Adipose differentiation related protein induces lipid accumulation and lipid droplet formation in hepatic stellate cells

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.

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Storage of retinyl esters in hepatic stellate cells: The role of LRAT in stellate cell lipid droplet formation

The FASEB Journal ◽

10.1096/fasebj.22.1_supplement.451.5 ◽

2008 ◽

Vol 22 (S1) ◽

Author(s):

Sheila M O'Byrne ◽

Jenny Libien ◽

Johannes Kluwe ◽

Robert Schwabe ◽

Krzysztof Plczewski ◽

...

Keyword(s):

Lipid Droplet ◽

Hepatic Stellate Cells ◽

Stellate Cell ◽

Stellate Cells ◽

Droplet Formation ◽

Cell Lipid ◽

Lipid Droplet Formation ◽

Retinyl Esters

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Thiazolidinedione-induced lipid droplet formation during osteogenic differentiation

Journal of Endocrinology ◽

10.1530/joe-14-0425 ◽

2014 ◽

Vol 223 (2) ◽

pp. 119-132 ◽

Cited By ~ 9

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.

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Abstract 471: Triglyceride-rich Lipoprotein Lipolysis Products Induce Adipose Differentiation Related Protein Expression and Proatherogenic Cytokine Secretion in Monocytes

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.33.suppl_1.a471 ◽

2013 ◽

Vol 33 (suppl_1) ◽

Author(s):

Jennifer E Norman ◽

Hnin H Aung ◽

John C Rutledge

Keyword(s):

Cardiovascular Disease ◽

Protein Expression ◽

Lipid Droplet ◽

Control Treatment ◽

Atherosclerotic Cardiovascular Disease ◽

Elevated Blood ◽

Related Protein ◽

Lipid Droplet Formation ◽

Increased Risk ◽

Adipose Differentiation

Elevated blood triglyceride levels are associated with an increased risk of atherosclerotic cardiovascular disease. Blood triglycerides are contained within very low density lipoproteins (VLDL) and chylomicrons, which are referred to as triglyceride-rich lipoproteins (TGRL). The enzyme lipoprotein lipase is responsible for the hydrolysis of these triglycerides, primarily into free fatty acids and glycerol. Our lab has shown that these lipolysis products induce lipid droplet formation in monocytes and can induce a proinflammatory state in multiple cell types. Other investigators have linked adipose differentiation related protein (ADRP, also known as perilipin 2 or adipophilin) to lipid droplet formation in monocyte-derived macrophage foam cells. The objectives of this study are to further understand the effects of TGRL lipolysis products on the formation of lipid droplets in monocytes and monocyte activation. We hypothesize that TGRL lipolysis products increase the expression of ADRP and the secretion of proatherogenic cytokines in THP-1 monocytes. In this study, we analyzed the global gene expression in THP-1 monocytes exposed to TGRL lipolysis products. ADRP was identified as a principal response lipid droplet associated gene induced by exposure to TGRL lipolysis products when compared to the control treatment. Induction of protein expression was analyzed by western blot. The TGRL lipolysis product treatment was also found to induce genes associated with atherosclerosis and monocyte adherence to endothelium including growth differentiation factor 15 (GDF15) and interleukin 8 (IL-8) when compared to the control treatment. We measured the secretion of GDF15 and IL-8 by ELISA. Our results indicate that mRNA and protein expression of ADRP and secretion of proatherogenic cytokines (GDF15 and IL-8) were increased in monocytes after exposure to TGRL lipolysis products. In conclusion, our study demonstrates that TGRL lipolysis products induce the expression of ADRP and the secretion of proatherogenic cytokines in monocytes. These results may indicate a role for TGRL lipolysis products in the increased risk of atherosclerotic cardiovascular disease for individuals with elevated blood triglyceride levels.

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