The lipid droplet coat protein perilipin 5 also localizes to muscle mitochondria

Bosma, Madeleen; Minnaard, Ronnie; Sparks, Lauren M.; Schaart, Gert; Losen, Mario; Baets, Marc H. De; Duimel, Hans; Kersten, Sander; Bickel, Perry E.; Schrauwen, Patrick; Hesselink, Matthijs K. C.

doi:10.1007/s00418-011-0888-x

Cited by 142 publications

(173 citation statements)

References 43 publications

Supporting

Mentioning

151

Contrasting

Order By: Relevance

“…Here and in another recent study ( 44 ), PLIN5 protein expression was found to be elevated in muscles of exercisetrained humans. The precise function of this protein remains unclear, but several lines of evidence point to a key role for Plin5 in governing the spatial and metabolic interactions between lipid intramuscular droplets and their surrounding mitochondrial reticulum (45)(46)(47)(48).…”

Section: Resultsmentioning

confidence: 99%

PPARγ coactivator-1α contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans

Koves

Sparks

Kovalik

et al. 2013

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

Although white adipocytes are best known as the cell type that sequesters large quantities of neutral lipid, most eukaryotic cells, including skeletal myocytes, form lipid droplets. Current interests in intramyocellular triacylglycerol (IMTG) stem largely from their infamous association with metabolic disease (reviewed in Refs. 1, 2 ). Thus, in the context of obesity and type 2 diabetes, IMTG content Abstract Intramuscular accumulation of triacylglycerol, in the form of lipid droplets (LD), has gained widespread attention as a hallmark of metabolic disease and insulin resistance. Paradoxically, LDs also amass in muscles of highly trained endurance athletes who are exquisitely insulin sensitive. Understanding the molecular mechanisms that mediate the expansion and appropriate metabolic control of LDs in the context of habitual physical activity could lead to new therapeutic opportunities. Herein, we show that acute exercise elicits robust upregulation of a broad program of genes involved in regulating LD assembly, morphology, localization, and mobilization. Prominent among these was perilipin-5, a scaffolding protein that affects the spatial and metabolic interactions between LD and their surrounding mitochondrial reticulum. Studies in transgenic mice and primary human skeletal myocytes established a key role for the exercise-responsive transcriptional coactivator PGC-1 ␣ in coordinating intramuscular LD programming with mitochondrial remodeling. Moreover, translational studies comparing physically active versus inactive humans identifi ed a remarkably strong association between expression of intramuscular LD genes and enhanced insulin action in exercisetrained subjects.These results reveal an intimate molecular connection between intramuscular LD biology and mitochondrial metabolism that could prove relevant to the etiology and treatment of insulin resistance and other disorders of lipid imbalance. Abbreviations: ATGL, adipose triglyceride lipase ; BMI, body mass index; DAG, diacylglycerol; EDL, extensor digitorum longus; EE, energy expenditure; G0S2, G0/G1 switch 2; HF, high fat; HSkMC, human skeletal myotube; IMCL, intramyocellular lipid; IMTG, intramyocellular triacylglycerol; NT, nontransgenic; LD, lipid droplet; PGC-1 ␣ , PPAR ␥ coactivator-1 ␣ ; PLIN5, perilipin family protein 5; PPAR, peroxisome proliferator-activated receptor; Rd, whole-body glucose disposal; ⌬ Rd, change in whole-body glucose disposal (insulin sensitivity); RQ, respiratory quotient; ⌬ RQ, change in respiratory quotient (metabolic fl exibility); SC, standard chow; SCD1, stearoyl-CoA desaturase 1; TA, tibialis anterior; TAG, triacylglycerol; VO 2 max, maximal oxygen consumption per kilogram of body weight as measured during maximal exercise test; Wmax, maximum watts achieved per kilogram of body weight as measured during a maximal exercise test.

show abstract

Section: Resultsmentioning

confidence: 99%

PPARγ coactivator-1α contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans

Koves

Sparks

Kovalik

et al. 2013

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…PLIN5 expression is also reported in pancreatic beta cells and hepatic stellate cells [35,36]. A unique feature with PLIN5 is that mitochondria are physically recruited to lipid droplets expressing high PLIN5 (Figure 2) [37,38]. Its expression is regulated by PPAR-alpha, and most importantly, PLIN5 plays roles in regulating cellular fat oxidation.…”

Section: Plin5mentioning

confidence: 84%

Role of Lipid Droplet Proteins in the Development of NAFLD and Hepatic Insulin Resistance

Minehira¹,

Gual²

2018

Non-Alcoholic Fatty Liver Disease - Molecular Bases, Prevention and Treatment

View full text Add to dashboard Cite

NAFLD is diagnosed, when the liver fat exceeds more than 5% of liver weight. Inside of hepatocytes, these fats are stored in cytosolic lipid droplets. The lipid droplets can be formed from a bud, vesicles of the lipid bilayer, which lines at a vicinity of the endoplasmic reticulum (ER). On the surface of droplets, there are several structural/ functional proteins such as lipid droplet proteins, lipogenic enzymes, and lipases. Interestingly, the lipid droplet proteins seem to have great impact on a development of NAFLD. Some proteins can interact with transcriptional factors such as SREBP1c and PPAR-alpha/gamma, and some proteins strongly impact a mitochondrial structure. As a result, the lipid droplet proteins highly inluence lipid handling and faty acid oxidation in hepatocytes. This chapter will elucidate our recent understanding of the role of each lipid droplet protein in faty liver formation and in hepatic insulin resistance. Existing information on genetically modiied animals as well as on human NAFLD was reviewed on Perilipin families, CIDE proteins, Seipin, and PNPLAs. Finally, the chapter will discuss how the lipid droplet proteins could potentially lead/protect from hepatic insulin resistance via abnormal accumulation of ceramides and diacylglycerols, autophagy, ER stress, and oxidative stress.

show abstract

“…LDs [141], controlling both LD-TAG-derived FA release and facilitating its delivery to mitochondria for -oxidation [141,143,144]. Together, these observations indicate that mTAG pool turnover may dictate rates of FA oxidation as the majority of FA cycles through mTAG.…”

Section: Myocardial Triacylglycerol Lipolysismentioning

confidence: 95%

The role of triacylglycerol in cardiac energy provision

Evans

Hui‐Kang

2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

View full text Add to dashboard Cite

Triacylglycerols (TAG) constitute the main energy storage resource in mammals, by virtue of their high energy density. This in turn is a function of their highly reduced state and hydrophobicity.Limited water solubility, however, imposes specific requirements for delivery and uptake mechanisms on TAG-utilising tissues, including the heart, as well as intracellular disposition. TAGs constitute potentially the major energy supply for working myocardium, both through bloodborne provision and as intracellular TAG within lipid droplets, but also provide the heart with fatty acids (FA) which the myocardium cannot itself synthesise but are required for glycerolipid derivatives with (non-energetic) functions, including membrane phospholipids and lipid signalling molecules. Furthermore they serve to buffer potentially toxic amphipathic fatty acid derivatives.Intracellular handling and disposition of TAGs and their FA and glycerolipid derivatives similarly requires dedicated mechanisms in view of their hydrophobic character. Dysregulation of utilisation can result in inadequate energy provision, accumulation of TAG and/or esterified species, and these may be responsible for significant cardiac dysfunction in a variety of disease states. This review will focus on the role of TAG in myocardial energy provision, by providing FAs from exogenous and endogenous TAG sources for mitochondrial oxidation and ATP production, and how this can change in disease and impact on cardiac function. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 3Key words:heart; triacylglycerol; very-low-density lipoprotein; VLDL; chylomicron; lipid droplet Highlights: Triacylglycerols are supplied to the myocardium within chylomicrons and VLDL  Heart assimilates triacylglycerol-rich lipoproteins by LPL and receptor-mediated routes  Exogenous triacylglycerol-derived fatty acids enter an intracellular lipid pool  Intracardiac triacylglycerol is an important source of fatty acids for oxidation  Dysregulation of triacylglycerol metabolism is associated with cardiac dysfunction

show abstract

The lipid droplet coat protein perilipin 5 also localizes to muscle mitochondria

Cited by 142 publications

References 43 publications

PPARγ coactivator-1α contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans

PPARγ coactivator-1α contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans

Role of Lipid Droplet Proteins in the Development of NAFLD and Hepatic Insulin Resistance

The role of triacylglycerol in cardiac energy provision

Contact Info

Product

Resources

About