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https://www.readbyqxmd.com/read/29449326/fatty-acid-synthase-mediates-egfr-palmitoylation-in-egfr-mutated-non-small-cell-lung-cancer
#1
Azhar Ali, Elena Levantini, Jun Ting Teo, Julian Goggi, John G Clohessy, Chan Shuo Wu, Leilei Chen, Henry Yang, Indira Krishnan, Olivier Kocher, Junyan Zhang, Ross A Soo, Kishore Bhakoo, Tan Min Chin, Daniel G Tenen
Metabolic reprogramming is widely known as a hallmark of cancer cells to allow adaptation of cells to sustain survival signals. In this report, we describe a novel oncogenic signaling pathway exclusively acting in mutated epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) with acquired tyrosine kinase inhibitor (TKI) resistance. Mutated EGFR mediates TKI resistance through regulation of the fatty acid synthase (FASN), which produces 16-C saturated fatty acid palmitate. Our work shows that the persistent signaling by mutated EGFR in TKI-resistant tumor cells relies on EGFR palmitoylation and can be targeted by Orlistat, an FDA-approved anti-obesity drug...
February 15, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29411652/the-safety-of-pharmacologic-treatment-for-pediatric-obesity
#2
Ariana M Chao, Thomas A Wadden, Robert I Berkowitz
Pediatric obesity is a serious public health concern. Five medications have been approved by the Food and Drug Administration (FDA) for chronic weight management in adults with obesity, when used as an adjunct to lifestyle modification. Orlistat is the only FDA-approved medication for pediatric patients aged 12 years and above. Areas covered: This paper summarizes safety and efficacy data from clinical trials of weight loss medications conducted among pediatric samples. Relevant studies were identified through searches in PubMed...
February 7, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29388462/safety-and-tolerability-of-new-generation-anti-obesity-medications-a-narrative-review
#3
Dhiren K Patel, Fatima Cody Stanford
The prevalence of obesity and associated comorbidities is rising. Despite their weight-loss efficacy, new generation anti-obesity medications are only prescribed to a minority of adults with obesity, possibly, which in part may be due to safety concerns. This review presents detailed safety profiles for orlistat, phentermine/topiramate, lorcaserin, naltrexone/bupropion and liraglutide 3.0 mg, and discusses the associated risk-benefit profiles. Two anti-obesity medications presented safety issues that warranted further discussion; phentermine/topiramate (fetal toxicity) and liraglutide 3...
February 8, 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29376439/pharmacotherapy-for-obesity-in-individuals-with-type-2-diabetes
#4
Tariq Chukir, Alpana P Shukla, Katherine H Saunders, Louis J Aronne
Type 2 diabetes (T2DM) is associated with significant morbidity and mortality. Obesity is one of the main risk factors for T2DM and its management requires a multidisciplinary approach, which may include pharmacotherapy. Areas covered: In this paper, data on efficacy, tolerability and safety of FDA-approved pharmacotherapies for obesity (orlistat, phentermine/topiramate extended-release, lorcaserin, bupropion sustained release/naltrexone sustained release and liraglutide) are reviewed, focusing on individuals with type 2 diabetes...
January 29, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29309795/lipase-inhibitor-orlistat-prevents-hepatitis-b-virus-infection-by-targeting-an-early-step-in-the-virus-life-cycle
#5
Knud Esser, Julie Lucifora, Jochen Wettengel, Katrin Singethan, Almut Glinzer, Alma Zernecke, Ulrike Protzer
Hepatitis B Virus (HBV) is a strictly hepatotropic pathogen which is very efficiently targeted to the liver and into its host cell, the hepatocyte. The sodium taurocholate co-transporting polypeptide (NTCP) has been identified as a key virus entry receptor, but the early steps in the virus life cycle are still only barely understood. Here, we investigated the effect of lipase inhibition and lipoprotein uptake on HBV infection using differentiated HepaRG cells and primary human hepatocytes. We found that an excess of triglyceride rich lipoprotein particles in vitro diminished HBV infection and a reduced hepatic virus uptake in vivo if apolipoprotein E is lacking indicating virus transport along with lipoproteins to target hepatocytes...
January 5, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29305933/effects-of-weight-loss-medications-on-cardiometabolic-risk-profiles-a-systematic-review-and-network-meta-analysis
#6
Rohan Khera, Ambarish Pandey, Apoorva K Chandar, Mohammad H Murad, Larry J Prokop, Ian J Neeland, Jarett Berry, Michael Camilleri, Siddharth Singh
BACKGROUND & AIMS: We performed a systematic review and network meta-analysis to evaluate the overall and comparative effects of weight-loss medications, approved by the Food and Drug Administration (FDA) for long-term use, on cardiometabolic risk profiles of obese adults. METHODS: We performed a systematic literature review through February 28, 2017 to identify randomized clinical trials of the effects of FDA-approved weight loss medications (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide), administered to obese adults for 1 year or more, compared with placebo or another active agent...
January 3, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29301630/obesity-pathophysiology-and-management
#7
REVIEW
Kishore M Gadde, Corby K Martin, Hans-Rudolf Berthoud, Steven B Heymsfield
Obesity continues to be among the top health concerns across the globe. Despite our failure to contain the high prevalence of obesity, we now have a better understanding of its pathophysiology, and how excess adiposity leads to type 2 diabetes, hypertension, and cardiovascular disease. Lifestyle modification is recommended as the cornerstone of obesity management, but many patients do not achieve long-lasting benefits due to difficulty with adherence as well as physiological and neurohormonal adaptation of the body in response to weight loss...
January 2, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29275922/effects-of-orlistat-on-blood-pressure-a-systematic-review-and-meta-analysis-of-27-randomized-controlled-clinical-trials
#8
Amirhossein Sahebkar, Luis E Simental-Mendía, Petri T Kovanen, Claudio Pedone, Mario Simental-Mendía, Arrigo F G Cicero
Obesity and high blood pressure (BP) are strongly related and weight loss is mightily associated with a significant BP decrease. The aim of the present meta-analysis was to evaluate and quantify the BP decrease associated with orlistat use in randomized controlled trials. The search included PubMed-Medline, Scopus, Web of Science and Google Scholar databases by up to June 05, 2017, to identify randomized controlled trials investigating the impact of orlistat on blood pressure. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference and 95% confidence interval as summary statistics...
December 14, 2017: Journal of the American Society of Hypertension: JASH
https://www.readbyqxmd.com/read/29243753/extracts-from-the-edible-seaweed-ascophyllum-nodosum-inhibit-lipase-activity-in-vitro-contributions-of-phenolic-and-polysaccharide-components
#9
Ceri Austin, Derek Stewart, J William Allwood, Gordon J McDougall
A polyphenol-rich extract (PRE) from the edible seaweed, Ascophyllum nodosum, inhibited pancreatic lipase activity in an oil-based turbidimetric assay with an IC50 of 200 μg gallic acid equivalents (GAE) perassay) [∼230 μg DW] whereas the known inhibitor, Orlistat, gave an IC50 at 0.4 μg per assay. A phlorotannin-enriched fraction (TRF) purified from the PRE was more potent with an IC50 = 60 μg GAE per assay (∼65 μg DW). When the assay was started by the addition of lipase, both Orlistat and TRF were much less effective which suggests that pre-incubation of enzyme and inhibitor improved inhibition...
December 15, 2017: Food & Function
https://www.readbyqxmd.com/read/29212337/-status-of-pharmacotherapy-in-current-care-of-obese
#10
Petr Sucharda
Weight loss drugs or anti-obesity drugs have a long history but are still far from being successful. Only in two last decades have the drugs been launched, which, when appropriately indicated, may be significantly beneficial to patients in need of weight loss as they are comparably effective to intensive programs to promote changes in eating habits and lifestyles. The combination naltrexone/bupropion is promising for food intake control including the reward mechanism, but the experience with its use has only been short-term...
2017: Casopís Lékar̆ů C̆eských
https://www.readbyqxmd.com/read/29209440/efficacy-of-fenugreek-based-bionanocomposite-on-renal-dysfunction-and-endogenous-intoxication-in-high-calorie-diet-induced-obesity-rat-model-comparative-study
#11
Victoria V Konopelniuk, Ievgenii I Goloborodko, Tetyana V Ishchuk, Tetyana B Synelnyk, Ludmila I Ostapchenko, Mykola Ya Spivak, Rostyslav V Bubnov
Background: Worldwide obesity spread is a global health problem and needs to be further studied. Co-morbidities of obesity include insulin resistance, diabetes mellitus type 2, and dyslipidemia, which are the most frequent contributing factors for metabolic syndrome (MetS), as well as non-alcoholic fatty liver disease and chronic kidney disease. The aim was to study renal function and endogenous intoxication panel on high-calorie diet-induced obesity rat model and perform comparative study of the treatment efficacy of Fenugreek-based bionanocomposite vs antiobesogenic drugs (Orlistat)...
December 2017: EPMA Journal
https://www.readbyqxmd.com/read/29200824/pharmacodynamic-testing-and-new-validated-hplc-method-to-assess-the-interchangeability-between-multi-source-orlistat-capsules
#12
Abdel Naser Zaid, Nihal Zohud, Bushra E'layan, Tasneem Aburadi, Nidal Jaradat, Iyad Ali, Fatima Hussein, Mashhour Ghanem, Aiman Qaddomi, Yara Abu Zaaror
Background: Orlistat is an irreversible inhibitor of the lipase enzyme that prevents trigylcerides from being digested, thereby inhibiting triglyceride hydrolysis and absorption. The resultant reduced calorie uptake enables a positive effect on weight control. Systemic absorption of the drug is, therefore, not necessary for its mode of action. An alternative in vitro study (pharmacodynamic) has been introduced for this drug, as in vivo bioavailability studies are irrelevant with regard to the achievement of the product's intended purposes...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29184702/pharmacological-inhibition-of-diacylglycerol-acyltransferase-1-and-insights-into-postprandial-gut-peptide-secretion
#13
Benjamin S Maciejewski, Tara B Manion, Claire M Steppan
AIM: To examine the role that enzyme Acyl-CoA:diacylglycerol acyltransferase-1 (DGAT1) plays in postprandial gut peptide secretion and signaling. METHODS: The standard experimental paradigm utilized to evaluate the incretin response was a lipid challenge. Following a lipid challenge, plasma was collected via cardiac puncture at each time point from a cohort of 5-8 mice per group from baseline at time zero to 10 h. Incretin hormones [glucagon like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY) and glucose dependent insulinotropic polypeptide (GIP)] were then quantitated...
November 15, 2017: World Journal of Gastrointestinal Pathophysiology
https://www.readbyqxmd.com/read/29172796/effect-of-orlistat-or-metformin-in-overweight-and-obese-polycystic-ovary-syndrome-patients-with-insulin-resistance
#14
Jinghua Song, Xiangyan Ruan, Muqing Gu, Lijuan Wang, Husheng Wang, Alfred Otto Mueck
The aim of this study was to evaluate the effect of orlistat or metformin combined with Diane-35 on anthropometric, hormonal and metabolic parameters in overweight and obese polycystic ovary syndrome (PCOS) patients with insulin resistance (fasting insulin > 10 mIU/L). A total of 240 PCOS women were randomly allocated to orlistat plus Diane-35(OD group), metformin plus Diane-35(MD group), orlistat plus metformin plus Diane-35(OMD group) or Diane-35 (D group). Body weight, BMI, waist and hip circumference, blood pressure, endocrine profile, lipid profile and insulin resistance were assessed at baseline and after 3 months...
November 24, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/29156182/obesity-pharmacotherapy
#15
REVIEW
Katherine H Saunders, Devika Umashanker, Leon I Igel, Rekha B Kumar, Louis J Aronne
Although diet, physical activity, and behavioral modifications are the cornerstones of weight management, weight loss achieved by lifestyle modifications alone is often limited and difficult to maintain. Pharmacotherapy for obesity can be considered if patients have a body mass index (BMI) of 30 kg/m2 or greater or BMI of 27 kg/m2 or greater with weight-related comorbidities. The 6 most commonly used antiobesity medications are phentermine, orlistat, phentermine/topiramate extended release, lorcaserin, naltrexone sustained release (SR)/bupropion SR, and liraglutide 3...
January 2018: Medical Clinics of North America
https://www.readbyqxmd.com/read/29133578/orlistat-induced-oxalate-nephropathy-an-under-recognised-cause-of-chronic-kidney-disease
#16
Laurence Richard Solomon, Andrew Christopher Nixon, Leanne Ogden, Beena Nair
Two patients developed kidney failure due to oxalate deposition in the kidney while taking orlistat. Cessation of orlistat was followed by partial recovery of kidney function. The mechanism by which orlistat causes hyperoxaluria and the management of orlistat-induced oxalate nephropathy is reviewed. We suggest that all patients taking orlistat are at risk of this condition, which may develop insidiously and is easily overlooked. Monitoring of kidney function of patients taking orlistat is warranted.
November 12, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29084164/new-biflavonoids-with-%C3%AE-glucosidase-and-pancreatic-lipase-inhibitory-activities-from-boesenbergia-rotunda
#17
Nutputsorn Chatsumpun, Boonchoo Sritularak, Kittisak Likhitwitayawuid
Roots of Boesenbergia rotunda (L.) Mansf. are prominent ingredients in the cuisine of several Asian countries, including Thailand, Malaysia, Indonesia, India, and China. An extract prepared from the roots of this plant showed strong inhibitory activity against enzymes α-glucosidase and pancreatic lipase and was subjected to chromatographic separation to identify the active components. Three new biflavonoids of the flavanone-chalcone type (9, 12, and 13) were isolated, along with 12 known compounds. Among the 15 isolates, the three new compounds showed stronger inhibitory activity against α-glucosidase than the drug acarbose but displayed lower pancreatic lipase inhibitory effect than the drug orlistat...
October 30, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29078893/autodigestion-by-migrated-trypsin-is-a-major-factor-in-small-intestinal-ischemia-reperfusion-injury
#18
Rabea Verhaegh, Frank Petrat, Lisa Brencher, Michael Kirsch, Herbert de Groot
BACKGROUND: The pathophysiological role of pancreatic digestive hydrolases in intestinal ischemia-reperfusion (I/R) injury is still not clear. Here, we studied whether ischemia-induced injury to the small intestine can be explained by the autodigestion hypothesis. MATERIALS AND METHODS: Mesenteric I/R was induced in rats by superior mesenteric artery occlusion (90 min) and reopening (120 min). Thirty minutes before superior mesenteric artery occlusion, aprotinin (14...
November 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/29061815/orlistat-reduces-proliferation-and-enhances-apoptosis-in-human-pancreatic-cancer-cells-panc-1
#19
Ewa Sokolowska, Malgorzata Presler, Elzbieta Goyke, Ryszard Milczarek, Julian Swierczynski, Tomasz Sledzinski
BACKGROUND/AIM: Pancreatic cancer is a disease with very poor prognosis, and none of currently available pharmacotherapies have proven to be efficient in this indication. The aim of this study was to analyze the expression of fatty acid synthase (FASN) gene as a potential therapeutic target in proliferating human pancreatic cancer cells (PANC-1), and verify if orlistat, originally developed as an anti-obesity drug, inhibits PANC-1 proliferation. MATERIALS AND METHODS: The effects of orlistat on gene expression, lipogenesis, proliferation and apoptosis was studied in PANC-1 cell culture...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29044720/observational-comparative-effectiveness-of-pharmaceutical-treatments-for-obesity-within-the-veterans-health-administration
#20
Ted R Grabarczyk
STUDY OBJECTIVE: To compare the effectiveness of weight-management medications used to assist with weight loss in real-world clinical practice in the Veterans Health Administration (VHA). DESIGN: Retrospective, multicenter, observational cohort study. DATA SOURCE: National VA Corporate Data Warehouse. PATIENTS: A total of 66,035 VA patients aged 18 years or older with a body mass index of 25 kg/m2 or greater who had an initial fill for a study medication (orlistat [6153 patients], phentermine [304 patients], lorcaserin [298 patients], or phentermine-topiramate extended release [233 patients]) or participation in the VA's MOVE! weight-management program with at least three total visits in a clinic coded as a MOVE clinic in the subsequent 24 weeks (59,047 patients) between January 1, 2012, and July 1, 2016...
January 2018: Pharmacotherapy
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