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Aki Yamada, Kazue Honma, Kazuki Mochizuki, Toshinao Goda
OBJECTIVE: Fructose intake induces hepatic steatosis by activating fat synthesis. In this study, we searched for genes that showed acute induction in the livers of mice force-fed with fructose, and examined how this induction is regulated. MATERIALS/METHODS: We identified genes induced at 6h after the fructose force-feeding using a microarray and quantitative real-time RT-PCR. Histone acetylation and an acetylated histone binding protein bromodomain containing (BRD)4 binding around the fructose-inducible genes were examined using a chromatin immunoprecipitation assay...
October 2016: Metabolism: Clinical and Experimental
Tiffany L Morton, Kornelia Galior, Cody McGrath, Xin Wu, Gunes Uzer, Guniz Bas Uzer, Buer Sen, Zhihui Xie, David Tyson, Janet Rubin, Maya Styner
Muscle lipid increases with high-fat feeding and diabetes. In trained athletes, increased muscle lipid is not associated with insulin resistance, a phenomenon known as the athlete's paradox. To understand if exercise altered the phenotype of muscle lipid, female C57BL/6 mice fed CTL or high-fat diet (HFD for 6 or 18 weeks) were further divided into sedentary or exercising groups (CTL-E or HFD-E) with voluntary access to running wheels for the last 6 weeks of experiments, running 6 h/night. Diet did not affect running time or distance...
2016: Frontiers in Endocrinology
Sofhia V Ramos, Patrick C Turnbull, Rebecca E K MacPherson
Adipose tissue is classified as either white (WAT) or brown (BAT) and differs not only by anatomical location but also in function. WAT is the main source of stored energy and releases fatty acids in times of energy demand, whereas BAT plays a role in regulating non-shivering thermogenesis and oxidizes fatty acids released from the lipid droplet. The PLIN family of proteins has recently emerged as being integral in the regulation of fatty acid storage and release in adipose tissue. Previous work has demonstrated that PLIN protein content varies among adipose tissue depots, however an examination of endurance training-induced depot specific changes in PLIN protein expression has yet to be done...
April 2016: Adipocyte
Christina Drevinge, Knut T Dalen, Maria Nastase Mannila, Margareta Scharin Täng, Marcus Ståhlman, Martina Klevstig, Annika Lundqvist, Ismena Mardani, Fred Haugen, Per Fogelstrand, Martin Adiels, Jorge Asin-Cayuela, Charlotte Ekestam, Jesper R Gådin, Yun K Lee, Hilde Nebb, Sara Svedlund, Bengt R Johansson, Lillemor Mattsson Hultén, Stefano Romeo, Björn Redfors, Elmir Omerovic, Max Levin, Li-Ming Gan, Per Eriksson, Linda Andersson, Ewa Ehrenborg, Alan R Kimmel, Jan Borén, Malin C Levin
BACKGROUND: Myocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia. METHODS AND RESULTS: We generated Plin5(-/-) mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart...
September 15, 2016: International Journal of Cardiology
Ruzaidi A M Mohktar, Magda K Montgomery, Robyn M Murphy, Matthew J Watt
Cytoplasmic lipid droplets provide a reservoir for triglyceride storage and are a central hub for fatty acid trafficking in cells. The protein perilipin 5 (PLIN5) is highly expressed in oxidative tissues such as skeletal muscle and regulates lipid metabolism by coordinating the trafficking and the reversible interactions of effector proteins at the lipid droplet. PLIN5 may also regulate mitochondrial function, although this remains unsubstantiated. Hence, the aims of this study were to examine the role of PLIN5 in the regulation of skeletal muscle substrate metabolism during acute exercise and to determine whether PLIN5 is required for the metabolic adaptations and enhancement in exercise tolerance following endurance exercise training...
July 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Jianguo Lin, Anping Chen
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...
July 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Shirish Mishra, Roger Schneiter
Neutral lipids are packed into dedicated intracellular compartments termed lipid droplets (LDs). LDs are spherical structures delineated by an unusual lipid monolayer and they harbor a specific set of proteins, many of which function in lipid synthesis and lipid turnover. In mammals, LDs are covered by abundant scaffolding proteins, the perilipins (PLIN1-5). LDs in yeast are functionally similar to that of mammalian cells, but they lack the perilipins. We have previously shown that perilipins (PLIN1-3) are properly targeted to LDs when expressed in yeast and that they promote LD formation from the ER membrane enriched in neutral lipids...
November 2015: Communicative & Integrative Biology
Anne Gemmink, Madeleen Bosma, Helma J H Kuijpers, Joris Hoeks, Gert Schaart, Marc A M J van Zandvoort, Patrick Schrauwen, Matthijs K C Hesselink
AIMS/HYPOTHESIS: In contrast to insulin-resistant individuals, insulin-sensitive athletes possess high intramyocellular lipid content (IMCL), good mitochondrial function and high perilipin 5 (PLIN5) levels, suggesting a role for PLIN5 in benign IMCL storage. We hypothesised a role for PLIN5 in modulating fasting-mediated insulin resistance. METHODS: Twelve men were fasted for 60 h, before and after which muscle biopsies were taken and stained for lipid droplets (LDs), PLIN5 and laminin...
May 2016: Diabetologia
Rotonya M Carr, Rexford S Ahima
Cytosolic lipid droplets (LDs) are present in most cell types, and consist of a core comprising neutral lipids, mainly triglycerides and sterol esters, surrounded by a monolayer of phospholipids. LDs are heterogeneous in their structure, chemical composition, and tissue distribution. LDs are coated by several proteins, including perilipins and other structural proteins, lipogenic enzymes, lipases and membrane-trafficking proteins. Five proteins of the perilipin (PLIN) family (PLIN1 (perilipin), PLIN2 (adipose differentiation-related protein), PLIN3 (tail-interacting protein of 47kDa), PLIN4 (S3-12), and PLIN5 (myocardial lipid droplet protein)), are associated with LD formation...
January 15, 2016: Experimental Cell Research
Matthew A Sanders, Franck Madoux, Ljiljana Mladenovic, Huamei Zhang, Xiangqun Ye, Michelle Angrish, Emilio P Mottillo, Joseph A Caruso, Geoff Halvorsen, William R Roush, Peter Chase, Peter Hodder, James G Granneman
Fat and muscle lipolysis involves functional interactions of adipose triglyceride lipase (ATGL), α-β hydrolase domain-containing protein 5 (ABHD5), and tissue-specific perilipins 1 and 5 (PLIN1 and PLIN5). ABHD5 potently activates ATGL, but this lipase-promoting activity is suppressed when ABHD5 is bound to PLIN proteins on lipid droplets. In adipocytes, protein kinase A (PKA) phosphorylation of PLIN1 rapidly releases ABHD5 to activate ATGL, but mechanisms for rapid regulation of PLIN5-ABHD5 interaction in muscle are unknown...
November 3, 2015: Cell Metabolism
Michelle B Trevino, David Mazur-Hart, Yui Machida, Timothy King, Joseph Nadler, Elena V Galkina, Arjun Poddar, Sucharita Dutta, Yumi Imai
Perilipin 5 (PLIN5) is a lipid droplet (LD) protein highly expressed in oxidative tissues, including the fasted liver. However, its expression also increases in nonalcoholic fatty liver. To determine whether PLIN5 regulates metabolic phenotypes of hepatosteatosis under nutritional excess, liver targeted overexpression of PLIN5 was achieved using adenoviral vector (Ad-PLIN5) in male C57BL/6J mice fed high-fat diet. Mice treated with adenovirus expressing green fluorescent protein (GFP) (Ad-GFP) served as control...
October 2015: Molecular Endocrinology
Linda Krause, Bernhard Haubold, Angelika G Börsch-Haubold
Wild house mice form social hierarchies with aggressive males defending territories, in which females, young mice and submissive adult males share nests. In contrast, socially excluded males are barred from breeding groups, have numerous bite wounds and patches of thinning fur. Since their feeding times are often disrupted, we investigated whether social exclusion leads to changes in epigenetic marks of metabolic genes in liver tissue. We used chromatin immunoprecipitation and quantitative PCR to measure enrichment of two activating histone marks at 15 candidate loci...
2015: PloS One
Elena Revuelta-López, Roi Cal, Josep Julve, Anna Rull, Maria Martínez-Bujidos, Montserrat Perez-Cuellar, Jordi Ordoñez-Llanos, Lina Badimon, Jose Luis Sanchez-Quesada, Vicenta Llorente-Cortés
Plasma lipoproteins are a source of lipids for the heart, and the proportion of electronegative low density lipoprotein [LDL(-)] is elevated in cardiometabolic diseases. Perilipin 5 (Plin5) is a crucial protein for lipid droplet management in the heart. Our aim was to assess the effect of LDL(-) on intracellular lipid content and Plin5 levels in cardiomyocytes and to determine whether these effects were influenced by hypoxia. HL-1 cardiomyocytes were exposed to native LDL [LDL(+)], LDL(-), and LDL(+) enriched in non-esterified fatty acids (NEFA) by phospholipase A2 (PLA2)-mediated lipolysis [PLA2-LDL(+)] or by NEFA loading [NEFA-LDL(+)] under normoxia or hypoxia...
August 2015: International Journal of Biochemistry & Cell Biology
Rebecca E K MacPherson, Sandra J Peters
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...
July 2015: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Lydia-Ann L S Harris, James R Skinner, Trevor M Shew, Terri A Pietka, Nada A Abumrad, Nathan E Wolins
Perilipin 5 (PLIN5) is a lipid droplet protein and is highly expressed in oxidative tissue. Expression of the PLIN5 gene is regulated by peroxisome proliferator-activated receptor-α, fasting, and exercise. However, the effect of increased muscle PLIN5 expression on whole-body energy homeostasis remains unclear. To examine this, we developed a mouse line with skeletal muscle PLIN5 overexpression (MCK-Plin5). We show that MCK-Plin5 mice have increased energy metabolism and accumulate more intramyocellular triacylglycerol but have normal glucose and insulin tolerance...
August 2015: Diabetes
Nils Billecke, Madeleen Bosma, William Rock, Frederik Fleissner, Gerrit Best, Patrick Schrauwen, Sander Kersten, Mischa Bonn, Matthijs K C Hesselink, Sapun H Parekh
Accumulation of fat in muscle tissue as intramyocellular lipids (IMCLs) is closely related to the development of insulin resistance and subsequent type 2 diabetes. Most IMCLs organize into lipid droplets (LDs), the fates of which are regulated by lipid droplet coat proteins. Perilipin 5 (PLIN5) is an LD coating protein, which is strongly linked to lipid storage in muscle tissue. Here we employ a tandem in vitro/ex vivo approach and use chemical imaging by label-free, hyperspectral coherent Raman microscopy to quantify compositional changes in individual LDs upon PLIN5 overexpression...
April 2015: Integrative Biology: Quantitative Biosciences From Nano to Macro
Rachael R Mason, Matthew J Watt
The discovery of perilipin (PLIN) 1 provided a major conceptual shift in the understanding of adipose tissue lipolysis and generated intense interest in lipid droplet biology research. The subsequent discovery of other PLIN proteins revealed unique tissue distribution profiles, subcellular locations, and lipid-binding properties and divergent cellular functions. PLIN5 is highly expressed in oxidative tissues such as skeletal muscle, liver, and heart and is central to lipid homeostasis in these tissues. Studies in cell systems have ascribed several metabolic roles to PLIN5 and demonstrated interactions with other proteins that are requisite for these functions...
March 2015: Trends in Endocrinology and Metabolism: TEM
S V Ramos, P C Turnbull, R E K MacPherson, P J LeBlanc, W E Ward, S J Peters
What is the central question of this study? The aim was to determine whether mitochondrial protein content of perilipin 3 (PLIN3) and perilipin 5 (PLIN5) is increased following endurance training and whether mitochondrial PLIN5 protein is increased to a greater extent in endurance-trained rats when compared with sedentary rats following acute contraction. What is the main finding and its importance? Mitochondrial PLIN3 but not PLIN5 protein was increased in endurance-trained compared with sedentary rats, suggesting a mitochondrial role for PLIN3 due to chronic exercise...
April 1, 2015: Experimental Physiology
Maria Conte, Francesco Vasuri, Enrico Bertaggia, Andrea Armani, Aurelia Santoro, Elena Bellavista, Alessio Degiovanni, Antonia D'Errico-Grigioni, Giovanni Trisolino, Miriam Capri, Martino V Franchi, Marco V Narici, Marco Sandri, Claudio Franceschi, Stefano Salvioli
Sarcopenia, the progressive loss of muscle mass and strength, is a phenomenon characterizing human aging whose etiology is still not clear. While there is increasing evidence for the influence of inter-muscular adipose tissue infiltration in the development of sarcopenia, much less is known about a possible role for intra-muscular triglycerides (IMTG). IMTG accumulate in form of lipid droplets decorated by proteins such as Perilipins (Plins). In skeletal muscle the most abundant are Plin2 and Plin5. In this study we compared the expression of these two Plins in Vastus lateralis muscle samples of subjects of different age, both healthy donors (HD) and patients with limited lower limb mobility (LLMI)...
June 2015: Biogerontology
Rebecca E K MacPherson, Laura M Castelli, Paula M Miotto, Scott Frendo-Cumbo, Amanda Milburn, Brian D Roy, Paul J LeBlanc, Wendy E Ward, Sandra J Peters
A maternal high fat diet (HFD) can have adverse effects on skeletal muscle development. Skeletal muscle PLIN proteins (PLIN2, 3 and 5) are thought to play critical roles in lipid metabolism, however effects of HFD on PLIN and lipases (HSL, ATGL, CGI-58) in mothers as well as their offspring have yet to be investigated. The primary objective of this study was to determine whether maternal HFD would influence skeletal muscle lipase and PLIN protein content in offspring at weaning (19 d) and young adulthood (3 mo)...
February 2015: Lipids
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