ADRP stimulates lipid accumulation and lipid droplet formation in murine fibroblasts

2002 ◽  
Vol 283 (4) ◽  
pp. E775-E783 ◽  
Author(s):  
Minako Imamura ◽  
Toyoshi Inoguchi ◽  
Shoichiro Ikuyama ◽  
Susumu Taniguchi ◽  
Kunihisa Kobayashi ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Droplet ◽  
Lipid Accumulation ◽  
Lipid Droplets ◽  
Droplet Formation ◽  
Fatty Acid Binding ◽  
Lipogenic Genes ◽  
Lipid Droplet Formation ◽  
Murine Fibroblasts ◽  
Adipose Differentiation

Adipose differentiation-related protein (ADRP) is a lipid droplet-associated protein that is expressed early during adipose differentiation. The present study was undertaken to reveal the role of ADRP in adipose differentiation. In murine fibroblasts infected with green fluorescent protein (GFP)-ADRP fusion protein expression adenovirus vector, confocal microscopic analysis showed the number and size of lipid droplets apparently increased comparing with those of control cells. Overexpressed GFP-ADRP were mainly located at the surface of lipid droplets and appeared to be “ring-shaped.” Triacylglycerol content was also significantly ( P < 0.001) increased in GFP-ADRP-overexpressed cells compared with control cells. ADRP-induced lipid accumulation did not depend on adipocyte-specific gene induction, such as peroxisome proliferator-activated receptor-γ, lipoprotein lipase, or other lipogenic genes, including acyl-CoA synthetase, fatty acid-binding protein, and fatty acid transporter. In conclusion, ADRP stimulated lipid accumulation and lipid droplet formation without induction of other adipocyte-specific genes or other lipogenic genes in murine fibroblasts. The detailed molecular mechanisms of ADRP on lipid accumulation remain to be elucidated.

scholarly journals Decreased PEDF Promotes Hepatic Fatty Acid Uptake and Lipid Droplet Formation in the Pathogenesis of NAFLD

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 270
Author(s):  
Kuang-Tzu Huang ◽  
Kuang-Den Chen ◽  
Li-Wen Hsu ◽  
Chao-Pin Kung ◽  
Shu-Rong Li ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Droplet ◽  
Lipid Accumulation ◽  
Fatty Acid Uptake ◽  
Droplet Formation ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
Sequencing Analysis ◽  
Simple Steatosis ◽  
Lipid Droplet Formation

Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver diseases worldwide, ranges from simple steatosis to steatohepatitis, with the risk for progressive fibrosis or even cirrhosis. While simple steatosis is a relatively benign condition, the buildup of toxic lipid metabolites can induce chronic inflammation, ultimately triggering disease progression. Pigment epithelium-derived factor (PEDF) is a secreted, multifunctional glycoprotein with lipid metabolic activities. PEDF promotes lipolysis through binding to adipose triglyceride lipase (ATGL), a key enzyme for triglyceride breakdown. In the current study, we aimed to delineate how changes in PEDF expression affect hepatic lipid accumulation. Our data revealed that hepatic PEDF was downregulated in a mouse NAFLD model. We further showed that decreased PEDF levels in hepatocytes in vitro resulted in elevated fatty acid uptake and lipid droplet formation, with concomitant upregulation of fatty acid transport proteins CD36 and fatty acid binding protein 1 (FABP1). RNA sequencing analysis of PEDF knocked down hepatocytes revealed an alteration in gene expression profile toward lipid accumulation. Additionally, decreased PEDF promotes mobilization of fatty acids, an observation distinct from blocking ATGL activity. Taken together, our data suggest that hepatic PEDF downregulation causes molecular changes that favor triglyceride accumulation, which may further lead to NAFLD progression.

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.

Role of hepatic Annexin A6 in fatty acid-induced lipid droplet formation

2017 ◽  
Vol 358 (2) ◽  
pp. 397-410 ◽  
Author(s):  
Rose Cairns ◽  
Anna Alvarez-Guaita ◽  
Inés Martínez-Saludes ◽  
Sundeep J. Wason ◽  
Jacky Hanh ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Droplet ◽  
Droplet Formation ◽  
Lipid Droplet Formation

scholarly journals Retinoic acid receptor-related orphan receptor α reduces lipid droplets by upregulating neutral cholesterol ester hydrolase 1 in macrophages

2020 ◽  
Author(s):  
Hiroshi MATSUOKA ◽  
Riki TOKUNAGA ◽  
Miyu KATAYAMA ◽  
Yuichiro HOSODA ◽  
Kaoruko MIYA ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Lipid Droplet ◽  
Cholesterol Ester ◽  
Lipid Droplets ◽  
Retinoic Acid Receptor ◽  
Droplet Formation ◽  
Orphan Receptor ◽  
Acid Receptor ◽  
Ester Hydrolase ◽  
Lipid Droplet Formation

Abstract Background: Neutral cholesterol ester hydrolase 1 (NCEH1) catalyzes the hydrolysis of cholesterol ester (CE) in macrophages. Genetic ablation of NCEH1 promotes CE-laden macrophages and the development of atherosclerosis in mice. Dysregulation of NCEH1 levels is involved in the pathogenesis of multiple disorders including metabolic diseases and atherosclerosis; however, relatively little is known regarding the mechanisms regulating NCEH1. Retinoic acid receptor-related orphan receptor α (RORα)-deficient mice exhibit several phenotypes indicative of aberrant lipid metabolism, including dyslipidemia and increased susceptibility to atherosclerosis. Results: In this study, inhibition of lipid droplet formation by RORα positively regulated NCEH1 expression in macrophages. In mammals, the NCEH1 promoter region was found to harbor putative RORα response elements (ROREs). Electrophoretic mobility shift, chromatin immunoprecipitation, and luciferase reporter assays showed that RORα binds and responds to ROREs in human NCEH1. Moreover, NCEH1 was upregulated through RORα via a phorbol myristate acetate-dependent mechanism during macrophage differentiation from THP1 cells. siRNA-mediated knockdown of RORα significantly downregulated NCEH1 expression and accumulated lipid droplets in human hepatoma cells. In contrast, NCEH1 expression and removal of lipid droplets were induced by RORα agonist treatments and RORα overexpression in macrophages. Conclusion: These data strongly suggested that NCEH1 is a direct RORα target, defining potential new roles for RORα in the inhibition of lipid droplet formation through NCEH1.

scholarly journals Evaluation on the phagocytosis of apoptotic spermatogenic cells by Sertoli cells in vitro through detecting lipid droplet formation by Oil Red O staining

Reproduction ◽  
2006 ◽  
Vol 132 (3) ◽  
pp. 485-492 ◽  
Author(s):  
Huizhen Wang ◽  
Haikun Wang ◽  
Weipeng Xiong ◽  
Yongmei Chen ◽  
Quanhong Ma ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Sertoli Cells ◽  
Lipid Droplets ◽  
Apoptotic Cell ◽  
Practical Method ◽  
Droplet Formation ◽  
Spermatogenic Cells ◽  
Lipid Droplet Formation ◽  
Oil Red O

During spermatogenesis, more than half of the differentiating spermatogenic cells undergo apoptosis before they mature into spermatozoa. Ultrastructure studies showed that the formation of lipid droplets in Sertoli cells was associated with phagocytosis of residual bodies and apoptotic germ cells by Sertoli cells. Here, a relationship between the phagocytosis of apoptotic spermatogenic cells and lipid droplet formation in Sertoli cells was studiedin vitroby Oil Red O (ORO) staining. The results confirmed that the formation of lipid droplets was a result of phagocytosis of apoptotic spermatogenic cells in Sertoli cells. By comparing phagocytosis of apoptotic spermatogenic cells and thymocytes by Sertoli cells to that by macrophages, we demonstrated that the lipid droplets accumulation in phagocytes depended on phagocytosed apoptotic cell type, but not phagocyte type. However, the size of lipid droplets was related to the type of phagocytes. By this approach, we found that Sertoli cells at different postnatal stages of development had a similar phagocytic ability. These results suggested that the detection of lipid droplets by ORO staining was a practical method to evaluate the phagocytic functions of Sertoli cellsin vitro. This approach could also be considered as anin vitromodel to study the lipid formation, metabolism, and function in Sertoli cells.

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