (FFA)-induced steatotic hepatocytes, and streptozotocin and high-fat diet (STZ-HFD) induced nonalcoholic steatohepatitis (NASH) in mice. Transfection of hepatocytes with miR-122 mimics before FFA induction inhibited lipid droplet formation and TG accumulation in vitro. These results were verified by overexpressing miR-122 in the livers of STZ-HFD-induced NASH mice. The 3’-untranslated region (3’UTR) of YY1 mRNA is predicted to contain an evolutionarily conserved miR-122 binding site. In silico searches, a luciferase reporter assay and quantitative PCR analysis confirmed that miR-122 directly bound to the YY1 3’UTR to negatively regulate YY1 mRNA in HepG2 and Huh7 cells. The (FXR-SHP) signaling axis, which is downstream of YY1, may play a key role in the mechanism of miR-122-regulated lipid homeostasis. YY1-FXR-SHP signaling, which is negatively regulated by FFA, was enhanced by miR-122 overexpression. This finding was also confirmed by overexpression of miR-122 in the livers of NASH mice. Conclusions: The present results indicate that miR-122 plays an important role in lipid (particularly TG) accumulation in the liver by reducing YY1 mRNA stability to upregulate FXR-SHP signaling.

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