Role of lipid droplet proteins in liver steatosis

Okumura, Toshikatsu

doi:10.1007/s13105-011-0110-6

Cited by 90 publications

(67 citation statements)

References 64 publications

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“…The following primer sequences were used for RT-PCR: ␤ -actin forward, 5 ′ -AGC CAT GTA CGT AGC CAT CCA-3 ′ , reverse, 5 ′ -TCT CCG GAG TCC ATC ACA ATG-3 ′ ; murine Plin5 forward, 5 ′ -AGG GGA CTA GAC AAA TTG G-3 ′ , reverse, 5 ′ -GCT TCT CCG ACT TGC C-3 ′ ; Cpt1b (carnitine palmitoyltransferase 1 ␤ ) forward, 5 ′ -GGC ACC TCT TCT GCC TTT AC-3 ′ , reverse, 5 ′ -TTT GGG TCA AAC ATG CAG AT-3 ′ ; Ppara (peroxisome proliferator-activated receptor ␣ ) forward, 5 ′ -GTA CCA CTA CGG AGT TCA CGC AT-3 ′ , reverse, 5 ′ -CGC CGA AAG AAG CCC TTA C-3 ′ ; Acox1 (acylCoA oxidase 1) forward, 5 ′ -AGA TTG GTA GAA ATT GCT GCA AAA-3 ′ , reverse, 5 ′ -ACG CCA CTT CCT TGC TCT TC-3 ′ ; Acadm (acyl-CoA dehydrogenase, medium chain) forward, 5 ′ -GAT GCA TCA CCC TCG TGT AAC-3 ′ , reverse, 5 ′ -AAG CCC TTT TCC CCT GAA-3 ′ ; Acadl (acyl-CoA dehydrogenase, long chain) forward, TG mobilization from white and brown adipose tissue is a relatively well characterized process involving perilipin 1 (Plin1), adipose triglyceride lipase (ATGL), and hormonesensitive lipase (HSL) among many other proteins and cofactors ( 11,12 ). In contrast, much less is known about LD TG catabolism in nonadipose tissues, including muscle and liver, in which Plin1 is replaced by other PAT family members ( 7,13 ). More recently, perilipin 5 (Plin5) was found to be highly present on LDs of oxidative tissues including cardiac, skeletal muscle, and liver ( 14,15 ).…”

Section: Quantitative Analysis Of Mrna Expression Levelsmentioning

confidence: 99%

Cardiac-specific overexpression of perilipin 5 provokes severe cardiac steatosis via the formation of a lipolytic barrier

Pollak

Schweiger

Jaeger

et al. 2013

Journal of Lipid Research

105

104

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The ability to deposit triacylglycerol (TG) within specifi c cellular organelles is an evolutionary conserved process present in virtually every mammalian cell and in most microorganisms ( 1-3 ). TG storage within lipid droplets (LDs) not only represents an energy reservoir, but is also an important source for the generation of membrane and signaling lipids ( 4 ). However, excessive accumulation of lipids is a hallmark of many metabolic disorders including obesity, hepatic steatosis, and cardiac steatosis ( 5-7 ). Apart from that, fatty acid (FA) esterifi cation and deposition within neutral lipids protect cells from the harmful excess of nonesterifi ed FAs also referred to as lipotoxicity ( 8,9 ). The LD surface is characterized by the presence of various hydrophobic proteins including members of the so-called PAT family ( 1, 10 ) (designation derived from perilipin, adipophilin, and tail-interacting protein of 47 kDa ) and neutral lipid hydrolases, which are involved in TG breakdown and the release of FAs and glycerol.

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Section: Quantitative Analysis Of Mrna Expression Levelsmentioning

confidence: 99%

Cardiac-specific overexpression of perilipin 5 provokes severe cardiac steatosis via the formation of a lipolytic barrier

Pollak

Schweiger

Jaeger

et al. 2013

Journal of Lipid Research

105

104

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“…Perilipin1/2/3/4/5 (Plin1/2/3/4/5) are LD-associated proteins in mammalian cells (15). The expression levels of Plin2, Plin3, and Plin5 are up-regulated in fatty livers (16). CIDE proteins, including Cidea, Cideb, and Cidec (also called Fsp27), are novel LD-associated proteins (17,18).…”

mentioning

confidence: 99%

Differential Roles of Cell Death-inducing DNA Fragmentation Factor-α-like Effector (CIDE) Proteins in Promoting Lipid Droplet Fusion and Growth in Subpopulations of Hepatocytes

et al. 2016

Journal of Biological Chemistry

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“…3 Perilipin 5 (Plin5) (ie, myocardial LD protein) is a newly discovered member in the Plin family. 4,5 Plin5 is mainly expressed in highly oxidative tissues, such as heart, skeletal muscle, and liver. 4,5 Recent work in Plin5 knockout mice suggests a role in high fat diet (HFD)-induced hepatic lipotoxicity.…”

mentioning

confidence: 99%

“…4,5 Plin5 is mainly expressed in highly oxidative tissues, such as heart, skeletal muscle, and liver. 4,5 Recent work in Plin5 knockout mice suggests a role in high fat diet (HFD)-induced hepatic lipotoxicity. 6 Hepatic fibrosis refers to the deposition of high-density extracellular matrix (ECM) protein forming scarring tissue due to an imbalance between fibrogenesis and fibrolysis.…”

mentioning

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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Role of lipid droplet proteins in liver steatosis

Cited by 90 publications

References 64 publications

Cardiac-specific overexpression of perilipin 5 provokes severe cardiac steatosis via the formation of a lipolytic barrier

Cardiac-specific overexpression of perilipin 5 provokes severe cardiac steatosis via the formation of a lipolytic barrier

Differential Roles of Cell Death-inducing DNA Fragmentation Factor-α-like Effector (CIDE) Proteins in Promoting Lipid Droplet Fusion and Growth in Subpopulations of Hepatocytes

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

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