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Elevated lipase

Gabriela Segerer, Daria Engelmann, Alexandra Kaestner, Martin Trötzmüller, Harald Köfeler, Christian Stigloher, Christoph Thiele, Elisabeth Jeanclos, Antje Gohla
Mammalian phosphoglycolate phosphatase (PGP, also known as AUM or glycerol-3-phosphate phosphatase) is a small molecule-directed phosphatase important for metabolite repair and lipid metabolism. Although PGP was first characterized as an enzyme involved in epidermal growth factor (EGF) signaling, PGP protein substrates have remained elusive. Here we show that PGP depletion facilitates fatty acid flux through the intracellular triacylglycerol/fatty acid cycle, and that phosphatidylinositol-4,5-bisphosphate (PIP2), produced in a side branch of this cycle, is critical for the impact of PGP activity on EGF-induced signaling...
March 7, 2018: Biochimica et Biophysica Acta
Cristina Salmerón
White adipose tissue (AT) is the main lipid storage depot in vertebrates. Initially considered to be a simple lipid store, AT has recently been recognized as playing a role as an endocrine organ that is implicated in processes such as energy homeostasis and as a rich source of stem cells. Interest in adipogenesis has increased not only because of the prevalence of obesity, metabolic syndrome and type 2 diabetes in humans, but also in aquaculture because of the excessive fat deposition experienced in some cultured fish species, which may compromise both their welfare and their final product quality...
March 7, 2018: Journal of Experimental Biology
Aafke W F Janssen, Saeed Katiraei, Barbara Bartosinska, Daniel Eberhard, Ko Willems van Dijk, Sander Kersten
AIMS/HYPOTHESIS: Angiopoietin-like 4 (ANGPTL4) is an important regulator of triacylglycerol metabolism, carrying out this role by inhibiting the enzymes lipoprotein lipase and pancreatic lipase. ANGPTL4 is a potential target for ameliorating cardiometabolic diseases. Although ANGPTL4 has been implicated in obesity, the study of the direct role of ANGPTL4 in diet-induced obesity and related metabolic dysfunction is hampered by the massive acute-phase response and development of lethal chylous ascites and peritonitis in Angptl4-/- mice fed a standard high-fat diet...
March 3, 2018: Diabetologia
Laura A McAllister, Christopher R Butler, Scot Mente, Steven V O'Neil, Kari R Fonseca, Justin R Piro, Julie A Cianfrogna, Timothy L Foley, Adam M Gilbert, Anthony R Harris, Christopher J Helal, Douglas S Johnson, Justin I Montgomery, Deane M Nason, Stephen Noell, Jayvardhan Pandit, Bruce N Rogers, Tarek A Samad, Christopher L Shaffer, Rafael Guimaraes da Silva, Daniel P Uccello, Damien Webb, Michael A Brodney
Monoacylglycerol lipase (MAGL) inhibition provides a potential treatment approach to neuroinflammation through modulation of both the endocannabinoid pathway, and arachidonoyl signaling in the central nervous system (CNS). Herein we report the discovery of compound 15 (PF-06795071), a potent and selective covalent MAGL inhibitor, featuring a novel trifluoromethyl glycol leaving group which confers significant physicochemical property improvements as compared with earlier inhibitor series with more lipophilic leaving groups...
March 2, 2018: Journal of Medicinal Chemistry
Mohamed Abu-Farha, Preethi Cherian, Mohamed G Qaddoumi, Irina AlKhairi, Devarajan Sriraman, Muath Alanbaei, Jehad Abubaker
BACKGROUND: Hypertension is a risk factor for both cardiovascular diseases (CVDs) and type 2 diabetes (T2D). Angiopoietin-like proteins (ANGPTLs), mainly ANGPTL3, ANGPTL4 and ANGPTL8, are associated with increased plasma lipid content due to their role in regulating the activity of lipoprotein lipase, a key enzyme in metabolism of the lipoprotein in circulation. Dyslipidaemia is a risk factor for hypertension development; however, the roles of ANGPTL3, ANGPTL4 and ANGPTL8 in subjects with hypertension have not yet been established...
March 1, 2018: Lipids in Health and Disease
Cheng Wang, Shaoqing Chen, Yunxin Wang, Xuerong Liu, Fuqiang Hu, Jihong Sun, Hong Yuan
Insufficient drug release as well as poor drug penetration are major obstacles for effective nanoparticles (NPs)-based cancer therapy. Herein, the high aqueous instability of amorphous calcium carbonate (ACC) is employed to construct doxorubicin (DOX) preloaded and monostearin (MS) coated "Pandora's box" (MS/ACC-DOX) NPs for lipase-triggered water-responsive drug release in lipase-overexpressed tumor tissue to induce a neighboring effect and enhance drug penetration. MS as a solid lipid can prevent potential drug leakage of ACC-DOX NPs during the circulatory process, while it can be readily be disintegrated in lipase-overexpressed SKOV3 cells to expose the ACC-DOX core...
February 27, 2018: Advanced Materials
M M Erdaw, R A Perez-Maldonado, P A Iji
A 3 × 3 + 1 factorial, involving three levels of protease (0, 15,000 or 30,000 PROT/kg) and three levels of phytase (1,000, 2,000 or 3,000 FYT/kg), was used to evaluate the effect of replacing commercial soybean meal (SBM) with raw, full-fat soybean (RFSB) at 75 g/kg of diet for broilers. A control diet was used for comparison. Each treatment was replicated six times, with nine birds per replicate. The concentration of trypsin inhibitors (TIs) in the test diets was approximately 10,193.4 TIU/kg. Regardless of enzyme supplementation, feed intake (FI) and body weight gain (BWG) of birds in the control group were superior to those on the test diets...
February 22, 2018: Journal of Animal Physiology and Animal Nutrition
Minjeong Kim, Jin Myung Park, Sung Joon Lee, Chang Don Kang, MyungHo Kang, Ji Hyun Kim, Seungkoo Lee, Seong Whi Cho
We report a case of acute pancreatitis secondary to pancreatic neuroendocrine tumor. A 46-year old man presented with upper abdominal pain. The serum amylase and lipase were elevated. Abdominal computed tomography (CT) and magnetic resonance cholangiopancreatography revealed a 1.7 cm sized mass at the pancreas body with a dilatation of the upstream pancreatic duct and mild infiltrations of peripancreatic fat. An endoscopic ultrasound-guided fine needle biopsy was performed for the pancreatic mass, but only necrotic tissue was observed on the pathologic examination...
February 25, 2018: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
Tamara Tomin, Katarina Fritz, Juergen Gindlhuber, Linda Waldherr, Bettina Pucher, Gerhard G Thallinger, Daniel K Nomura, Matthias Schittmayer, Ruth Birner-Gruenberger
Adipose triglyceride lipase (ATGL) catalyzes the rate limiting step in triacylglycerol breakdown in adipocytes but is expressed in most tissues. The enzyme was shown to be lost in many human tumors, and its loss may play a role in early stages of cancer development. Here we report that loss of ATGL supports a more aggressive cancer phenotype in a model system where ATGL was deleted in A549 lung cancer cells by CRISPR/Cas9. We observed that loss of ATGL led to triacylglycerol accumulation in lipid droplets, and higher levels of cellular phospholipid and bioactive lipid species (lyso- and ether-phospholipids)...
February 19, 2018: Journal of Proteome Research
Narges Nobakht, Mohammad Ali Faramarzi, Abbas Shafiee, Mehdi Khoobi, Ezzat Rafiee
Iron-carboxylate (MIL-100(Fe)) and HKUST-1 (Cu3 (BTC)2 , BTC = 1,3,5-benzenetricarboxylic acid) as nanoporous metal organic framework supports were compared for immobilization of porcine pancreatic lipase (PPL). These immobilizations improved thermal, pH and operational stability of PPL compared to the soluble enzyme. Stability of MIL-100(Fe) was better than HKUST-1 as support. MIL-100(Fe) encapsulated Keggin phosphotungstic acid H3 PW12 O40 (PW) (PW@MIL-100(Fe)) was synthesized to develop novel enzyme immobilized system and characterized by Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD) and Barrett Joyner Halenda (BJH) analysis...
February 15, 2018: International Journal of Biological Macromolecules
Martine Paquette, Robert A Hegele, Guillaume Paré, Alexis Baass
Familial chylomicronemia syndrome is characterized by severe elevation in serum triglycerides and an increased risk of acute pancreatitis. Although familial chylomicronemia syndrome is mainly caused by mutations in the lipoprotein lipase (LPL) gene, few causal mutations in other genes (ie, APOC2, APOA5, LMF1, and GPIHBP1) have also been reported. In this case report, we present the discovery of a novel mutation in the glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) gene and discuss its pathogenicity through a familial segregation study...
January 31, 2018: Journal of Clinical Lipidology
V E Tóth, Á Fehér, J Németh, I Gyertyán, Z S Zádori, K Gyires
Previous findings showed that inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), degrading enzymes of anandamide (2-AEA) and 2-arachidonoylglycerol (2-AG), reduced the nonsteroidal anti-inflammatory drug-induced gastric lesions. The present study aimed to investigate: i./whether central or peripheral mechanism play a major role in the gastroprotective effect of inhibitors of FAAH, MAGL and AEA uptake, ii./which peripheral mechanism(s) may play a role in mucosal protective effect of FAAH, MAGL and uptake inhibitors...
February 10, 2018: Brain Research Bulletin
Pawel Antoni Kolodziejski, Maciej Sassek, Daniela Chalupka, Natalia Leciejewska, Leszek Nogowski, Pawel Mackowiak, Damian Jozefiak, Katarzyna Stadnicka, Maria Siwek, Marek Bednarczyk, Tomasz Szwaczkowski, Ewa Pruszynska-Oszmalek
Background: In order to discover new strategies to replace antibiotics in the post-antibiotic era in meat-type chicken production, two new synbiotics were tested: (Lactobacillus salivarius IBB3154 plus galactooligosaccharide (Syn1) and Lactobacillus plantarum IBB3036 plus raffinose family oligosaccharides (Syn2). Methods: The synbiotics were administered via syringe, using a special automatic system, into the egg air chamber of Cobb 500 broiler chicks on the 12th day of egg incubation (2 mg of prebiotics + 105 cfu bacteria per egg)...
2018: Journal of Animal Science and Biotechnology
Cheng-Shyuan Rau, Shao-Chun Wu, Peng-Chen Chien, Pao-Jen Kuo, Yi-Chun Chen, Hsiao-Yun Hsieh, Ching-Hua Hsieh, Hang-Tsung Liu
BACKGROUND: In trauma patients, pancreatic injury is rare; however, if undiagnosed, it is associated with high morbidity and mortality rates. Few predictive models are available for the identification of pancreatic injury in trauma patients with elevated serum pancreatic enzymes. In this study, we aimed to construct a model for predicting pancreatic injury using a decision tree (DT) algorithm, along with data obtained from a population-based trauma registry in a Level I trauma center...
February 6, 2018: International Journal of Environmental Research and Public Health
Zul Merali, Christian Cayer, Pamela Kent, Rui Liu, Victor Cal, Cory S Harris, John T Arnason
ETHNOPHARMACOLOGICAL RELEVANCE: The Maya have traditionally used copal, Protium copal, as incense during ceremonies since pre-Columbian times. Anecdotally, copal (when burned as incense), is thought to elicit mentally uplifting and calming effects. The main objective of this study was to determine whether the incense elicits anxiolytic-like behavior in animal models using rats. A second objective was to characterize active constituents and discern potential mechanism(s) of action, specifically the involvement of the GABAergic and endocannabinoid (eCB) systems...
January 29, 2018: Journal of Ethnopharmacology
Bo Zhang, Shu-Liang Li, Hua-Lei Xie, Jia-Wei Fan, Chuan-Wei Gu, Chao Kang, Mu-Jian Teng
The present study investigated the effects of dual specificity phosphatase 1 (DUSP1) gene silencing using lentiviral vector-mediated small interfering (si)RNA on the release of proinflammatory cytokines through the regulation of the mitogen‑activated protein kinase (MAPK) signaling pathway in mice with acute pancreatitis (AP). Two siRNA‑DUSP1 sequences and one scramble siRNA sequence were designed, and the expression of DUSP1 was detected using western blot analysis to screen for the one with a higher interference rate...
January 25, 2018: International Journal of Molecular Medicine
Ruchi Rastogi, Arbind Kumar, Jagdeep Kaur, Varinder Saini, Jasbinder Kaur, Archana Bhatnagar
The genome sequence of Mycobacterium tuberculosis revealed the presence of several hydrolases involved in lipid metabolism including the members of Lip gene family. Rv0646c (LipG) is one of them. It is annotated as putative esterase/lipase because of the presence of consensus sequence 'GXSXG.' The gene was cloned, expressed, and purified in E. coli. It showed 22 U/mg specific activity with pNP-butyrate as a preferred substrate. However, it actively worked on substrates with short chain. The enzyme was optimally active at 50 °C/pH 8...
January 31, 2018: Molecular and Cellular Biochemistry
Thiru Prasanna, Catriona M McNeil, Theresa Nielsen, David Parkin
We report a case of isolated immune-related pancreatic exocrine insufficiency in a patient treated with pembrolizumab for metastatic melanoma. This patient presented with explosive diarrhea and was treated with high dose corticosteroids for possible immune-related colitis. However, biopsies from colon and duodenum did not show any histological evidence of colitis/enteritis. Serum amylase and lipase were not elevated. There was no evidence of pancreatitis or pancreatic metastases on imaging. Significantly lower fecal elastase test on two occasions confirmed the diagnosis of pancreatic exocrine insufficiency...
March 2018: Immunotherapy
Timothy M Reynolds, Clare Mewies, John Hamilton, Anthony S Wierzbicki
AIMS: Lysosomal acid lipase deficiency (LALD) is an autosomal recessive disorder of cholesterol ester storage associated with hepatic disease, cirrhosis and accelerated atherosclerosis. Its prevalence in the general population, patients with dyslipidaemia and raised transaminases is unclear. This study attempted to identify the prevalence of LALD from patients with abnormal results in laboratory databases. METHODS: Electronic laboratory databases were interrogated to identify from clinical biochemistry records patients with a phenotype of low high-density lipoprotein-cholesterol (≤0...
January 22, 2018: Journal of Clinical Pathology
R O Schueler, G White, R L Schueler, J M Steiner, A Wassef
OBJECTIVE: To determine the differences in serum canine pancreatic lipase immunoreactivity between dogs with intervertebral disc herniation and healthy control dogs. MATERIALS AND METHODS: Eighty-four client-owned dogs with intervertebral disc herniation, diagnosed by neurologic examination and imaging, and 18 healthy control dogs. Samples of whole blood were collected within 90 minutes of admission. Serum canine pancreatic lipase immunoreactivity concentrations were measured by a commercial immunoassay and evaluated for association with intervertebral disc herniation, signalment, neurolocalisation and the preadmission administration of glucocorticosteriods or non-steroidal anti-inflammatory drugs...
January 22, 2018: Journal of Small Animal Practice
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