scholarly journals Skeletal muscle PLIN proteins, ATGL and CGI-58, interactions at rest and following stimulated contraction

2013 ◽  
Vol 304 (8) ◽  
pp. R644-R650 ◽  
Author(s):  
Rebecca E. K. MacPherson ◽  
Sofhia V. Ramos ◽  
Rene Vandenboom ◽  
Brian D. Roy ◽  
Sandra J. Peters
Keyword(s):  
Skeletal Muscle ◽  
Lipid Droplet ◽  
Protein Interactions ◽  
Droplet Surface ◽  
Gene Identification ◽  
Protein Protein Interactions ◽  
Muscle Lipid ◽  
Associated Proteins ◽  
Skeletal Muscle Lipid ◽  
Intramuscular Lipid

Evidence indicates that skeletal muscle lipid droplet-associated proteins (PLINs) regulate lipolysis through protein-protein interactions on the lipid droplet surface. In adipocytes, PLIN1 is thought to regulate lipolysis by directly interacting with comparative gene identification-58 (CGI-58), an activator of adipose triglyceride lipase (ATGL). Upon lipolytic stimulation, PLIN1 is phosphorylated, releasing CGI-58 to fully activate ATGL and initiate triglyceride breakdown. The absence of PLIN1 in skeletal muscle leads us to believe that other PLIN family members undertake this role. Our purpose was to examine interactions between PLIN2, PLIN3, and PLIN5, with ATGL and its coactivator CGI-58 at rest and following contraction. Isolated rat solei were incubated for 30 min at rest or during 30 min of intermittent tetanic stimulation [150-ms volleys at 60 Hz with a train rate of 20 tetani/min (25°C)] to maximally stimulate intramuscular lipid breakdown. Results show that the interaction between ATGL and CGI-58 increased 128% following contraction ( P = 0.041). Further, ATGL interacts with PLIN2, PLIN3, and PLIN5 at rest and following contraction. The PLIN2-ATGL interaction decreased significantly by 21% following stimulation ( P = 0.013). Both PLIN3 and PLIN5 coprecipitated with CGI-58 at rest and following contraction, while there was no detectable interaction between PLIN2 and CGI-58 in either condition. Therefore, our findings indicate that in skeletal muscle, during contraction-induced muscle lipolysis, ATGL and CGI-58 strongly associate and that the PLIN proteins work together to regulate lipolysis, in part, by preventing ATGL and CGI-58 interactions at rest.

Subcellular localization of skeletal muscle lipid droplets and PLIN family proteins OXPAT and ADRP at rest and following contraction in rat soleus muscle

2012 ◽  
Vol 302 (1) ◽  
pp. R29-R36 ◽  
Author(s):  
Rebecca E. K. MacPherson ◽  
Eric A. F. Herbst ◽  
Erica J. Reynolds ◽  
Rene Vandenboom ◽  
Brian D. Roy ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lipid Droplet ◽  
Protein Interactions ◽  
Lipid Droplets ◽  
Droplet Surface ◽  
Protein Protein Interactions ◽  
Muscle Lipid ◽  
Droplet Distribution ◽  
Associated Proteins ◽  
Skeletal Muscle Lipid

Skeletal muscle lipid droplet-associated proteins (PLINs) are thought to regulate lipolysis through protein-protein interactions on the lipid droplet surface. In adipocytes, PLIN2 [adipocyte differentiation-related protein (ADRP)] is found only on lipid droplets, while PLIN5 (OXPAT, expressed only in oxidative tissues) is found both on and off the lipid droplet and may be recruited to lipid droplet membranes when needed. Our purpose was to determine whether PLIN5 is recruited to lipid droplets with contraction and to investigate the myocellular location and colocalization of lipid droplets, PLIN2, and PLIN5. Rat solei were isolated, and following a 30-min equilibration period, they were assigned to one of two groups: 1) 30 min of resting incubation and 2) 30 min of stimulation ( n = 10 each). Immunofluorescence microscopy was used to determine subcellular content, distribution, and colocalization of lipid droplets, PLIN2, and PLIN5. There was a main effect for lower lipid and PLIN2 content in stimulated compared with rested muscles ( P < 0.05). Lipid droplet distribution declined exponentially from the sarcolemma to the fiber center in the rested muscles ( P = 0.001, r2= 0.99) and linearly in stimulated muscles (slope = −0.0023 ± 0.0006, P < 0.001, r2= 0.93). PLIN2 distribution declined exponentially from the sarcolemma to the fiber center in both rested and stimulated muscles ( P < 0.0001, r2= 0.99 rest; P = 0.0004, r2= 0.98 stimulated), while PLIN5 distribution declined linearly (slope = −0.0085 ± 0.0009, P < 0.0001, r2= 0.94 rest; slope=−0.0078 ± 0.0010, P = 0.0003, r2= 0.91 stimulated). PLIN5-lipid droplets colocalized at rest with no difference poststimulation ( P = 0.47; rest r2= 0.55 ± 0.02, stimulated r2= 0.58 ± 0.03). PLIN2-lipid droplets colocalized at rest with no difference poststimulation ( P = 0.48; rest r2= 0.66 ± 0.02, stimulated r2= 0.65 ± 0.02). Contrary to our hypothesis, these results show that PLIN5 is not recruited to lipid droplets with contraction in isolated skeletal muscle.

Piecing together the puzzle of perilipin proteins and skeletal muscle lipolysis

2015 ◽  
Vol 40 (7) ◽  
pp. 641-651 ◽  
Author(s):  
Rebecca E.K. MacPherson ◽  
Sandra J. Peters
Keyword(s):  
Skeletal Muscle ◽  
Lipid Droplet ◽  
Droplet Surface ◽  
Gene Identification ◽  
Droplet Growth ◽  
Muscle Lipid ◽  
Complex Process ◽  
Skeletal Muscle Lipid ◽  
Working Together ◽  
Hydrolysis Of

The regulation of skeletal muscle lipolysis and fat oxidation is a complex process involving multiple proteins and enzymes. Emerging work indicates that skeletal muscle PLIN proteins likely play a role in the hydrolysis of triglycerides stored in lipid droplets and the passage of fatty acids to the mitochondria for oxidation. In adipocytes, PLIN1 regulates lipolysis by interacting with comparative gene identification-58 (CGI-58), an activator of adipose triglyceride lipase (ATGL). Upon lipolytic stimulation, PLIN1 is phosphorylated, releasing CGI-58 to activate ATGL and initiate triglyceride breakdown. The absence of PLIN1 in skeletal muscle leads us to believe that other PLIN family members undertake this role. The focus of this review is on the PLIN family proteins expressed in skeletal muscle: PLIN2, PLIN3, and PLIN5. To date, most studies involving these PLIN proteins have used nonmuscle tissues and cell cultures to determine their potential roles. Results from work in these models support a role for PLIN proteins in sequestering lipases during basal conditions and in potentially working together for lipase translocation and activity during lipolysis. In skeletal muscle, PLIN2 tends to mirror the lipid content and may play a role in lipid droplet growth and stability through lipase interactions on the lipid droplet surface, whereas the skeletal muscle roles of both PLIN3 and PLIN5 seem to be more complex because they are found not only on the lipid droplet, but also at the mitochondria. Clearly, further work is needed to fully understand the intricate mechanisms by which PLIN proteins contribute to skeletal muscle lipid metabolism.

Proteome of Skeletal Muscle Lipid Droplet Reveals Association with Mitochondria and Apolipoprotein A-I

2011 ◽  
Vol 10 (10) ◽  
pp. 4757-4768 ◽  
Author(s):  
Huina Zhang ◽  
Yang Wang ◽  
Jing Li ◽  
Jinhai Yu ◽  
Jing Pu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lipid Droplet ◽  
Muscle Lipid ◽  
Apolipoprotein A ◽  
Skeletal Muscle Lipid

scholarly journals Effects of Simvastatin on Lipid Metabolism in Wild-Type Mice and Mice with Muscle PGC-1α Overexpression

2021 ◽  
Vol 22 (9) ◽  
pp. 4950
Author(s):  
Miljenko V. Panajatovic ◽  
Francois Singh ◽  
Stephan Krähenbühl ◽  
Jamal Bouitbir
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Glucose Uptake ◽  
Lipid Droplet ◽  
Wild Type ◽  
Fatty Acid Binding ◽  
Muscle Lipid ◽  
Skeletal Muscle Lipid ◽  
Fatty Acid Transporter

Previous studies suggest that statins may disturb skeletal muscle lipid metabolism potentially causing lipotoxicity with insulin resistance. We investigated this possibility in wild-type mice (WT) and mice with skeletal muscle PGC-1α overexpression (PGC-1α OE mice). In WT mice, simvastatin had only minor effects on skeletal muscle lipid metabolism but reduced glucose uptake, indicating impaired insulin sensitivity. Muscle PGC-1α overexpression caused lipid droplet accumulation in skeletal muscle with increased expression of the fatty acid transporter CD36, fatty acid binding protein 4, perilipin 5 and CPT1b but without significant impairment of muscle glucose uptake. Simvastatin further increased the lipid droplet accumulation in PGC-1α OE mice and stimulated muscle glucose uptake. In conclusion, the impaired muscle glucose uptake in WT mice treated with simvastatin cannot be explained by lipotoxicity. PGC-1α OE mice are protected from lipotoxicity of fatty acids and triglycerides by increased the expression of FABP4, formation of lipid droplets and increased expression of CPT1b.

Intramyocellular fat storage in metabolic diseases

2016 ◽  
Vol 26 (1) ◽  
Author(s):  
Claire Laurens ◽  
Cedric Moro
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Metabolic Diseases ◽  
Recent Literature ◽  
Lipid Storage ◽  
Muscle Lipid ◽  
The Past ◽  
Skeletal Muscle Lipid ◽  
Ectopic Lipid Storage

AbstractOver the past decades, obesity and its metabolic co-morbidities such as type 2 diabetes (T2D) developed to reach an endemic scale. However, the mechanisms leading to the development of T2D are still poorly understood. One main predictor for T2D seems to be lipid accumulation in “non-adipose” tissues, best known as ectopic lipid storage. A growing body of data suggests that these lipids may play a role in impairing insulin action in metabolic tissues, such as liver and skeletal muscle. This review aims to discuss recent literature linking ectopic lipid storage and insulin resistance, with emphasis on lipid deposition in skeletal muscle. The link between skeletal muscle lipid content and insulin sensitivity, as well as the mechanisms of lipid-induced insulin resistance and potential therapeutic strategies to alleviate lipotoxic lipid pressure in skeletal muscle will be discussed.

scholarly journals The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men

2011 ◽  
Vol 53 (3) ◽  
pp. 577-586 ◽  
Author(s):  
Jeffrey D. Browning ◽  
Jeannie Baxter ◽  
Santhosh Satapati ◽  
Shawn C. Burgess
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Short Term ◽  
Muscle Lipid ◽  
Healthy Women ◽  
Skeletal Muscle Lipid

Leucine periodicity of U2 small nuclear ribonucleoprotein particle (snRNP) A' protein is implicated in snRNP assembly via protein-protein interactions

1991 ◽  
Vol 11 (3) ◽  
pp. 1578-1589
Author(s):  
L D Fresco ◽  
D S Harper ◽  
J D Keene
Keyword(s):  
Protein Interactions ◽  
Leucine Zipper ◽  
Tandem Repeats ◽  
Mutational Analysis ◽  
Particle Density ◽  
Protein Protein Interactions ◽  
Small Nuclear Ribonucleoprotein ◽  
Cell Extracts ◽  
Associated Proteins ◽  
Nuclear Ribonucleoprotein

Recombinant A' protein could be reconstituted into U2 small nuclear ribonucleoprotein particles (snRNPs) upon addition to HeLa cell extracts as determined by coimmunoprecipitation and particle density; however, direct binding to U2 RNA could not be demonstrated except in the presence of the U2 snRNP B" protein. Mutational analysis indicated that a central core region of A' was required for particle reconstitution. This region consists of five tandem repeats of approximately 24 amino acids each that exhibit a periodicity of leucine and asparagine residues that is distinct from the leucine zipper. Similar leucine-rich (Leu-Leu motif) repeats are characteristic of a diverse array of soluble and membrane-associated proteins from yeasts to humans but have not been reported previously to reside in nuclear proteins. Several of these proteins, including Toll, chaoptin, RNase/angiogenin inhibitors, lutropin-choriogonadotropin receptor, carboxypeptidase N, adenylyl cyclase, CD14, and human immunodeficiency virus type 1 Rev, may be involved in protein-protein interactions. Our findings suggest that in cell extracts the Leu-Leu motif of A' is required for reconstitution with U2 snRNPs and perhaps with other components involved in splicing through protein-protein interactions.

Responses of skeletal muscle lipid metabolism in rat gastrocnemius to hypothyroidism and iodothyronine administration: a putative role for FAT/CD36

2012 ◽  
Vol 303 (10) ◽  
pp. E1222-E1233 ◽  
Author(s):  
Assunta Lombardi ◽  
Rita De Matteis ◽  
Maria Moreno ◽  
Laura Napolitano ◽  
Rosa Anna Busiello ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Protein Level ◽  
Oxidation Rate ◽  
Mitochondrial Protein ◽  
Acid Oxidation ◽  
Mrna Levels ◽  
Muscle Lipid ◽  
Mitochondrial Fatty Acid ◽  
Skeletal Muscle Lipid

Iodothyronines such as triiodothyronine (T3) and 3,5-diiodothyronine (T2) influence energy expenditure and lipid metabolism. Skeletal muscle contributes significantly to energy homeostasis, and the above iodothyronines are known to act on this tissue. However, little is known about the cellular/molecular events underlying the effects of T3 and T2 on skeletal muscle lipid handling. Since FAT/CD36 is involved in the utilization of free fatty acids by skeletal muscle, specifically in their import into that tissue and presumably their oxidation at the mitochondrial level, we hypothesized that related changes in lipid handling and in FAT/CD36 expression and subcellular redistribution would occur due to hypothyroidism and to T3 or T2 administration to hypothyroid rats. In gastrocnemius muscles isolated from hypothyroid rats, FAT/CD36 was upregulated (mRNA levels and total tissue, sarcolemmal, and mitochondrial protein levels). Administration of either T3 or T2 to hypothyroid rats resulted in 1) little or no change in FAT/CD36 mRNA level, 2) a decreased total FAT/CD36 protein level, and 3) further increases in FAT/CD36 protein level in sarcolemma and mitochondria. Thus, the main effect of each iodothyronine seemed to be exerted at the level of FAT/CD36 cellular distribution. The effect of further increases in FAT/CD36 protein level in sarcolemma and mitochondria was already evident at 1 h after iodothyronine administration. Each iodothyronine increased the mitochondrial fatty acid oxidation rate. However, the mechanisms underlying their rapid effects seem to differ; T2 and T3 each induce FAT/CD36 translocation to mitochondria, but only T2 induces increases in carnitine palmitoyl transferase system activity and in the mitochondrial substrate oxidation rate.

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