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Adipose triglyceride lipase

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https://www.readbyqxmd.com/read/28433778/novel-lipid-mimetic-prodrugs-delivering-active-compounds-to-adipose-tissue
#1
Andrea Mattarei, Andrea Rossa, Veronica Bombardelli, Michele Azzolini, Martina La Spina, Cristina Paradisi, Mario Zoratti, Lucia Biasutto
Obesity and associated pathologies are a dramatically growing problem. New therapies to prevent and/or cure them are strongly needed. Adipose tissue is a logical target for pharmacological intervention, since it is now recognized to exert an important endocrine function, secreting a variety of adipokines affecting, for example, adiposity and insulin resistance. This proof of principle work focuses on the development of novel lipid-mimetic prodrugs reaching fat deposits by the same lymphatic absorption route followed by dietary triglycerides...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28428482/triglyceride-rich-lipoprotein-lpl-vldl-receptor-and-lp-a-vldl-receptor-pathways-for-macrophage-foam-cell-formation
#2
Sadao Takahashi
Very low-density lipoprotein (VLDL) receptor is a member of the low-density lipoprotein (LDL) receptor family. It binds triglyceride rich lipoprotein (TGRL) but not LDL, because it recognizes apolipoprotein (apo)E only but not apoB. The VLDL receptor functions as a peripheral lipoprotein receptor in concert with lipoprotein lipase (LPL) in heart, muscle, adipose tissue and macrophages. In contrast to the LDL receptor, VLDL receptor binds apo E2/2 VLDL and apoE3/3 VLDL particles, and its expression is not down-regulated by intracellular lipoproteins...
April 19, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28424262/magnesium-reduces-hepatic-lipid-accumulation-in-yellow-catfish-pelteobagrus-fulvidraco-and-modulates-lipogenesis-and-lipolysis-via-ppara-jak-stat-and-ampk-pathways-in-hepatocytes
#3
Chuan-Chuan Wei, Kun Wu, Yan Gao, Li-Han Zhang, Dan-Dan Li, Zhi Luo
Background: Magnesium influences hepatic lipid deposition in vertebrates, but the underlying mechanism is unknown.Objective: We used yellow catfish and their isolated hepatocytes to test the hypothesis that magnesium influences lipid deposition by modulating lipogenesis and lipolysis.Methods: Juvenile yellow catfish (mean ± SEM weight: 3.43 ± 0.02 g, 3 mo old, mixed sex) were fed a 0.14- (low), 0.87- (intermediate) or 2.11- (high) g Mg/kg diet for 56 d. Primary hepatocytes were incubated for 48 h in control or MgSO4-containing medium with or without 2-h pretreatment with an inhibitor (AG490, GW6471, or Compound C)...
April 19, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28404638/kidney-triglyceride-accumulation-in-the-fasted-mouse-is-dependent-upon-serum-free-fatty-acids
#4
Diego Scerbo, Ni-Huiping Son, Alaa Sirwi, Lixia Zeng, Kelli M Sas, Vincenza Cifarelli, Gabriele Schoiswohl, Lesley-Ann Huggins, Namrata Gumaste, Yunying Hu, Subramaniam Pennathur, Nada A Abumrad, Erin E Kershaw, M Mahmood Hussain, Katalin Susztak, Ira J Goldberg
Lipid accumulation is a pathological feature of every type of kidney injury. Despite this striking histological feature, physiological accumulation of lipids in the kidney is poorly understood. We studied whether the accumulation of lipids in the fasted kidney are derived from lipoproteins or non-esterified fatty acids (NEFAs). With overnight fasting, kidneys accumulated triglyceride but had reduced levels of ceramide and glycosphingolipid species. Fasting led to a nearly 5-fold increase in kidney uptake of plasma [14C]oleic acid...
April 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28400046/atgl-gene-deletion-predisposes-to-proximal-tubule-damage-by-impairing-the-fatty-acid-metabolism
#5
Wen Chen, Qiong Zhang, Shiwu Cheng, Jie Huang, Ge Diao, Jian Han
Fibrosis is the final common pathway of chronic kidney disease (CKD). Normal lipid metabolism is integral to renal physiology, and disturbances of renal lipid metabolism are increasingly being linked with CKD, including the fibrosis. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme of lipolysis. In the present study, we used Atgl(-/-) mice to investigate whether ATGL played a role in the regulation of proximal convoluted tubule (PCT) lipid metabolism and renal fibrosis development. ATGL deficiency led to lipid vacuolation of PCT and tubulointerstitial fibrosis, accompanied by massive albuminuria and decreased creatinine clearance rate (Ccr)...
April 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28391974/generation-of-induced-pluripotent-stem-cells-as-disease-modelling-of-nlsdm
#6
D Tavian, S Missaglia, M Castagnetta, D Degiorgio, E M Pennisi, R A Coleman, P Dell'Era, C Mora, C Angelini, D A Coviello
Neutral Lipid Storage Disease with Myopathy (NLSDM) is a rare defect of triacylglycerol metabolism, characterized by the abnormal storage of neutral lipid in organelles known as lipid droplets (LDs). The main clinical features are progressive myopathy and cardiomyopathy. The onset of NLSDM is caused by autosomal recessive mutations in the PNPLA2 gene, which encodes adipose triglyceride lipase (ATGL). Despite its name, this enzyme is present in a wide variety of cell types and catalyzes the first step in triacylglycerol lipolysis and the release of fatty acids...
April 3, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28380348/atgl-promotes-autophagy-lipophagy-via-sirt1-to-control-hepatic-lipid-droplet-catabolism
#7
Aishwarya Sathyanarayan, Mara T Mashek, Douglas G Mashek
Hepatic lipid droplet (LD) catabolism is thought to occur via cytosolic lipases such as adipose triglyceride lipase (ATGL) or through autophagy of LDs, a process known as lipophagy. We tested the potential interplay between these metabolic processes and its effects on hepatic lipid metabolism. We show that hepatic ATGL is both necessary and sufficient to induce both autophagy and lipophagy. Moreover, lipophagy is required for ATGL to promote LD catabolism and the subsequent oxidation of hydrolyzed fatty acids (FAs)...
April 4, 2017: Cell Reports
https://www.readbyqxmd.com/read/28368219/reduced-expression-of-adipose-triglyceride-lipase-decreases-arachidonic-acid-release-and-prostacyclin-secretion-in-human-aortic-endothelial-cells
#8
Monika Riederer, Margarete Lechleitner, Harald Köfeler, Saša Frank
BACKGROUND: Vascular endothelial cells represent an important source of arachidonic acid (AA)-derived mediators involved in the generation of anti- or proatherogenic environments. Evidence emerged (in mast cells), that in addition to phospholipases, neutral lipid hydrolases as adipose triglyceride lipase (ATGL) also participate in this process. OBJECTIVE: To examine the impact of ATGL on AA-release from cellular phospholipids (PL) and on prostacyclin secretion in human aortic endothelial cells (HAEC)...
April 3, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28352352/combination-therapy-with-catechins-and-caffeine-inhibits-fat-accumulation-in-3t3-l1-cells
#9
Xiaojuan Zhu, Licong Yang, Feng Xu, Lezhen Lin, Guodong Zheng
Catechins and caffeine, which are green tea components, have a slimming effect; however, the combinational effect of fat metabolism in 3T3-L1 cells remains unclear. In the present study, 3T3-L1 cells were treated with catechins and caffeine in combination, and it was found that combination therapy with catechins and caffeine markedly reduced intracellular fat accumulation, mRNA expression levels of peroxisome proliferator-activated receptor-γ and CCAAT/enhancer-binding protein α in the early stage of cell differentiation were significantly reduced, and mRNA expression of fatty acid synthetase(FAS) andglycerol-3-phosphate dehydrogenase protein expression levels of FAS were downregulated...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28327588/pharmacological-inhibition-of-adipose-triglyceride-lipase-corrects-high-fat-diet-induced-insulin-resistance-and-hepatosteatosis-in-mice
#10
Martina Schweiger, Matthias Romauch, Renate Schreiber, Gernot F Grabner, Sabrina Hütter, Petra Kotzbeck, Pia Benedikt, Thomas O Eichmann, Sohsuke Yamada, Oskar Knittelfelder, Clemens Diwoky, Carina Doler, Nicole Mayer, Werner De Cecco, Rolf Breinbauer, Robert Zimmermann, Rudolf Zechner
Elevated circulating fatty acids (FAs) contribute to the development of obesity-associated metabolic complications such as insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). Hence, reducing adipose tissue lipolysis to diminish the mobilization of FAs and lower their respective plasma concentrations represents a potential treatment strategy to counteract obesity-associated disorders. Here we show that specific inhibition of adipose triglyceride lipase (Atgl) with the chemical inhibitor, Atglistatin, effectively reduces adipose tissue lipolysis, weight gain, IR and NAFLD in mice fed a high-fat diet...
March 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28258942/late-onset-of-neutral-lipid-storage-disease-due-to-novel-pnpla2-mutations-causing-total-loss-of-lipase-activity-in-a-patient-with-myopathy-and-slight-cardiac-involvement
#11
Sara Missaglia, Lorenzo Maggi, Marina Mora, Sara Gibertini, Flavia Blasevich, Piergiuseppe Agostoni, Laura Moro, Denise Cassandrini, Filippo Maria Santorelli, Simonetta Gerevini, Daniela Tavian
Neutral lipid storage disease with myopathy (NLSDM) presents with skeletal muscle myopathy and severe dilated cardiomyopathy in nearly 40% of cases. NLSDM is caused by mutations in the PNPLA2 gene, which encodes the adipose triglyceride lipase (ATGL). Here we report clinical and genetic findings of a patient carrying two novel PNPLA2 mutations (c.696+4A>G and c.553_565delGTCCCCCTTCTCG). She presented at age 39 with right upper limb abduction weakness slowly progressing over the years with asymmetric involvement of proximal upper and lower limb muscles...
January 17, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28257781/diet-high-in-fructose-promotes-liver-steatosis-and-hepatocyte-apoptosis-in-c57bl-6j-female-mice-role-of-disturbed-lipid-homeostasis-and-increased-oxidative-stress
#12
Youngshim Choi, Mohamed A Abdelmegeed, Byoung-Joon Song
The effects of high (H)-fructose (FR) diet (D) (HFRD) on hepatic lipid homeostasis, oxidative stress, inflammation and hepatocyte apoptosis were investigated in 6-week old female C57BL/6J mice fed a regular chow (ContD) or HFRD (35% fructose-derived calories) for 3 weeks. HFRD-fed mice exhibited increased levels of hepatic steatosis with a significant elevation of serum levels of triglyceride, cholesterol and TNFα compared to ContD-fed mice (P<0.05). HFRD-fed mice exhibited ∼2.7- fold higher levels FAS along with significantly decreased protein levels of adiponection-R2 (∼30%), P-AMPK (∼60%), P-ACC (∼70%) and RXR-α (∼55%), suggesting decreased hepatic fat oxidation compared to controls...
March 1, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28250020/fat-specific-sirt6-ablation-sensitizes-mice-to-high-fat-diet-induced-obesity-and-insulin-resistance-by-inhibiting-lipolysis
#13
Jiangying Kuang, Yuwei Zhang, Qinhui Liu, Jing Shen, Shiyun Pu, Shihai Cheng, Lei Chen, Hong Li, Tong Wu, Rui Li, Yanping Li, Min Zou, Zhiyong Zhang, Wei Jiang, Guoheng Xu, Aijuan Qu, Wen Xie, Jinhan He
Sirt6 is an NAD(+)-dependent deacetylase that is involved in the control of energy metabolism. However, the tissue-specific function of Sirt6 in the adipose tissue remains unknown. Here we showed that fat-specific Sirt6 knockout (FKO) sensitized mice to high-fat diet (HFD)-induced obesity, which was attributed to adipocyte hypertrophy rather than adipocyte hyperplasia. The adipocyte hypertrophy in FKO mice likely resulted from compromised lipolytic activity as an outcome of decreased expression of adipose triglyceride lipase (ATGL), a key lipolytic enzyme...
March 1, 2017: Diabetes
https://www.readbyqxmd.com/read/28239646/mammary-adipocytes-stimulate-breast-cancer-invasion-through-metabolic-remodeling-of-tumor-cells
#14
Yuan Yuan Wang, Camille Attané, Delphine Milhas, Béatrice Dirat, Stéphanie Dauvillier, Adrien Guerard, Julia Gilhodes, Ikrame Lazar, Nathalie Alet, Victor Laurent, Sophie Le Gonidec, Denis Biard, Caroline Hervé, Frédéric Bost, Guo Sheng Ren, Françoise Bono, Ghislaine Escourrou, Marc Prentki, Laurence Nieto, Philippe Valet, Catherine Muller
In breast cancer, a key feature of peritumoral adipocytes is their loss of lipid content observed both in vitro and in human tumors. The free fatty acids (FFAs), released by adipocytes after lipolysis induced by tumor secretions, are transferred and stored in tumor cells as triglycerides in lipid droplets. In tumor cell lines, we demonstrate that FFAs can be released over time from lipid droplets through an adipose triglyceride lipase-dependent (ATGL-dependent) lipolytic pathway. In vivo, ATGL is expressed in human tumors where its expression correlates with tumor aggressiveness and is upregulated by contact with adipocytes...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28211523/pedf-mediates-pathological-neovascularization-by-regulating-macrophage-recruitment-and-polarization-in-the-mouse-model-of-oxygen-induced-retinopathy
#15
Sha Gao, Changwei Li, Yanji Zhu, Yanuo Wang, Ailing Sui, Yisheng Zhong, Bing Xie, Xi Shen
Macrophages have been demonstrated to play a proangiogenic role in retinal pathological vascular growth. Pigment epithelium-derived factor (PEDF) works as a powerful endogenous angiogenesis inhibitor, but its role in macrophage recruitment and polarization is largely unknown. To explore the underlying mechanisms, we first evaluated macrophage polarization in the retinas of the oxygen-induced retinopathy (OIR) mouse model. Compared to that in normal controls, M1- and M2-like macrophages were all abundantly increased in the retinas of OIR mice...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211464/molecular-basis-of-abhd5-lipolysis-activation
#16
Matthew A Sanders, Huamei Zhang, Ljiljana Mladenovic, Yan Yuan Tseng, James G Granneman
Alpha-beta hydrolase domain-containing 5 (ABHD5), the defective gene in human Chanarin-Dorfman syndrome, is a highly conserved regulator of adipose triglyceride lipase (ATGL)-mediated lipolysis that plays important roles in metabolism, tumor progression, viral replication, and skin barrier formation. The structural determinants of ABHD5 lipolysis activation, however, are unknown. We performed comparative evolutionary analysis and structural modeling of ABHD5 and ABHD4, a functionally distinct paralog that diverged from ABHD5 ~500 million years ago, to identify determinants of ABHD5 lipolysis activation...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28207959/lipoprotein-lipase-activity-does-not-predict-very-low-density-lipoprotein-triglyceride-fatty-acid-oxidation-during-exercise
#17
E Søndergaard, I R Andersen, L P Sørensen, L C Gormsen, S Nielsen
Exercise lowers plasma triglyceride levels, but the physiological mechanisms remain not fully elucidated. Lipoprotein lipase (LPL) is a key enzyme in facilitating fatty acid uptake from lipoproteins. As exercise increases the efficiency of very low-density lipoprotein-triglyceride (VLDL-TG) oxidation, we hypothesized that muscle LPL activity would be a rate-limiting step and predict VLDL-TG Fatty acids oxidation during exercise. Sixteen healthy, lean subjects (eight men and eight women) were examined before and during an acute exercise bout (90 minutes at 50% of VO2-max)...
February 16, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28194887/atgl-deficiency-induces-podocyte-apoptosis-and-leads-to-glomerular-filtration-barrier-damage
#18
Wen Chen, Youzhao Jiang, Jian Han, Jiongyu Hu, Ting He, Tiantian Yan, Na Huang, Qiong Zhang, Hao Mei, Yong Liao, Yuesheng Huang, Bing Chen
Abnormal lipid metabolism, renal lipid accumulation and lipotoxicity are associated with the pathological features of glomerulopathy. However, the mechanisms by which lipid accumulation leads to the development or progression of this disease have not been fully elucidated. In this work, we have identified a role for the rate-limiting enzyme in lipolysis, adipose triglyceride lipase (ATGL; also called patatin-like phospholipase domain-containing protein 2), in renal lipid metabolism and kidney disease. ATGL-deficient (Atgl(-/-)) mice displayed albuminuria, accompanied by ectopic deposition of fat in the kidney...
April 2017: FEBS Journal
https://www.readbyqxmd.com/read/28190525/central-action-of-xenin-affects-the-expression-of-lipid-metabolism-related-genes-and-proteins-in-mouse-white-adipose-tissue
#19
Sharma Bhavya, Pei San Lew, Tooru M Mizuno
Xenin is a gastrointestinal hormone that reduces food intake when administered centrally and it has been hypothesized that central action of xenin participates in the regulation of whole-body metabolism. The present study was performed to address this hypothesis by investigating the central effect of xenin on the expression of genes and proteins that are involved in the regulation of lipid metabolism in white adipose tissue (WAT). Male obese ob/ob mice received intracerebroventricular (i.c.v.) injections of xenin (5μg) twice 12h apart...
February 9, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28182091/potential-role-of-angptl4-in-the-cross-talk-between-metabolism-and-cancer-through-ppar-signaling-pathway
#20
REVIEW
Laura La Paglia, Angela Listì, Stefano Caruso, Valeria Amodeo, Francesco Passiglia, Viviana Bazan, Daniele Fanale
The angiopoietin-like 4 (ANGPTL4) protein belongs to a superfamily of secreted proteins structurally related to factors modulating angiogenesis known as angiopoietins. At first, ANGPTL4 has been identified as an adipokine exclusively involved in lipid metabolism, because of its prevalent expression in liver and adipose tissue. This protein regulates lipid metabolism by inhibiting lipoprotein lipase (LPL) activity and stimulating lipolysis of white adipose tissue (WAT), resulting in increased levels of plasma triglycerides (TG) and fatty acids...
2017: PPAR Research
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