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Adipose triglyceride lipase

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https://www.readbyqxmd.com/read/28327588/pharmacological-inhibition-of-adipose-triglyceride-lipase-corrects-high-fat-diet-induced-insulin-resistance-and-hepatosteatosis-in-mice
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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-vldl-tg-fatty-acid-oxidation-during-exercise
#8
Esben Søndergaard, Iben R Andersen, Lars P Sørensen, Lars C Gormsen, Søren Nielsen
INTRODUCTION: 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. Since exercise increase the efficiency of VLDL-TG oxidation, we hypothesized that muscle LPL activity would be a rate-limiting step and predict VLDL-TG FA oxidation during exercise. METHODS: Sixteen healthy, lean subjects (8 men and 8 women) were examined before and during an acute exercise bout (90 min 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
#9
Wen Chen, Youzhao Jiang, Jian Han, Jiongyu Hu, Ting He, Tiantian Yan, Huang Na, 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(PNPLP2), in renal lipid metabolism and kidney disease...
February 14, 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
#10
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
#11
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
https://www.readbyqxmd.com/read/28179319/adipose-triglyceride-lipase-atgl-expression-is-associated-with-adiposity-and-tumor-stromal-proliferation-in-patients-with-pancreatic-ductal-adenocarcinoma
#12
Shane A Grace, Marshall W Meeks, Yongxin Chen, Mona Cornwell, Xianzhong Ding, Ping Hou, Joanne K Rutgers, Susan E Crawford, Jin-Ping Lai
BACKGROUND: Obesity is an established risk factor for the development of pancreatic ductal adenocarcinoma (PDAC). However, the pathophysiology of how increased adiposity increases the risk for PDAC has not been fully elucidated. Adipose triglyceride lipase (ATGL) is a lipase that catabolizes triglyceride hydrolysis and has been implicated in the development of breast cancer. We hypothesized that overweight patients with PDAC would demonstrate higher tumor ATGL expression compared to non-overweight patients with PDAC...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28173868/docosahexaenoic-acid-increases-accumulation-of-adipocyte-triacylglycerol-through-up-regulation-of-lipogenic-gene-expression-in-pigs
#13
Chao-Wei Huang, Yu-Jen Chen, Jui-Ting Yang, Ching-Yi Chen, Kolapo M Ajuwon, Shuen-Ei Chen, Nan-Wei Su, Yu-Shan Chen, Harry J Mersmann, Shih-Torng Ding
BACKGROUND: Changing dietary fatty acid composition in modern diet influences the prevalence of obesity. Increasing evidences suggest favorable effects of n-3 PUFA for protecting against obesity and the metabolic syndrome. However, the regulation of n-3 PUFA in adipose is still unclear. Thus, this study addressed metabolism of different dietary fats in the adipose tissue of porcine model. METHODS: Eight-week-old cross-bred pigs were randomly assigned to three groups and fed a 2% fat diet for 30 days from either soybean oil (SBO), docosahexaenoic acid (DHA) or beef tallow...
February 7, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28159016/%C3%AE-2ap-regulates-vascular-alteration-by-inhibiting-vegf-signaling-in-systemic-sclerosis-the-roles-of-%C3%AE-2ap-in-vascular-dysfunction-in-systemic-sclerosis
#14
Yosuke Kanno, En Shu, Hiroyuki Kanoh, Ayaka Matsuda, Mariko Seishima
BACKGROUND: Systemic sclerosis (SSc) is a connective tissues disease of unknown origin characterized by vascular damage and extensive fibrosis. Recently, we demonstrated that α2-antiplasmin (α2AP) is associated with the development of fibrosis in SSc. We herein investigate the roles of α2AP in vascular dysfunction in SSc. METHODS: Vascular damage in mice was determined by the levels of blood vessels and blood flow. Vascular functions in vascular endothelial cells (ECs) were determined by the levels of tube formation, cell proliferation, and endothelial junction-associated protein (VE-cadherin and PECAM1) production...
February 3, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28146410/almond-skin-polyphenol-extract-inhibits-inflammation-and-promotes-lipolysis-in-differentiated-3t3-l1-adipocytes
#15
Wen-Chung Huang, Chi-Yuan Chen, Shu-Ju Wu
Studies have shown that polyphenols reduce the risk of inflammation-related diseases and upregulates energy expenditure in adipose tissue. Here, we investigated the mechanism of the anti-inflammatory and antiobesity effects of almond skin polyphenol extract (ASP) in differentiated 3T3-L1 adipocytes. The antioxidant effects of ASP were measured based on DPPH radical scavenging activity, Trolox equivalent antioxidant capacity, and total phenolic content. Differentiated 3T3-L1 cells were treated with ASP. Subsequently, lipolysis proteins and transcription factors of adipogenesis were measured...
February 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28112679/mechanism-for-leptin-s-acute-insulin-independent-effect-to-reverse-diabetic-ketoacidosis
#16
Rachel J Perry, Liang Peng, Abudukadier Abulizi, Lynn Kennedy, Gary W Cline, Gerald I Shulman
The mechanism by which leptin reverses diabetic ketoacidosis (DKA) is unknown. We examined the acute insulin-independent effects of leptin replacement therapy in a streptozotocin-induced rat model of DKA. Leptin infusion reduced rates of lipolysis, hepatic glucose production (HGP), and hepatic ketogenesis by 50% within 6 hours and were independent of any changes in plasma glucagon concentrations; these effects were abrogated by coinfusion of corticosterone. Treating leptin- and corticosterone-infused rats with an adipose triglyceride lipase inhibitor blocked corticosterone-induced increases in plasma glucose concentrations and rates of HGP and ketogenesis...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28111231/pigment-epithelium-derived-factor-improves-tnf%C3%AE-induced-hepatic-steatosis-in-grass-carp-ctenopharyngodon-idella
#17
Zhou Yang, Jian Sun, Hong Ji, Xiao-Chen Shi, Yang Li, Zhen-Yu Du, Li-Qiao Chen
Pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNFα), may contribute to hepatic steatosis in the situation of excess lipid accumulation in farmed fish. Pigment epithelium-derived factor (PEDF) is an endogenous anti-inflammatory factor and promotes lipolysis. Accordingly, we isolated PEDF from grass carp and investigated its role in TNFα-induced hepatic steatosis. Sequence analysis showed that PEDF gene, which possesses 8 exons and 7 introns, encodes a protein with 409 amino acids. PEDF was a critical determinant of the transcriptional response to nutrient availability in grass carp...
January 19, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28081221/dietary-lipid-sources-influence-fatty-acid-composition-in-tissue-of-large-yellow-croaker-larmichthys-crocea-by-regulating-triacylglycerol-synthesis-and-catabolism-at-the-transcriptional-level
#18
Hong Qiu, Min Jin, Yi Li, You Lu, Yingmei Hou, Qicun Zhou
An 8-week feeding trial was conducted to evaluate the effects of dietary lipid sources on growth performance, fatty acid composition, rate-limiting enzyme activities and gene expression related to lipid metabolism in large yellow croaker (Larmichthys crocea). Five iso-nitrogenous and iso-lipidic experimental diets were formulated to contain different lipid sources, such as fish oil (FO), soybean oil (SO), linseed oil (LO), rapeseed oil (RO) and peanut oil (PO), respectively. Triplicate groups of 50 fish (initial weight 13...
2017: PloS One
https://www.readbyqxmd.com/read/28058519/stimulation-of-glycerol-kinase-in-grass-carp-preadipocytes-by-epa
#19
Caixia Lei, Jingjing Tian, Hong Ji
This study was conducted to assess the effect of eicosapentaenoic acid (EPA) on grass carp preadipocyte glycerol kinase (GyK) expression, as well as to explore the mechanism. Here, we cloned partial sequence of grass carp GyK gene and analyzed its tissue distribution. The result showed that GyK gene expressed most in the liver, followed by adipose tissue and the kidney. Besides, 400 μM oleic acid (18:1n-9, OA) was used to establish a hypertrophic preadipocyte model. GyK gene expression and enzyme activity were significantly enhanced after model cells were treated with 100 μM eicosapentaenoic acid (20:5n-3, EPA) for 6, 12, and 24 h...
January 5, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/27986537/meaningful-respirometric-measurements-of-ucp1-mediated-thermogenesis
#20
REVIEW
Yongguo Li, Tobias Fromme, Martin Klingenspor
Regarding the enormous interest in brown and brite/beige adipose tissue in the context of metabolic disease, reliable quantification of thermogenesis in these adipocytes is a central issue. This requires an assay specific for uncoupling protein 1 (UCP1) mediated thermogenesis in adherent intact cells. In a recent study we identified a major pitfall associated with established procedures generally applied for this purpose. Meaningful respirometry of UCP1-mediated thermogenesis imperatively requires activation of UCP1 and control over free fatty acid levels...
March 2017: Biochimie
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