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https://www.readbyqxmd.com/read/28811332/de-novo-lipid-synthesis-facilitates-gemcitabine-resistance-through-endoplasmic-reticulum-stress-in-pancreatic-cancer
#1
Saber Tadros, Surendra K Shukla, Ryan J King, Venugopal Gunda, Enza Vernucci, Jaime Abrego, Nina CHaika, Fang Yu, Audrey J Lazenby, Lyudmyla Berim, Jean L Grem, Aaron Sasson, Pankaj K Singh
Pancreatic adenocarcinoma is moderately responsive to gemcitabine-based chemotherapy, the most widely used single agent therapy for pancreatic cancer. While the prognosis in pancreatic cancer remains grim in part due to poor response to therapy, previous attempts at identifying and targeting the resistance mechanisms have not been very successful. By leveraging TCGA dataset, we identified lipid metabolism as the metabolic pathway that most significantly correlated with poor gemcitabine response in pancreatic cancer patients...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28774309/fungal-endophytes-associated-with-viola-odorata-linn-as-bioresource-for-pancreatic-lipase-inhibitors
#2
M Katoch, A Paul, G Singh, S N C Sridhar
BACKGROUND: As per the recent statistical reports of World Health Organisation (WHO), 13% of total global population is obese. Orlistat remains to be the only drug approved for the long term treatment of obesity. Recent findings highlighted severe adverse effects of orlistat that included hepatotoxicity, gall stones, kidney stones and acute pancreatitis. Therefore, search for new drug is required. The investigations based on endophytic natural products would prove pivotal in the global fight against this health issue...
August 3, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28762143/pharmaceutical-interventions-for-diabetes-prevention-in-patients-at-risk
#3
REVIEW
Sudesna Chatterjee, Melanie Davies, Kamlesh Khunti
With the rising incidence and prevalence rates of type 2 diabetes globally, it is imperative that diabetes prevention strategies are implemented to stem the flow of new cases. Successful interventions include both lifestyle modification and pharmaceutical agents, and large, multicentre, randomised, controlled studies in different populations have identified the benefits of both. However, translating positive trial outcomes to the real world is particularly challenging, as lifestyle interventions require regular reinforcement from healthcare professionals to be maintained...
July 31, 2017: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/28724846/metabolic-and-inflammatory-changes-with-orlistat-and-sibutramine-treatment-in-obese-malaysian-subjects
#4
Belqes Abdullah Mohammad Al-Tahami, Ab Aziz Al-Safi Ismail, Zulkefli Sanip, Zurkurnai Yusoff, Tg Muzaffar Tm Shihabudin, Taran Singh Pall Singh, Aida Hanum Ghulam Rasool
INTRODUCTION: Obesity is associated with numerous health problems, particularly metabolic and cardiovascular complications. This study aimed to assess the effects that, nine months of pharmacological intervention with orlistat or sibutramine, on obese Malaysians' body weight and compositions, metabolic profiles and inflammatory marker. METHODS: Seventy-six obese subjects were randomly placed into two groups. The first group received three daily 120 mg dosages of orlistat for nine months (n=39), and the second group received a once daily 10 or 15 mg dosage of sibutramine for nine months (n=37)...
2017: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
https://www.readbyqxmd.com/read/28721138/the-effect-of-orlistat-versus-metformin-on-body-composition-and-insulin-resistance-in-obese-premenopausal-women-3-month-randomized-prospective-open-label-study
#5
Magdalena Kujawska-Łuczak, Katarzyna Musialik, Monika Szulińska, Ewelina Swora-Cwynar, Angelina Kargulewicz, Małgorzata Grzymisławska, Danuta Pupek-Musialik, Paweł Bogdański
INTRODUCTION: Our aim was to evaluate the effects of metformin and orlistat on body composition and glucose-insulin homeostasis in obese premenopausal women. MATERIAL AND METHODS: Seventy-three obese premenopausal Caucasian women aged 32.4 ±8.3 years were treated with either metformin (1000 mg/day; n = 37) or orlistat (360 mg/day; n = 36). Anthropometric parameters were measured using dual-energy X-ray absorptiometry. Glucose tolerance, using the oral glucose tolerance test; insulin resistance, using the homeostasis model assessment (HOMA-IR); and insulin sensitivity, using the Matsuda insulin sensitivity index (ISI Matsuda), were assessed at the commencement of the study and after 3 months...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28708468/a-botanical-composition-from-morus-alba-ilex-paraguariensis-and-rosmarinus-officinalis-for-body-weight-management
#6
Mesfin Yimam, Ping Jiao, Mei Hong, Lidia Brownell, Young-Chul Lee, Hyun-Jin Kim, Jeong-Bum Nam, Mi-Ran Kim, Qi Jia
Obesity is the largest and fastest growing public health catastrophe in the world affecting both adults and children with a prevalence impacting more than one-third of United States (US) adult population. Although the long-term solution lies in lifestyle changes in the form of dieting and exercise, intervention is required for those who are already obese. Unfortunately, treatment options remain quite limited due to associated side effects of conventional therapeutics. As a natural alternative, in this study we describe the beneficial effect of a standardized composition (UP603) comprised of extracts from Morus alba, Ilex paraguariensis, and Rosmarinus officinalis in improving metabolic disorders in high fat diet (HFD) and high fat & high fructose diet (HFFD) induced obese C57BL/6J mice...
July 14, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28705641/design-synthesis-biological-evaluation-and-molecular-modelling-studies-of-novel-diaryl-substituted-pyrazolyl-thiazolidinediones-as-potent-pancreatic-lipase-inhibitors
#7
Sridhar S N C, Deendyal Bhurta, Dharmvir Kantiwal, Ginson George, Vikramdeep Monga, Atish T Paul
A series of novel diaryl substituted pyrazolyl 2,4-thiazolidinediones were synthesized via reaction of appropriate pyrazolecarboxaldehydes with 2,4-thiazolidinedione (TZD) and nitrobenzyl substituted 2,4-thiazolidinedione. The resulting compounds were screened in vitro for pancreatic lipase (PL) inhibitory activity. Two assay protocols were performed viz., methods A and B using p-nitrophenyl butyrate and tributyrin as substrates, respectively. Compound 11e exhibited potent PL inhibitory activity (IC50=4.81µM and Xi50=10...
June 28, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28705172/endocannabinoid-receptor-blockade-reduces-alanine-aminotransferase-in-polycystic-ovary-syndrome-independent-of-weight-loss
#8
Alison J Dawson, Eric S Kilpatrick, Anne-Marie Coady, Abeer M M Elshewehy, Youssra Dakroury, Lina Ahmed, Stephen L Atkin, Thozhukat Sathyapalan
BACKGROUND: Evidence suggests that endocannabinoid system activation through the cannabinoid receptor 1 (CB1) is associated with enhanced liver injury, and CB1 antagonism may be beneficial. The aim of this study was to determine the impact of rimonabant (CB1 antagonist) on alanine aminotransferase (ALT), a hepatocellular injury marker, and a hepatic inflammatory cytokine profile. METHODS: Post hoc review of 2 studies involving 50 obese women with PCOS and well matched for weight, randomised to weight reducing therapy; rimonabant (20 mg od) or orlistat (120 mg tds), or to insulin sensitising therapy metformin, (500 mg tds), or pioglitazone (45 mg od)...
July 14, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/28701318/%C3%A2-liraglutide-for-weight-management
#9
(no author information available yet)
Since 1950, 25 anti-obesity drugs have been withdrawn from use across the world, largely as a result of adverse effects.(1) For several years, orlistat has been the only drug licensed in the UK for weight management.(2) In January 2017, a new presentation of the glucagon-like peptide-1 (GLP-1) analogue liraglutide (▾Saxenda - Novo Nordisk) was launched in the UK as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adults. Here, we review the evidence for its efficacy and safety and consider its place in managing people who are overweight or obese...
July 2017: Drug and Therapeutics Bulletin
https://www.readbyqxmd.com/read/28665967/effects-of-canagliflozin-on-weight-loss-in-high-fat-diet-induced-obese-mice
#10
Wenjun Ji, Mei Zhao, Meng Wang, Wenhui Yan, Yuan Liu, Shuting Ren, Jun Lu, Bing Wang, Lina Chen
Canagliflozin, an inhibitor of sodium glucose co-transporter (SGLT) 2, has been shown to reduce body weight during the treatment of type 2 diabetes mellitus (T2DM). In this study, we sought to determine the role of canagliflozin in body weight loss and liver injury in obesity. C57BL/6J mice were fed a high-fat diet to simulate diet-induced obesity (DIO). Canagliflozin (15 and 60 mg/kg) was administered to DIO mice for 4 weeks. Orlistat (10 mg/kg) was used as a positive control. The body weight, liver weight, liver morphology, total cholesterol (TC) and triglyceride (TG) levels were examined...
2017: PloS One
https://www.readbyqxmd.com/read/28632997/epidemiology-of-obesity-and-pharmacologic-treatment-options
#11
Vignesh Shettar, Sarang Patel, Srividya Kidambi
Prevalence of obesity and its related morbidity have increased to alarming levels in adults and children in the United States and globally. Weight loss results in improvement of much of the obesity-related morbidity. Lifestyle changes such as dietary modifications, increased physical activity, and behavioral therapy form the crux of weight management. However, many individuals need additional assistance (pharmacologic or surgical) to initiate or sustain weight loss. Pharmacologic therapy consists of a number of agents that work by decreasing appetite, gastric emptying, or nutrient absorption or by increasing satiety...
June 1, 2017: Nutrition in Clinical Practice
https://www.readbyqxmd.com/read/28632873/screening-for-obesity-and-intervention-for-weight-management-in-children-and-adolescents-evidence-report-and-systematic-review-for-the-us-preventive-services-task-force
#12
REVIEW
Elizabeth A O'Connor, Corinne V Evans, Brittany U Burda, Emily S Walsh, Michelle Eder, Paula Lozano
Importance: Obesity is common in children and adolescents in the United States, is associated with negative health effects, and increases the likelihood of obesity in adulthood. Objective: To systematically review the benefits and harms of screening and treatment for obesity and overweight in children and adolescents to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, PsycINFO, Cochrane Collaboration Registry of Controlled Trials, and the Education Resources Information Center through January 22, 2016; references of relevant publications; government websites...
June 20, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28624425/antiobesity-antioxidant-and-hepatoprotective-effects-of-diallyl-trisulphide-dats-alone-or-in-combination-with-orlistat-on-hfd-induced-obese-rats
#13
Sivakumar Annamalai, Lavanya Mohanam, Veena Raja, Alwin Dev, Venkataraman Prabhu
The increasing rate of obesity in the past years has become a worldwide concern and it causes many diseases. Even though, Orlistat, a synthetic anti-obesity drug approved by FDA, it causes severe side effects. DATS, a natural product from garlic have gained attention in many biological activities. The aim of the study is to determine the impact of Dially trisulpide (DATS) and its combination with Orlistat therapy on obese animals. 30 male Wistar rats (150-180g) were assigned into 5 groups (n=6). Group 1 rats received normal diet and Group 2 fed with high fat diet (HFD) for 14 weeks...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28615446/lysosome-mediated-degradation-of-a-distinct-pool-of-lipid-droplets-during-hepatic-stellate-cell-activation
#14
Maidina Tuohetahuntila, Martijn R Molenaar, Bart Spee, Jos F Brouwers, Richard Wubbolts, Martin Houweling, Cong Yan, Hong Du, Brian C VanderVen, Arie B Vaandrager, J Bernd Helms
Activation of hepatic stellate cells (HSCs) is a critical step in the development of liver fibrosis. During activation, HSCs lose their lipid droplets (LDs) containing triacylglycerols (TAGs), cholesteryl esters, and retinyl esters (REs). We previously provided evidence for the presence of two distinct LD pools, a preexisting and a dynamic LD pool. Here we investigate the mechanisms of neutral lipid metabolism in the preexisting LD pool. To investigate the involvement of lysosomal degradation of neutral lipids, we studied the effect of lalistat, a specific lysosomal acid lipase (LAL/Lipa) inhibitor on LD degradation in HSCs during activation in vitro The LAL inhibitor increased the levels of TAG, cholesteryl ester, and RE in both rat and mouse HSCs...
July 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28615298/combination-treatment-with-orlistat-containing-nanoparticles-and-taxanes-is-synergistic-and-enhances-microtubule-stability-in-taxane-resistant-prostate-cancer-cells
#15
Joshua J Souchek, Amanda L Davis, Tanner K Hill, Megan B Holmes, Bowen Qi, Pankaj K Singh, Steven J Kridel, Aaron M Mohs
Taxane-based therapy provides a survival benefit in patients with metastatic prostate cancer, yet the median survival is less than 20 months in this setting due in part to taxane-associated resistance. Innovative strategies are required to overcome chemoresistance for improved patient survival. Here, NanoOrl, a new experimental nanoparticle formulation of the FDA-approved drug, orlistat, was investigated for its cytotoxicity in taxane-resistant prostate cancer utilizing two established taxane-resistant (TxR) cell lines...
June 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28588183/orlistat-the-lipase-inhibitor-therapy-in-overweight-and-obese-subfertile-women
#16
D Rahman, S M Shahida, T Hussain, A Begum
This experimental study was carried out to evaluate the efficacy of orlistat (a pancreatic lipase inhibitor) therapy over lifestyle change on weight reduction and ovulation in overweight and obese subfertile women. It was carried out in Department of Gynecology and Obstetrics, Bangabandhu Sheikh Mujib Medical University (BSMMU) Dhaka, Bangladesh from August 2015 to January 2016. Subfertile obese and overweight female patients attending the study centre during study period was considered as study population...
April 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/28559211/effect-of-orlistat-on-plasma-lipids-and-body-weight-a-systematic-review-and-meta-analysis-of-33-randomized-controlled-trials
#17
Amirhossein Sahebkar, Luis E Simental-Mendía, Željko Reiner, Petri T Kovanen, Mario Simental-Mendía, Vanessa Bianconi, Matteo Pirro
Orlistat, an inhibitor of intestinal lipase, promotes body weight reduction. The lipid-lowering efficacy of orlistat is controversial and the effect of orlistat-induced body weight reduction on lipid changes has not been explored in meta-regression analyses. A systematic literature search was conducted to identify randomized controlled trials investigating the efficacy of orlistat on plasma total, low-density lipoprotein and high-density lipoprotein cholesterol, triglycerides and lipoprotein(a) levels. Thirty-three studies were included in the meta-analysis (5522 and 4210 participants in the orlistat therapy and control groups, respectively)...
May 27, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28480405/potential-administration-of-lipoic-acid-and-coenzyme-q-against-adipogensis-target-for-weight-reduction
#18
Maryam A Al-Ghamdi, Hani Choudhry, Huda A Al-Doghather, Etimad H Huwait, Taha A Kumosani, Said S Moselhy
BACKGROUND: Body overweight and obesity were considered as a risk factor for many systemic diseases as diabetic hypertension, cardiovascular diseases, and some cancers. The lipoic acid and Co Q are considered as coenzymes needed for enhancement metabolic rate. The goal of this study is to evaluate the anti-obese effect of lipoic acid alone or combined with Co-Q in rats. MATERIALS AND METHODS: Ninety male albino rats (100-150g) were used in this study, divided into six groups (15 each)...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28462579/pharmacological-management-of-obesity
#19
Amanda Velazquez, Caroline M Apovian
Current management of obesity includes three main arms: behavioral modification, pharmacologic therapy, and bariatric surgery. Decades prior, the only pharmacological agents available to treat obesity were approved only for short-term use (≤ 12 weeks) by the Food and Drug Administration (FDA). However, in the last several years, the FDA has approved several medications for longer term treatment of obesity. This highlights the important progression that we, as a society, better appreciate now the chronicity and complexity of obesity as a disease...
April 28, 2017: Minerva Endocrinologica
https://www.readbyqxmd.com/read/28454342/feasibility-and-antitumor-efficacy-in-vivo-of-simultaneously-targeting-glycolysis-glutaminolysis-and-fatty-acid-synthesis-using-lonidamine-6-diazo-5-oxo-l-norleucine-and-orlistat-in-colon-cancer
#20
Diana Cervantes-Madrid, Guadalupe Dominguez-Gomez, Aurora Gonzalez-Fierro, Enrique Perez-Cardenas, Lucia Taja-Chayeb, Catalina Trejo-Becerril, Alfonso Duenas-Gonzalez
The aim of the present study was to investigate in vivo the feasibility and efficacy of the combination of lonidamine (LND), 6-diazo-5-oxo-L-norleucine (DON) and orlistat to simultaneously target glycolysis, glutaminolysis and de novo synthesis of fatty acids, respectively. The doses of LND and DON used in humans were translated to mouse doses (77.7 mg/kg and 145.5 mg/kg, respectively) and orlistat was used at 240 mg/kg. Three schedules of LND, DON and orlistat at different doses were administered by intraperitoneal injection to BALB/c mice in a 21-day cycle (schedule 1: LND, 0...
March 2017: Oncology Letters
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