scholarly journals EHD2 regulates adipocyte function and is enriched at cell surface–associated lipid droplets in primary human adipocytes

2019 ◽  
Vol 30 (10) ◽  
pp. 1147-1159 ◽  
Author(s):  
Björn Morén ◽  
Björn Hansson ◽  
Florentina Negoita ◽  
Claes Fryklund ◽  
Richard Lundmark ◽  
...  
Keyword(s):  
Cell Surface ◽  
Lipid Droplets ◽  
Energy Homeostasis ◽  
Lipid Uptake ◽  
Human Adipocytes ◽  
Adrenergic Stimulation ◽  
Triglyceride Accumulation ◽  
Aquaporin 7 ◽  
Interfering Rna

Adipocytes play a central role in energy balance, and dysfunctional adipose tissue severely affects systemic energy homeostasis. The ATPase EH domain–containing 2 (EHD2) has previously been shown to regulate caveolae, plasma membrane-specific domains that are involved in lipid uptake and signal transduction. Here, we investigated the role of EHD2 in adipocyte function. We demonstrate that EHD2 protein expression is highly up-regulated at the onset of triglyceride accumulation during adipocyte differentiation. Small interfering RNA–mediated EHD2 silencing affected the differentiation process and impaired insulin sensitivity, lipid storage capacity, and lipolysis. Fluorescence imaging revealed localization of EHD2 to caveolae, close to cell surface–associated lipid droplets in primary human adipocytes. These lipid droplets stained positive for glycerol transporter aquaporin 7 and phosphorylated perilipin-1 following adrenergic stimulation. Further, EHD2 overexpression in human adipocytes increased the lipolytic signaling and suppressed the activity of transcription factor PPARγ. Overall, these data suggest that EHD2 plays a key role for adipocyte function.

Some Observations on the Role of the Body Wall of Acanthocephalus Ranae in Lipid Uptake

1968 ◽  
Vol 48 (1) ◽  
pp. 217-225
Author(s):  
R. A. HAMMOND
Keyword(s):  
Lipid Droplets ◽  
Body Wall ◽  
The Body ◽  
Lipid Uptake ◽  
Uptake Of Nutrients ◽  
Lipid Excretion

1. Acanthocephalus ranae has been found to take up glyceryl tri[oleate-9,10-3H] solely through the surface of the trunk. The proboscis and lemnisci play no part in the uptake of this material. The large amounts of lipid present in the latter organs may be evidence of their involvement in lipid excretion. 2. Fat-soluble dyes are taken up by the animal and accumulate in lipid droplets in the lemnisci and proboscis wall. It is suggested that such dyes do not enter the animal through the surface of the proboscis, as has been suggested previously, but through the surface of the trunk. 3. The structure of the acanthocephalan body wall is discussed in relation to the uptake of nutrients.

scholarly journals FAP-1 Association with Fas (Apo-1) Inhibits Fas Expression on the Cell Surface

2003 ◽  
Vol 23 (10) ◽  
pp. 3623-3635 ◽  
Author(s):  
Vladimir N. Ivanov ◽  
Pablo Lopez Bergami ◽  
Gabriel Maulit ◽  
Taka-Aki Sato ◽  
David Sassoon ◽  
...  
Keyword(s):  
Cell Surface ◽  
Fas Ligand ◽  
Surface Expression ◽  
Dominant Negative ◽  
Intracellular Pool ◽  
C Terminus ◽  
Interfering Rna ◽  
Insight Into ◽  
Advanced Tumors

ABSTRACT As revealed by intracellular pools of nonactive Fas (Apo-1), export of Fas to the cell surface is often impaired in human tumors, thereby inactivating Fas ligand-mediated apoptosis. Here, we demonstrate that association with Fas-associated phosphatase 1 (FAP-1) attenuates Fas export to the cell surface. Forced expression of FAP-1 reduces cell surface Fas levels and increases the intracellular pool of Fas within the cytoskeleton network. Conversely, expression of dominant-negative forms of FAP-1, or inhibition of FAP-1 expression by short interfering RNA, efficiently up-regulates surface expression of Fas. Inhibition of Fas surface expression by FAP-1 depends on its association with the C terminus of Fas. Mutation within amino acid 275 results in decreased association with FAP-1 and greater export of Fas to the cell surface in melanomas, normal fibroblasts, or Fas null cells. Identifying the role of FAP-1 in binding to, and consequently inhibition of, Fas export to the cell surface provides novel insight into the mechanism underlying the regulation of Fas trafficking, which is commonly impaired in advanced tumors with FAP-1 overexpression.

scholarly journals Catalase deficiency facilitates the shuttling of free fatty acid to brown adipose tissue through lipolysis mediated by ROS during sustained fasting

2021 ◽  
Author(s):  
Raghbendra Kumar Dutta ◽  
Joon No Lee ◽  
Yunash Maharjan ◽  
Channy Park ◽  
Seong-Kyu Choe ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Redox Homeostasis ◽  
Ros Generation ◽  
Peroxisomal Enzyme ◽  
Triglyceride Accumulation ◽  
Brown Adipose

Abstract Background Fatty acids (FA) derived from adipose tissue and liver serve as the main fuel in thermogenesis of brown adipose tissue (BAT). Catalase, a peroxisomal enzyme, plays an important role in maintaining intracellular redox homeostasis by decomposing hydrogen peroxide to either water or oxygen that oxidize and provide fuel for cellular metabolism. Although the antioxidant enzymatic activity of catalase is well known, its role in the metabolism and maintenance of energy homeostasis has not yet been revealed. The present study investigated the role of catalase in lipid metabolism and thermogenesis during nutrient deprivation in catalase-knockout (KO) mice. Results We found that hepatic triglyceride accumulation in KO mice decreased during sustained fasting due to lipolysis through reactive oxygen species (ROS) generation in adipocytes. Furthermore, the free FA released from lipolysis were shuttled to BAT through the activation of CD36 and catabolized by lipoprotein lipase in KO mice during sustained fasting. Although the exact mechanism for the activation of the FA receptor enzyme is still unclear, we found that ROS generation in adipocytes mediated the shuttling of FA to BAT. Conclusions Taken together, our findings uncover the novel role of catalase in lipid metabolism and thermogenesis in BAT, which may be useful in understanding metabolic dysfunction.

scholarly journals Insulin and β-adrenergic receptors mediate lipolytic and anti-lipolytic signalling that is not altered by type 2 diabetes in human adipocytes

2019 ◽  
Vol 476 (19) ◽  
pp. 2883-2908 ◽  
Author(s):  
Cecilia Jönsson ◽  
Ana P. Castor Batista ◽  
Preben Kjølhede ◽  
Peter Strålfors
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Energy Homeostasis ◽  
Human Adipocytes ◽  
Adrenergic Stimulation ◽  
Signalling Network ◽  
Low Concentrations ◽  
Fatty Acid Release

Abstract Control of fatty acid storage and release in adipose tissue is fundamental in energy homeostasis and the development of obesity and type 2 diabetes. We here take the whole signalling network into account to identify how insulin and β-adrenergic stimulation in concert controls lipolysis in mature subcutaneous adipocytes obtained from non-diabetic and, in parallel, type 2 diabetic women. We report that, and show how, the anti-lipolytic effect of insulin can be fully explained by protein kinase B (PKB/Akt)-dependent activation of the phosphodiesterase PDE3B. Through the same PKB-dependent pathway β-adrenergic receptor signalling, via cAMP and PI3Kα, is anti-lipolytic and inhibits its own stimulation of lipolysis by 50%. Through this pathway both insulin and β-adrenergic signalling control phosphorylation of FOXO1. The dose–response of lipolysis is bell-shaped, such that insulin is anti-lipolytic at low concentrations, but at higher concentrations of insulin lipolysis was increasingly restored due to inhibition of PDE3B. The control of lipolysis was not altered in adipocytes from diabetic individuals. However, the release of fatty acids was increased by 50% in diabetes due to reduced reesterification of lipolytically liberated fatty acids. In conclusion, our results reveal mechanisms of control by insulin and β-adrenergic stimulation — in human adipocytes — that define a network of checks and balances ensuring robust control to secure uninterrupted supply of fatty acids without reaching concentrations that put cellular integrity at risk. Moreover, our results define how selective insulin resistance leave lipolytic control by insulin unaltered in diabetes, while the fatty acid release is substantially increased.

scholarly journals Catalase deficiency facilitates the shuttling of free fatty acid to brown adipose tissue through lipolysis mediated by ROS during sustained fasting

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raghbendra Kumar Dutta ◽  
Joon No Lee ◽  
Yunash Maharjan ◽  
Channy Park ◽  
Seong-Kyu Choe ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Redox Homeostasis ◽  
Ros Generation ◽  
Peroxisomal Enzyme ◽  
Triglyceride Accumulation ◽  
Brown Adipose

Abstract Background Fatty acids (FA) derived from adipose tissue and liver serve as the main fuel in thermogenesis of brown adipose tissue (BAT). Catalase, a peroxisomal enzyme, plays an important role in maintaining intracellular redox homeostasis by decomposing hydrogen peroxide to either water or oxygen that oxidize and provide fuel for cellular metabolism. Although the antioxidant enzymatic activity of catalase is well known, its role in the metabolism and maintenance of energy homeostasis has not yet been revealed. The present study investigated the role of catalase in lipid metabolism and thermogenesis during nutrient deprivation in catalase-knockout (KO) mice. Results We found that hepatic triglyceride accumulation in KO mice decreased during sustained fasting due to lipolysis through reactive oxygen species (ROS) generation in adipocytes. Furthermore, the free FA released from lipolysis were shuttled to BAT through the activation of CD36 and catabolized by lipoprotein lipase in KO mice during sustained fasting. Although the exact mechanism for the activation of the FA receptor enzyme, CD36 in BAT is still unclear, we found that ROS generation in adipocytes mediated the shuttling of FA to BAT. Conclusions Taken together, our findings uncover the novel role of catalase in lipid metabolism and thermogenesis in BAT, which may be useful in understanding metabolic dysfunction. Graphical Abstract

scholarly journals Small Interfering RNA Profiling Reveals Key Role of Clathrin-Mediated Endocytosis and Early Endosome Formation for Infection by Respiratory Syncytial Virus

2007 ◽  
Vol 81 (14) ◽  
pp. 7786-7800 ◽  
Author(s):  
Andrey A. Kolokoltsov ◽  
Drew Deniger ◽  
Elisa H. Fleming ◽  
Norbert J. Roberts ◽  
Jon M. Karpilow ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Cell Surface ◽  
Small Interfering Rna ◽  
The Elderly ◽  
Dominant Negative ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Interfering Rna

ABSTRACT Respiratory syncytial virus (RSV) is a common cause of respiratory tract infections in infants and the elderly. Like many other pH-independent enveloped viruses, RSV is thought to enter at the cell surface, independently of common endocytic pathways. We have used a targeted small interfering RNA (siRNA) library to identify key cellular genes involved in cytoskeletal dynamics and endosome trafficking that are important for RSV infection. Surprisingly, RSV infection was potently inhibited by siRNAs targeting genes associated with clathrin-mediated endocytosis, including clathrin light chain. The important role of clathrin-mediated endocytosis was confirmed by the expression of well-characterized dominant-negative mutants of genes in this pathway and by using the clathrin endocytosis inhibitor chlorpromazine. We conclude that, while RSV may be competent to enter at the cell surface, clathrin function and endocytosis are a necessary and important part of a productive RSV infection, even though infection is strictly independent of pH. These findings raise the possibility that other pH-independent viruses may share a similar dependence on endocytosis for infection and provide a new potential avenue for treatment of infection.

scholarly journals Lipid droplets fuel SARS-CoV-2 replication and production of inflammatory mediators

2020 ◽  
Author(s):  
Suelen da Silva Gomes Dias ◽  
Vinicius Cardoso Soares ◽  
André C. Ferreira ◽  
Carolina Q. Sacramento ◽  
Natalia Fintelman-Rodrigues ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Lipid Droplets ◽  
Energy Homeostasis ◽  
Lipid Synthesis ◽  
Multiple Roles ◽  
Host Cells ◽  
Intracellular Parasites ◽  
Infected Cells

AbstractViruses are obligate intracellular parasites that make use of the host metabolic machineries to meet their biosynthetic needs, identifying the host pathways essential for the virus replication may lead to potential targets for therapeutic intervention. The mechanisms and pathways explored by SARS-CoV-2 to support its replication within host cells are not fully known. Lipid droplets (LD) are organelles with major functions in lipid metabolism and energy homeostasis, and have multiple roles in infections and inflammation. Here we described that monocytes from COVID-19 patients have an increased LD accumulation compared to SARS-CoV-2 negative donors. In vitro, SARS-CoV-2 infection modulates pathways of lipid synthesis and uptake, including CD36, SREBP-1, PPARγ and DGAT-1 in monocytes and triggered LD formation in different human cells. LDs were found in close apposition with SARS-CoV-2 proteins and double-stranded (ds)-RNA in infected cells. Pharmacological modulation of LD formation by inhibition of DGAT-1 with A922500 significantly inhibited SARS-CoV-2 replication as well as reduced production of pro-inflammatory mediators. Taken together, we demonstrate the essential role of lipid metabolic reprograming and LD formation in SARS-CoV-2 replication and pathogenesis, opening new opportunities for therapeutic strategies to COVID-19.

Role of Caveolin-3 in lipid uptake and accumulation in muscle cells

2013 ◽  
Vol 8 (S 01) ◽  
Author(s):  
E Januszewicz ◽  
M Boschmann ◽  
A Foryst-Ludwig ◽  
V Benz ◽  
M Bloch ◽  
...  
Keyword(s):  
Muscle Cells ◽  
Lipid Uptake

The Role of the Interaction between Fe(III) and Cell Surface in the Accumulation of 67Ga by Tumor Cells

1991 ◽  
Vol 30 (06) ◽  
pp. 290-293 ◽  
Author(s):  
P. Maleki ◽  
A. Martinezi ◽  
M. C. Crone-Escanye ◽  
J. Robert ◽  
L. J. Anghileri
Keyword(s):  
Cell Surface ◽  
Tumor Cells ◽  
Ionic Composition ◽  
Iron Complex ◽  
Iron Binding ◽  
Complex Time ◽  
Interaction Product ◽  
Thermodynamic Constant ◽  
Number Of Cells

The study of the interaction between complexed iron and tumor cells in the presence of 67Ga-citrate indicates that a phenomenon of iron-binding related to the thermodynamic constant of stability of the iron complex, and a hydrolysis (or anion penetration) of the interaction product determine the uptake of 67Ga. The effects of various parameters such as ionic composition of the medium, nature of the iron complex, time of incubation and number of cells are discussed.

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