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Katie L Whytock, Sam O Shepherd, Anton J M Wagenmakers, Juliette A Strauss
Hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) control skeletal muscle lipolysis. ATGL is present on the surface of lipid droplets (LD) containing intramuscular triglyceride (IMTG) in both the basal state and during exercise. HSL translocates to LD in ex vivo electrically stimulated rat skeletal muscle. Perilipin-2 and perilipin-5 associated lipid droplets (PLIN2+ and PLIN5+ LD) are preferentially depleted during exercise in humans indicating these PLINs may control muscle lipolysis. We aimed to test the hypothesis that in human skeletal muscle in vivo HSL (but not ATGL) is redistributed to PLIN2+ and PLIN5+ LD during moderate-intensity exercise...
March 11, 2018: Journal of Physiology
Oscar Franzén, Raili Ermel, Katyayani Sukhavasi, Rajeev Jain, Anamika Jain, Christer Betsholtz, Chiara Giannarelli, Jason C Kovacic, Arno Ruusalepp, Josefin Skogsberg, Ke Hao, Eric E Schadt, Johan L M Björkegren
RNA editing modifies transcripts and may alter their regulation or function. In humans, the most common modification is adenosine to inosine (A-to-I). We examined the global characteristics of RNA editing in 4,301 human tissue samples. More than 1.6 million A-to-I edits were identified in 62% of all protein-coding transcripts. mRNA recoding was extremely rare; only 11 novel recoding sites were uncovered. Thirty single nucleotide polymorphisms from genome-wide association studies were associated with RNA editing; one that influences type 2 diabetes (rs2028299) was associated with editing in ARPIN ...
2018: PeerJ
Hadjer Namous, Francisco Peñagaricano, Marcello Del Corvo, Emanuele Capra, David L Thomas, Alessandra Stella, John L Williams, Paolo Ajmone Marsan, Hasan Khatib
BACKGROUND: Numerous studies have established a link between maternal diet and the physiological and metabolic phenotypes of their offspring. In previous studies in sheep, we demonstrated that different maternal diets altered the transcriptome of fetal tissues. However, the mechanisms underlying transcriptomic changes are poorly understood. DNA methylation is an epigenetic mark regulating transcription and is largely influenced by dietary components of the one-carbon cycle that generate the methyl group donor, SAM...
February 6, 2018: BMC Genomics
Magdalene K Montgomery, Ruzaidi Mokhtar, Jacqueline Bayliss, Helena C Parkington, Victor M Suturin, Clinton R Bruce, Matthew J Watt
Lipid droplets are critical for the regulation of lipid metabolism, and dysregulated lipid metabolism contributes to the pathogenesis of several diseases including type 2 diabetes. We generated mice with muscle-specific deletion of the lipid droplet-associated protein, perilipin 5 (PLIN5, Plin5MKO ), and investigated PLIN5's role in regulating skeletal muscle lipid metabolism, intracellular signalling and whole-body metabolic homeostasis. High-fat feeding induced changes in muscle lipid metabolism of Plin5MKO mice, which included increased fatty acid oxidation and oxidative stress, but surprisingly, a reduction in inflammation and endoplasmic reticulum (ER) stress...
January 29, 2018: Diabetes
Jianguo Lin, Shizhong Zheng, Alan D Attie, Mark P Keller, David A Bernlohr, William S Blaner, Elizabeth P Newberry, Nicholas O Davidson, Anping Chen
Hepatic stellate cell (HSC) activation occurs along with decreased Perilipin5 (Plin5) and liver fatty acid-binding protein (L-Fabp) expression and coincident lipid droplet (LD) depletion. Conversely, the activated phenotype is reversible in wild type (wt) HSCs upon forced expression of Plin5. Here we asked if L-Fabp expression is required for Plin5-mediated rescue of the quiescent phenotype. Lentiviral Plin5 transduction of passaged L-Fabp-/- HSCs failed to reverse activation markers or to restore lipogenic gene expression and LD formation...
January 9, 2018: Journal of Lipid Research
Peng-Li Zhou, Min Li, Xin-Wei Han, Yong-Hua Bi, Wen-Guang Zhang, Zheng-Yang Wu, Gang Wu
Excessive plasma triglyceride and cholesterol levels promote the progression of several prevalent cardiovascular risk factors, including atherosclerosis, which is a leading death cause. Perilipin 5 (Plin5), an important perilipin protein, is abundant in tissues with very active lipid catabolism, and is involved in the regulation of oxidative stress. Although, in?ammation and oxidative stress play a critical role in atherosclerosis development, the underlying mechanisms are complex and not completely understood...
December 7, 2017: Journal of Cellular Biochemistry
Anne Gemmink, Sabine Daemen, Bram Brouwers, Peter R Huntjens, Gert Schaart, Esther Moonen-Kornips, Johanna Jörgensen, Joris Hoeks, Patrick Schrauwen, Matthijs K C Hesselink
Intramyocellular lipids (IMCL) hamper insulin sensitivity albeit not in endurance-trained athletes (Trained). Compared to type 2 diabetes patients (T2DM), Trained subjects have high levels of Perilipin 5 (PLIN5). Here, we tested if the fraction of PLIN5 coated LDs is a determinant of skeletal muscle insulin sensitivity and contributes to the athlete's paradox. Muscle biopsies were taken from 8 Trained, Lean sedentary, Obese and T2DM subjects. Trained, Obese and T2DM subjects were matched for total IMCL content...
November 7, 2017: Journal of Physiology
M Zappaterra, M Mazzoni, P Zambonelli, R Davoli
The growing request for healthier fatty acid composition of animal products is raising the necessity of a deeper knowledge of the main factors controlling fatty acids storage in muscle and backfat. Perilipin (PLIN) 5, and the whole Perilipin family, seem to play a crucial role in the regulation of lipids deposition as code for proteins coating intracellular lipid droplets surface. Nevertheless, the knowledge of these genes in pig is still incomplete. The present research was aimed at investigating in different pig breeds the PLIN5 gene, analysing its expression level and the associations of the variability in its downstream gene region with pork meat and carcass quality traits...
November 2, 2017: Animal: An International Journal of Animal Bioscience
Xing Gao, Yang Nan, Yuanlin Zhao, Yuan Yuan, Bincheng Ren, Chao Sun, Kaiyu Cao, Ming Yu, Xuyang Feng, Jing Ye
Statins have been proven to be effective in treating non-alcoholic fatty liver disease (NAFLD). Recently, it was reported that statins decreased the hepatic expression of perilipin 5 (Plin5), a lipid droplet (LD)-associated protein, which plays critical roles in regulating lipid accumulation and lipolysis in liver. However, the function and regulation mechanism of Plin5 have not yet been well-established in NAFLD treatment with statins. In this study, we observed that atorvastatin moderately reduced the expression of Plin5 in livers without changing the protein level of Plin5 in the hepatic LD fraction of mice fed with high-fat diet (HFD)...
December 2017: Biochimica et Biophysica Acta
Linda Andersson, Christina Drevinge, Ismena Mardani, Knut T Dalen, Marcus Ståhlman, Martina Klevstig, Annika Lundqvist, Fred Haugen, Martin Adiels, Per Fogelstrand, Jorge Asin-Cayuela, Lillemor Mattsson Hultén, Max Levin, Ewa Ehrenborg, Yun K Lee, Alan R Kimmel, Jan Borén, Malin C Levin
Myocardial triglycerides stored in lipid droplets are important in regulating the intracellular delivery of fatty acids for energy generation in mitochondria, for membrane biosynthesis, and as agonists for intracellular signaling. Previously, we showed that deficiency in the lipid droplet protein perilipin 5 (Plin5) markedly reduces triglyceride storage in cardiomyocytes and increases the flux of fatty acids into phospholipids. Here, we investigated whether Plin5 deficiency in cardiomyocytes alters mitochondrial function...
October 2017: International Journal of Biochemistry & Cell Biology
S O Shepherd, M Cocks, P J Meikle, N A Mellett, A M Ranasinghe, T A Barker, A J M Wagenmakers, C S Shaw
BACKGROUND/OBJECTIVES: In obesity, improved muscle insulin sensitivity following exercise training has been linked to the lowering of diacylglycerol (DAG) and ceramide concentrations. Little is known, however, about how improved insulin action with exercise training in obese individuals relates to lipid droplet (LD) adaptations in skeletal muscle. In this study we investigated the hypothesis that short-term sprint interval training (SIT) and moderate-intensity continuous training (MICT) in obese individuals would increase perilipin (PLIN) expression, increase the proportion of LDs in contact with mitochondria and reduce muscle concentrations of DAGs and ceramides...
December 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
S O Shepherd, J A Strauss, Q Wang, J J Dube, B Goodpaster, D G Mashek, L S Chow
KEY POINTS: The lipid droplet (LD)-associated perilipin (PLIN) proteins promote intramuscular triglyceride (IMTG) storage, although whether the abundance and association of the PLIN proteins with LDs is related to the diverse lipid storage in muscle between trained and sedentary individuals is unknown. We show that lipid infusion augments IMTG content in type I fibres of both trained and sedentary individuals. Most importantly, despite there being no change in PLIN protein content, lipid infusion did increase the number of LDs connected with PLIN proteins in trained individuals only...
August 15, 2017: Journal of Physiology
Tsung-Huang Tsai, Elaine Chen, Lan Li, Pradip Saha, Hsiao-Ju Lee, Li-Shin Huang, Gregory S Shelness, Lawrence Chan, Benny Hung-Junn Chang
Excess triglyceride (TG) accumulation in the liver underlies fatty liver disease, a highly prevalent ailment. TG occurs in the liver sequestered in lipid droplets, the major lipid storage organelle. Lipid droplets are home to the lipid droplet proteins, the most abundant of which are the perilipins (PLINs), encoded by 5 different genes, Plin1 to Plin5. Of the corresponding gene products, PLIN2 is the only constitutive and ubiquitously expressed lipid droplet protein that has been used as a protein marker for lipid droplets...
July 3, 2017: Autophagy
Ali Akoumi, Taha Haffar, Maria Mousterji, Robert Scott Kiss, Nicolas Bousette
We have previously shown that palmitate causes ER stress in primary cardiomyocytes and this was associated with a diffuse lipid staining histology. In contrast, oleate, which was non-toxic, led to the formation of abundant, clearly delineated lipid droplets. The aberrant lipid histology in palmitate treated cells led us to hypothesize that perhaps there was an impairment in lipid droplet formation, which could lead to accumulation of lipids in the ER and consequent ER stress. To test this hypothesis we treated H9C2s (a cardiomyoblast cell line) with either 300µM oleate or palmitate for 8h...
May 15, 2017: Experimental Cell Research
Pengfei Zheng, Zhonglin Xie, Yuan Yuan, Wen Sui, Chao Wang, Xing Gao, Yuanlin Zhao, Feng Zhang, Yu Gu, Peizhen Hu, Jing Ye, Xuyang Feng, Lijun Zhang
Myocardial ischaemia-reperfusion (I/R) injury is a complex pathophysiological process. Current research has suggested that energy metabolism disorders, of which the abnormal consumption of fatty acids is closely related, compose the main pathological basis for myocardial I/R injury. Lipid droplets (LD) are critical regulators of lipid metabolism by LD-associated proteins. Among the lipid droplet proteins, the perilipin family members regulate lipolysis and lipogenesis through different mechanisms. Plin5, an important perilipin protein, promotes LD generation and lowers fatty acid oxidation, thus protecting the myocardium from lipotoxicity...
February 20, 2017: Scientific Reports
Anne Gemmink, Leontine E H Bakker, Bruno Guigas, Esther Kornips, Gert Schaart, A Edo Meinders, Ingrid M Jazet, Matthijs K C Hesselink
A 5-day High-Fat High-Calorie diet (HFHC-diet) reduces insulin-stimulated glucose disposal (Rd) in South Asian, but not Caucasian healthy lean males. We aimed to investigate if differences in myocellular lipid handling are underlying this differential response. A two-step hyperinsulinemic-euglycemic clamp and muscle biopsies were performed in 12 healthy lean Caucasian and South Asian males (BMI < 25 kg/m(2), 19-25 years) before and after a 5-day HFHC-diet (regular diet + 375 mL cream/day; 1275 kcal/day; 94% fat)...
February 14, 2017: Scientific Reports
Camila G Dossi, Cynthia Cadagan, Marcela San Martín, Alejandra Espinosa, Daniel González-Mañán, David Silva, Rodrigo A Mancilla, Gladys S Tapia
Rosa mosqueta (RM) oil is rich in α-linolenic acid (ALA) - a precursor of eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), and it has a high antioxidant activity due to its abundant content of tocopherols. Additionally, it has been observed that RM oil administration prevents hepatic steatosis. Thus, the aim of this study was to demonstrate the antilipogenic mechanism related to RM oil administration in a high-fat diet (HFD) fed mice model by evaluating markers associated with the regulation of lipid droplet metabolism (PLIN2, PLIN5 and PPAR-γ), and proteins associated with lipogenesis (FAS and SREBP-1c)...
February 22, 2017: Food & Function
Claire Laurens, Virginie Bourlier, Aline Mairal, Katie Louche, Pierre-Marie Badin, Etienne Mouisel, Alexandra Montagner, André Marette, Angelo Tremblay, John S Weisnagel, Hervé Guillou, Dominique Langin, Denis R Joanisse, Cedric Moro
Lipid droplets (LD) play a central role in lipid homeostasis by controlling transient fatty acid (FA) storage and release from triacylglycerols stores, while preventing high levels of cellular toxic lipids. This crucial function in oxidative tissues is altered in obesity and type 2 diabetes. Perilipin 5 (PLIN5) is a LD protein whose mechanistic and causal link with lipotoxicity and insulin resistance has raised controversies. We investigated here the physiological role of PLIN5 in skeletal muscle upon various metabolic challenges...
December 6, 2016: Scientific Reports
Aline S M Cesar, Luciana C A Regitano, Mirele D Poleti, Sónia C S Andrade, Polyana C Tizioto, Priscila S N Oliveira, Andrezza M Felício, Michele L do Nascimento, Amália S Chaves, Dante P D Lanna, Rymer R Tullio, Renata T Nassu, James E Koltes, Eric Fritz-Waters, Gerson B Mourão, Adhemar Zerlotini-Neto, James M Reecy, Luiz L Coutinho
BACKGROUND: Lipids are a class of molecules that play an important role in cellular structure and metabolism in all cell types. In the last few decades, it has been reported that long-chain fatty acids (FAs) are involved in several biological functions from transcriptional regulation to physiological processes. Several fatty acids have been both positively and negatively implicated in different biological processes in skeletal muscle and other tissues. To gain insight into biological processes associated with fatty acid content in skeletal muscle, the aim of the present study was to identify differentially expressed genes (DEGs) and functional pathways related to gene expression regulation associated with FA content in cattle...
November 22, 2016: BMC Genomics
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
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