LSDP5 is a PAT protein specifically expressed in fatty acid oxidizing tissues

Dalen, Knut Tomas; Dahl, Tuva B.; Holter, Elin; Arntsen, Borghild; Londos, Constantine; Sztalryd, Carole; Nebb, Hilde I.

doi:10.1016/j.bbalip.2006.11.011

Cited by 213 publications

(266 citation statements)

References 68 publications

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“…Moreover, recent evidence from cell culture models suggests that perilipins 2 and 5 play roles in control of lipolysis in nonadipose tissues (15)(16)(17). Perilipin 5 is expressed in oxidative tissues where its expression is regulated by fasting and PPAR␣ (17)(18)(19). Our previous work and that of others have shown that perilipin 5 plays an important role in regulating LD accumulation (17)(18)(19)).…”

Section: Hydrolysis Of Triacylglycerol (Tag)mentioning

confidence: 99%

“…Perilipin 5 is expressed in oxidative tissues where its expression is regulated by fasting and PPAR␣ (17)(18)(19). Our previous work and that of others have shown that perilipin 5 plays an important role in regulating LD accumulation (17)(18)(19)). …”

Section: Hydrolysis Of Triacylglycerol (Tag)mentioning

confidence: 99%

“…The importance of perilipin 1 in the regulation of adipose tissue lipolysis has been well established. Moreover, recent evidence from cell culture models suggests that perilipins 2 and 5 play roles in control of lipolysis in nonadipose tissues (15)(16)(17). Perilipin 5 is expressed in oxidative tissues where its expression is regulated by fasting and PPAR␣ (17)(18)(19).…”

Section: Hydrolysis Of Triacylglycerol (Tag)mentioning

confidence: 99%

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Unique Regulation of Adipose Triglyceride Lipase (ATGL) by Perilipin 5, a Lipid Droplet-associated Protein

Wang

Bell

Sreenevasan

et al. 2011

Journal of Biological Chemistry

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226

202

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Lipolysis is a critical metabolic pathway contributing to energy homeostasis through degradation of triacylglycerides stored in lipid droplets (LDs), releasing fatty acids. Neutral lipid lipases act at the oil/water interface. In mammalian cells, LD surfaces are coated with one or more members of the perilipin protein family, which serve important functions in regulating lipolysis. We investigated mechanisms by which three perilipin proteins control lipolysis by adipocyte triglyceride lipase (ATGL), a key lipase in adipocytes and non-adipose cells. Using a cell culture model, we examined interactions of ATGL and its co-lipase CGI-58 with perilipin 1 (perilipin A), perilipin 2 (adipose differentiation-related protein), and perilipin 5 (LSDP5) using multiple techniques as follows: anisotropy Forster resonance energy transfer, coimmunoprecipitation, [32 P]orthophosphate radiolabeling, and measurement of lipolysis. The results show that ATGL interacts with CGI-58 and perilipin 5; the latter is selectively expressed in oxidative tissues. Both proteins independently recruited ATGL to the LD surface, but with opposite effects; interaction of ATGL with CGI-58 increased lipolysis, whereas interaction of ATGL with perilipin 5 decreased lipolysis. In contrast, neither perilipin 1 nor 2 interacted directly with ATGL. Activation of protein kinase A (PKA) increased [ 32 P]orthophosphate incorporation into perilipin 5 by 2-fold, whereas neither ATGL nor CGI-58 was labeled under the incubation conditions. Cells expressing both ectopic perilipin 5 and ATGL showed a 3-fold increase in lipolysis following activation of PKA. Our studies establish perilipin 5 as a novel ATGL partner and provide evidence that the protein composition of perilipins at the LD surface regulates lipolytic activity of ATGL. Hydrolysis of triacylglycerol (TAG)3 stored in the lipid droplet (LD) compartment provides a convenient source of cellular fuel for energy production during conditions such as fasting. However, lipolysis can contribute to the build up of toxic lipid intermediates and/or oxidized lipids in pathological conditions when cellular lipid homeostasis is altered, e.g. with obesity (1). Therefore, TAG hydrolysis must be carefully controlled to meet tissue-specific requirements for energy or lipid substrates in both adipose and non-adipose tissues. A better understanding of the mechanisms by which cells control lipid mobilization is needed to design novel approaches for intervention and prevention of the pathophysiological consequences of obesity.During the past 10 years, key players in the lipolytic pathway of adipocytes were identified through the study of transgenic mouse models (2-8). Phenotypic analysis of hormone-sensitive lipase null mice suggested the existence of another lipase (7), leading to the identification of adipose triglyceride lipase (ATGL) (6, 9, 10). Characterization of ATGL null mice helped to establish the respective roles of these two lipases in the lipolytic cascade (7). Complete lipolysis requires three enzyme reactions t...

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Section: Hydrolysis Of Triacylglycerol (Tag)mentioning

confidence: 99%

Section: Hydrolysis Of Triacylglycerol (Tag)mentioning

confidence: 99%

Section: Hydrolysis Of Triacylglycerol (Tag)mentioning

confidence: 99%

See 1 more Smart Citation

Unique Regulation of Adipose Triglyceride Lipase (ATGL) by Perilipin 5, a Lipid Droplet-associated Protein

Wang

Bell

Sreenevasan

et al. 2011

Journal of Biological Chemistry

Self Cite

226

202

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“…TIP47 appears to substitute the function of ADRP at least partially, and when both ADRP and TIP47 are deficient, incorporated fatty acids are used to make phospholipids rather than TG (Sztalryd et al 2006). OXPAT/MLDP/ LSDP5 enhances lipid storage by curbing lipolysis (Dalen et al 2007) and it also increases b-oxidation by recruiting CGI-58 to LDs and thereby enhancing the ATGL activity (Granneman et al 2009). Microsomal TG content is increased or decreased by deletion or overexpression of ADRP, respectively, suggesting that ADRP promotes LD formation at the expense of microsomal storage Listenberger et al 2007).…”

Section: General Lipid Droplet Functions Storage Of Lipid Estersmentioning

confidence: 99%

Not Just Fat: The Structure and Function of the Lipid Droplet

Fujimoto

Parton²

2011

Cold Spring Harbor Perspectives in Biology

408

336

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Lipid droplets (LDs) are independent organelles that are composed of a lipid ester core and a surface phospholipid monolayer. Recent studies have revealed many new proteins, functions, and phenomena associated with LDs. In addition, a number of diseases related to LDs are beginning to be understood at the molecular level. It is now clear that LDs are not an inert store of excess lipids but are dynamically engaged in various cellular functions, some of which are not directly related to lipid metabolism. Compared to conventional membrane organelles, there are still many uncertainties concerning the molecular architecture of LDs and how each function is placed in a structural context. Recent findings and remaining questions are discussed.

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“…62,63 Anti-oxidant molecule GSH reacts with ROS or functions as a cofactor of antioxidant enzymes, resulting in the protection of functions of redox-sensitive molecules, including enzymes and transcription factors. 64 Plin5 is highly expressed in oxidative tissues 42,65 and is involved in the interaction between LDs and mitochondria. 54 Knockout of Plin5 in mice increases oxidative stress to the heart.…”

Section: Plin5 Restores Ld Formation In Hscmentioning

confidence: 99%

Perilipin 5 restores the formation of lipid droplets in activated hepatic stellate cells and inhibits their activation

Lin

Chen

2016

Laboratory Investigation

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Hepatic stellate cells (HSC) are major effectors during hepatic fibrogenesis. The activation of HSC is coupled to the loss of lipid droplets (LDs), which are specialized organelles composed of neutral lipids surrounded by perilipins. LDs have emerged as a focal point of interest in understanding the metabolic regulation of intrahepatic lipids during lipid-mediated liver fibrogenesis. Perilipin 5 (Plin5) is a newly identified LD protein in the perilipin family, which plays a key role in regulating aspects of intracellular trafficking, signaling, and cytoskeletal organization in hepatocytes. Recent work in Plin5 knockout mice suggests a role in high fat diet-induced hepatic lipotoxicity. The current report is to evaluate the impact of Plin5 on HSC activation and to elucidate the underlying mechanisms. We now show that high fat diet-induced liver fibrosis is accompanied by an approximate 75% reduction in Plin5 in HSC, and that spontaneous activation of primary HSC produces temporally coincident loss of Plin5 expression and LD depletion. As modulating lipid content in HSC is a suggested strategy for inhibition of HSC activation and treatment of hepatic fibrosis, we asked whether exogenous Plin5 expression in primary HSC would reverse the activation phenotype and promote LD formation. Recombinant lentiviral Plin5 expression in primary mouse HSC restored the formation of LDs, increased lipid content by inducing expression of pro-lipogenic genes and suppressing expression of pro-lipolytic genes, and suppressed HSC activation (~two fold reduction in expression of procollagen and α-smooth muscle actin, two unique biomarkers for activated HSC). In addition, the expression of exogenous Plin5 in HSC attenuated cellular oxidative stress by reducing cellular reactive oxygen species, elevating cellular glutathione, and inducing gene expression of glutamate-cysteine ligase. Taken together, our results indicate that expression of Plin5 plays a critical role in the formation of LDs, the elevation of lipid content in HSC, and the inhibition of the activation of HSC.

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LSDP5 is a PAT protein specifically expressed in fatty acid oxidizing tissues

Cited by 213 publications

References 68 publications

Unique Regulation of Adipose Triglyceride Lipase (ATGL) by Perilipin 5, a Lipid Droplet-associated Protein

Unique Regulation of Adipose Triglyceride Lipase (ATGL) by Perilipin 5, a Lipid Droplet-associated Protein

Not Just Fat: The Structure and Function of the Lipid Droplet

Perilipin 5 restores the formation of lipid droplets in activated hepatic stellate cells and inhibits their activation

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