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Variants of the melanocortin-4 receptor (MC4R) gene are the most common cause of monogenic obesity. In this situation; while obesity cannot be controlled with diet and exercise, it was shown that Glucagon-like-peptide-1 receptor agonists (GLP-1 RA) provide weight loss in short term. In this paper, we present our experience with Liraglutide treatment in an adolescent patient carrying MC4R gene variant. A female patient had admitted first at the age of 12.5 years with a complaint of progressive weight gain. She had a marked excess of appetite since infancy. In the physical examination of the pubertal female patient with a body mass index (BMI) of 36.1kg/m2 (3.48 SDS), there was no pathological finding except diffuse acanthosis nigricans. Laboratory examinations revealed only insulin resistance. Weight loss couldn't be achieved with lifestyle changes, metformin and orlistat treatments In genetic examination, a sporadic heterozygous c.206T>G(p.I69R) variant (reported previously) was found in the MC4R gene. GLP-1 RA Liraglutide treatment was initiated and a loss of 19.2% reduction was achieved in the patient's body weight and BMI at the end of 32 weeks. However, the patient, whose treatment compliance was disrupted due to significant gastrointestinal complaints, returned to her former weight within a few months after treatment was stopped. In our case carrying a pathogenic variant in the MC4R gene, decrease of appetite and weight loss were achieved with Liraglutide treatment, but this situation could not be maintained. In such cases, there is a need for effective and tolerable treatment options.

OBJECTIVES: Bionanocomposites (BNCs) are biopolymers or a natural polymers embedded in a combination of two or more different chemicals using natural carriers or bio. BNCs are widely used in drug formulation and in the development of new drugs for various therapeutic drugs, new dosage forms and in pharmacological medicine. MATERIALS AND METHODS: Useful and improved melting was achieved by converting selected Biopharmaceutics Classification System (BCS) class II drug into BNCs using natural carriers such as the gums of Moringa oleifera Lam. and Aegle marmelos (L.) Correa, respectively. The current work focuses on the enhancement of the novel natural polymers such as M. oleifera and A. marmelos, used to prepare BNC for BCS class II orlistat using a microwave system designed for the distribution method. The natural polymer helps improve the melting of the dispersion when it converts them into BNC. Definitions of orlistat, natural carriers, and prepared BNCs were developed and studied comparatively. The fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) study revealed that there was no communication between drug associations and environmental carriers. RESULTS: Crowd reduction studies were conducted to investigate the material that enhances the melting of BNC compounds dissolving and in vitro disposal of BNCs prepared by DSC, scanning electron microscopy, X-ray diffraction studies, and FTIR. BNCs affect orlistat: M. oleifera (OSMO-BNC- 1: 3), orlistat: A. marmelos (OSAM-BNC- 1: 4) is well developed. CONCLUSION: Ornat BNCs developed with M. oleifera and A. marmelos provide significant improvements in dissolve and highlight their use in reducing fortification. Additionally, land melting limits were applied and determined for the melting of BNCs prepared using the Hansen Solubility parameters in particular, Hoy’s, Fedor and Van Krevelen system and it was found that this report there was a significant increase in the melting of batches prepared for BNCs.

Summary A 37-year-old female of South Asian origin was referred to our diabetes clinic for evaluation of an unusual finding during her retinal screening. Her retinal blood vessels appeared white in contrast to the normal pink-red colour. She had type I hyperlipidaemia, confirmed by genotype, and was recently diagnosed with diabetes, secondary to pancreatic insufficiency, for which she had suboptimal control and multiple hospitalisations with recurrent pancreatitis. On examination, she had multiple naevi on her skin; the rest of the examination was unremarkable. The patient did not report any visual disturbances and had intact visual acuity. Investigations showed raised total cholesterol (12.5 mmol/L) and triglycerides (57.7 mmol/L). Following evaluation, the patient was diagnosed with lipaemia retinalis, secondary to type I hyperlipidaemia. The patient was managed conservatively to reduce the cholesterol and triglyceride burdens. However, therapies with orlistat, statin, fibrates and cholestyramine failed. Only a prudent diet, omega-3 fish oil, medium-chain triglycerides oil and glycaemic control optimised with insulin showed some improvements in her lipid profile. Unfortunately, this led her to becoming fat-soluble vitamin deficient; hence, she was treated with appropriate supplementation. She was also recently started on treatment with volanesorsen. Following this, her lipid parameters improved and lipaemia retinalis resolved. Learning points Lipaemia retinalis is an uncommon incidental finding of type I hyperlipidaemia that may not affect vision. Management of associated dyslipidaemia is challenging with minimal response to conventional treatment. Increased awareness of lipaemia retinalis and specialist management is needed as part of regular patient monitoring and personalised management.

Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 is a virus-induced inflammatory disease of the airways and lungs that leads to severe multi-organ damage and death. Here we show that cellular lipid synthesis is required for SARS-CoV-2 replication and offers an opportunity for pharmacological intervention. Screening a short-hairpin RNA sublibrary that targets metabolic genes, we identified genes that either inhibit or promote SARS-CoV-2 viral infection, including two key candidate genes, ACACA and FASN, which operate in the same lipid synthesis pathway. We further screened and identified several potent inhibitors of fatty acid synthase (encoded by FASN), including the US Food and Drug Administration-approved anti-obesity drug orlistat, and found that it inhibits in vitro replication of SARS-CoV-2 variants, including more contagious new variants, such as Delta. In a mouse model of SARS-CoV-2 infection (K18-hACE2 transgenic mice), injections of orlistat resulted in lower SARS-CoV-2 viral levels in the lung, reduced lung pathology and increased mouse survival. Our findings identify fatty acid synthase inhibitors as drug candidates for the prevention and treatment of COVID-19 by inhibiting SARS-CoV-2 replication. Clinical trials are needed to evaluate the efficacy of repurposing fatty acid synthase inhibitors for severe COVID-19 in humans., Pharmacological inhibitors of fatty acid synthase, including the approved anti-obesity drug orlistat, are shown to inhibit replication of SARS-CoV-2 in vitro and in a mouse model of infection in vivo.

Obesity is a globally common metabolic condition that causes or exacerbates many diseases. High-intensity interval training (HIIT) and orlistat may affect cytokines and adipokines related to obesity. The purpose of this study was to investigate the independent and combined effects of 8 weeks of HIIT and orlistat on body weight, body mass index (BMI), neck circumference, aerobic power, interleukin‑6 (IL-6), tumor necrosis factor α (TNF-α), resistin, and adiponectin in young, obese women. 48 obese individuals were randomly divided into 4 groups: control-placebo (n = 12), HIIT-placebo (n = 12), control-orlistat (n = 12), and HIIT-orlistat (n = 12), and received group-specific interventions. Participant blood samples were taken 48 h before the intervention and 48 h after the last training session. Two-way multivariate analysis of covariance (MANCOVA) was used to investigate the effects of interventions, with significance set at P ≤ 0.05. The results showed that HIIT decreased body weight, BMI, neck circumference, TNF‑α, and resistin concentration, while increasing aerobic power, IL‑6, and adiponectin concentration. Orlistat decreased body weight, BMI, neck circumference, and resistin, and increased plasma IL‑6 levels. In conclusion, although the combined effects of HIIT and orlistat were significant in many factors, no synergistic effect was observed, and there appears to be a limit for changes in each factor that can be reached by either HIIT or medication interventions.

Ожиріння є однією з актуальних медико-соціальних проблем сучасності. Відзначається збільшення поширеності ожиріння серед дітей. Кількість дітей у світі віком до 5 років із надлишковою масою тіла та ожирінням становить 44 мільйони. Ожиріння в дитячому віці є фактором ризику для розвитку тяжкої супутньої патології. Дитяче ожиріння — тяжкий прогностичний фактор ожиріння в дорослих. Реєструється підвищений рівень передчасної смерті в дорослих, які страждали від ожиріння в дитинстві. Заходи профілактики та лікування дитячого ожиріння повинні бути спрямовані на всю родину, а не тільки на хвору дитину. З метою профілактики ожиріння слід обмежувати надлишкове вживання калорій. Для підвищення ефективності профілактики ожиріння в дітей вживання енергії потрібно поєднувати з підвищенням фізичної активності. Основним методом лікування ожиріння в дітей є модифікація способу життя, що включає корекцію харчування, призначення фізичних навантажень та поведінкову терапію. Впровадження шкільних програм, що передбачають збільшення фізичної активності та оптимізацію харчування школярів, підвищує ефективність боротьби з дитячим ожирінням. Фармакотерапія при ожирінні в дітей призначається при неефективності програм з модифікації способу життя. Для медикаментозного лікування ожиріння в дітей застосовується орлістат. Ефективність фармакотерапії підвищується при її поєднанні з комплексними програмами з модифікації способу життя. За кордоном при морбідному ожирінні в підлітків у разі неефективності нехірургічного лікування використовується баріатрична хірургія. У результаті оперативного втручання знижується індекс маси тіла, покращується перебіг супутніх захворювань, підвищується якість життя пацієнтів. Баріатрична хірургія пов’язана з ризиком розвитку побічних ефектів, що потребує проведення безперервного моніторингу ускладнень. Для лікування та профілактики ожиріння в дітей необхідним є мультидисциплінарний підхід із залученням спеціалістів різного профілю.

Tetrahydrolipstatin (THL, 1a) has been shown to inhibit both mammalian and bacterial α/β hydrolases. In the case of bacterial systems, THL is a known inhibitor of several Mycobacterium tuberculosis hydrolases involved in mycomembrane biosynthesis. Herein we report a highly efficient eight-step asymmetric synthesis of THL using a route that allowed modification of the THL α-chain substituent to afford compounds 1a through 1e. The key transformation in the synthesis was use of a (TPP)CrCl/Co(2)(CO)(8) -catalyzed regioselective and stereospecific carbonylation on an advanced epoxide intermediate to yield a trans-β-lactone. These compounds are modest inhibitors of Ag85A and Ag85C, two α/β hydrolases of M. tuberculosis involved in the biosynthesis of the mycomembrane. Among these compounds, 10d showed the highest inhibitory effect on Ag85A (34 ± 22 μM) and Ag85C (66 ± 8 μM) and its X-ray structure was solved in complex with Ag85C to 2.5 Å resolution. In contrast, compound 1e exhibited the best-in-class MICs of 50 μM (25 μg/mL) and 16 μM (8.4 μg/mL) against M. smegmatis and M. tuberculosis H37Ra, respectively, using a microtiter assay plate. Combining 1e with 13 well-established antibiotics synergistically enhanced the potency of few of these antibiotics in M. smegmatis and M. tuberculosis H37Ra. Compound 1e applied at concentrations 4-fold lower than its MIC enhanced the MIC of the synergistic antibiotic by 2 to 256-fold. In addition to observing synergy with first-line drugs, rifamycin and Isoniazid, the MIC of vancomycin against M. tuberculosis H37Ra is 65 μg/mL; however, the MIC was lowered to 0.25 μg/mL in the presence of 2.1 μg/mL 1e demonstrating the potential of targeting mycobacterial hydrolases involved in mycomembrane and peptidoglycan biosynthesis.

Background Lipoprotein Lipase (LPL) deficiency is an inherited disorder in which patients develop hypertriglyceridemia that can lead to recurrent pancreatitis. Mainstay of therapy is medical nutritional therapy. Case Report We present a case of a 35-year-old women with LPL deficiency who suffered recurrent hospitalizations for hypertriglyceridemia induced pancreatitis that was treated effectively with Orlistat. Discussion Other agents that have been studied in LPL deficiency are costly and have limiting side effects. Studies have shown Orlistat to be safe and effective for treatment of LPL deficiency in children. No studies have been performed in adults with LPL deficiency. Conclusion Orlistat may be a potential adjunctive treatment in adult LPL deficiency given its availability and favorable safety profile. Further research regarding Orlistat in the setting of LPL deficiency is needed.

Zhen Qu, Yuning Ren, Hongyu Shen, Huihui Wang, Lijie Shi, Deyong Tong Department of Oncology, 970 Hospital of the PLA Joint Logistic Support Force, Yantai, 264001, People’s Republic of ChinaCorrespondence: Deyong TongDepartment of Oncology, 970 Hospital of the PLA Joint Logistic Support Force, No. 7, Zhichu South Road, Zhifu District, Yantai City, Shandong Province, People’s Republic of ChinaEmail tongdypla@tom.comPurpose: Prostate cancer (PCa) is the second leading cause of cancer-related death among men in developed countries. Cabazitaxel (CBZ) is recommended as one of the most active chemotherapy agents for PCa. This study aimed to develop a hyaluronic acid (HA) decorated, cabazitaxel-prodrug (HA-CBZ) and orlistat (ORL) co-loaded nano-system against the prostate cancer in vitro and in vivo.Methods: Cabazitaxel-prodrug was firstly synthesized by conjugating HA with CBZ through the formation of ester bonds. HA contained ORL and CBZ prodrug co-loaded lipid-polymer hybrid nanoparticles (ORL/HA-CBZ/LPNs) were constructed and characterized in terms of particle size, zeta potential, drug loading capacity and stability. The antitumor efficiency and systemic toxicity of LPNs were evaluated in vitro and in vivo.Results: The resulting ORL/HA-CBZ/LPNs were 150.9 nm in particle size with narrow distribution and high entrapment efficiency. The minimum combination index of 0.57 was found at a drug ratio of 1:2 (ORL:HA-CBZ, w/w) in the drug co-loaded formulations, indicating the strongest synergism effect. ORL/HA-CBZ/LPNs demonstrated an enhanced in vitro and in vivo antitumor effect compared with single drug loaded LPNs and free drug formulations.Conclusion: ORL/HA-CBZ/LPNs showed remarkable synergism cytotoxicity and the best tumor inhibition efficiency in mice with negligible systemic toxicity. ORL/HA-CBZ/LPNs can be highly useful for targeted prostate cancer therapy.Keywords: metastatic castration-recurrent prostate cancer, cabazitaxel, prodrug technology, orlistat, hyaluronic acid

From the whole plant of Dendrobium senile, a new phenanthrene namely 2,5,7-trihydroxy-4-methoxyphenanthrene (1) was isolated, together with seven known compounds including moscatin (2), 2,5-dihydroxy-4,9-dimethoxyphenanthrene (3), moscatilin (4), aloifol I (5), 4,4',8,8'-tetramethoxy[1,1'-biphenanthrene]-2,2',7,7'-tetrol (6), 2,2',7,7'-tetrahydroxy-4,4'-dimethoxy-1,1'-biphenanthrene (7) and bleformin G (8). The structure of the new compound was elucidated by analysis of its spectroscopic data. Moscatin (2) and 2,5-dihydroxy-4,9-dimethoxyphenanthrene (3) showed appreciable pancreatic lipase inhibitory effects when compared with the positive control orlistat.

Background : The role of interleukin-10 (IL-10) in humans is controversial because IL-10 has been proposed to exhibit both pro- and anti-inflammatory effects. We aimed to determine the relationships between the changes in these parameters in obese individuals participating in a weight-reduction program. Methods : We measured cardiometabolic parameters including lipid profile and serum IL-10 concentration before and after completion of a 12-week weight-reduction program in 63 non-diabetic obese subjects with a body mass index ≥27 kg/m2 who had comorbid hypertension or dyslipidemia. All the participants were provided with individual intervention sessions designed to implement lifestyle modifications and administered 120 mg orlistat three times daily for 12 weeks. The relationships between changes in serum IL-10 concentration and changes in cardiometabolic risk factors were analyzed. Results : Changes in serum IL-10 concentration were significantly negatively correlated with changes in total cholesterol (r=-0.377), high-density lipoprotein cholesterol (HDL-C; r=-0.377), and low-density lipoprotein cholesterol (LDL-C; r=-0.278) concentrations. However, there were no correlations between changes in serum IL-10 concentration and changes in other cardiometabolic parameters. Conclusion : Serum IL-10 concentration can increase as serum total cholesterol decreases. Additional studies are needed to explore the mechanisms linking changes in serum IL-10 with serum LDL-C and HDL-C concentrations.

Drug delivery in conventional dosage forms often suffers from the drawbacks of repeated drug administration and large fluctuations in blood drug levels. Controlled drug delivery systems are a convenient way of controlling the dosing frequency responsible for rapid absorption and distribution of drug in conventional dosage forms, and are dependent upon two intrinsic properties of the drug, namely, elimination half-life (t1/2) and therapeutic index (TI). The goal is to give a drug at a sufficient rate, frequency and dose so that the ratio Cmax/Cmin in plasma at steady state is always maintained at effective concentrations during the course of therapy, reducing side effects or improving physicochemical and biopharmaceutical properties. The use of polymers provides the potential to control drug delivery both temporally and spatially. The objective of the present investigation was to develop bilayered tablets of orlistat to achieve controlled release and immediate release. The process is predetermined in such a way to release the drug at an IR and CR by using different polymers. Half life of orlistat is 1-2 hrs, as it has been released immediately. This paper mainly focuses on designing the process to release the drug in a controlled manner by using different polymers like sodium alginate, ethyl cellulose, HPMC.

Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers, including lung cancer; however, targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need. In this study, we tested the anticancer activity of orlistat, an FDA-approved anti-obesity drug, in human and mouse cancer cells in vitro and in vivo, and we found that orlistat, as a single agent, inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro. Mechanistically, we found that orlistat reduced the expression of GPX4, a central ferroptosis regulator, and induced lipid peroxidation. In addition, we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2, a molecule regulating the lipid droplet homeostasis, as a novel target of orlistat. Moreover, in a mouse xenograft model, orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control (P < 0.05). Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.

The present work was designed to evaluate the effectiveness of the orlistat drug on some hormones and biochemical parameters in male rats received a high fat diet (HFD). Twenty-four rats were divided into four groups: 1st group administered normal diet, 2nd group administered HFD, the 3rd group administered HFD plus 9.5 mg/kg b.w./day orlistat, and the 4th group administered HFD diet plus 19 mg/kg b.w./day orlistat. The experimental period was for four weeks. At the end of the experiment, blood samples were obtained for biochemical and hormonal assays. The administration of HFD for four weeks increased significantly the weight gain, serum total cholesterol (TC), triglycerides (TAG), low density lipoprotein (LDL-c), glucose, insulin, triiodothyronine (T3), thyroxine (T4), leptin, with the significant decrease in high density lipoprotein (HDL-c), ghrelin, thyrotropin (TSH) and testosterone hormones in the serum as compared with the control group. The treatment with orlistat neutralized the levels of the measured parameters as compared with HFD fed rats and the results were correlated with the dose of orlistat. In conclusion, an improvement was observed in the biochemical and hormonal results by the treatment with orlistat drug.

Obesity is a condition where there is excessive fat in the body. Weight loss can be accomplished by inhibiting fat absorption through the inhibition of pancreatic lipase activity, a key enzyme in fat metabolism. Natural products from plants contain various phytochemical compounds that can act as pancreatic lipase inhibitors. This research was conducted to determine the lipase inhibitor activity of the methanol extract of Mangifera foetida leaves. Mangifera foetida leaves were extracted and then the total phenolic and flavonoid levels were determined. The extract was tested for its ability to inhibit pancreatic lipase in vitro. The inhibitory activities of the extract and Orlistat were measured using p-nitrophenyl palmitate as a substrate at concentrations of 31.25, 62.5, 125, 250, and 500 µg/mL. The results showed that the extracts of young leaves (YL) and mature leaves (ML) contained phenol and flavonoid compounds. The IC50 values of young leaf extract (YL) and mature leaves (ML) were 45.22 and 35.50 µg/ml, respectively. In conclusion, the Mangifera foetida leaf extract can be promoted as a good source of anti-obesity compounds

One of the important inducers of inflammatory responses and accumulation of fat in hepatocytes is free fatty acids which ultimately lead to the development of non-alcoholic fatty liver disease. Patients with non-alcoholic fatty liver disease have high levels of plasma free fatty acids which are usually associated with type 2 diabetes and components of metabolic syndrome including dyslipidemia. Objective of this research is to investigate the effects of orlistat (a lipase enzyme inhibitor) or telmisartan (an angiotensin receptor blocker) on the serum free fatty acids in non-alcoholic fatty liver disease patients taking into consideration the baseline lipid profile.This open-label clinical trial was carried out in the Department of Pharmacology, College of Medicine at the University of Sulaimani in cooperation with Shar Teaching Hospital in Sulaimani city-Kurdistan Region of Iraq. A total number of 74 non-alcoholic fatty liver disease patients were recruited and grouped randomly into group I (n = 25) treated with orlistat (120 mg/day orally) for 12 weeks, group II (n = 24) treated with telmisartan (20 mg/day orally) for 8 weeks, and group III (n = 25) treated with placebo (carboxy- methyl cellulose) once daily. Fasting serum level of free fatty acid and lipid profile including total cholesterol, triglyceride, high-density lipoprotein, and non-high-density lipoproteins were determined.Orlistat and telmisartan significantly reduced the triglyceride-glucose index and free fatty acid levels (P.001) in patients with non-alcoholic fatty liver diseases.Short-term treatment with orlistat or telmisartan produce effective and significant reductions in FFAs in patients with non-alcoholic fatty liver disease compared to placebo. Orlistat effectively reduces the free fatty acid irrespective of the baseline lipid profile.

Background: Clinically significant weight loss improves glycaemic control and cardiovascular disease risk in patients with type 2 diabetes (T2DM). Aim : To identify and assess the efficacy of medical treatments for weight loss in adults with T2DM. Methods: A systematic review was conducted of peer- reviewed literature between July 2004 and July 2020 via PubMed, Embase, Web of Science, medRxiv and Cochrane Central Register of Controlled Trials. Randomised controlled trials (RCTs) in English investigating medical treatments for weight loss in patients with T2DM were included. RCTs of pharmacotherapy withdrawn from the market were excluded. No minimum length of follow-up time was established. Outcomes of interest were changes from baseline in body weight (%), changes from baseline in HbA 1c (%, mmol/mol) and proportion of patients who achieved ≥5% weight loss. Quality assessment was evaluated using the Jadad score. Results : Fifteen RCTs were included with a total of 4,207 participants with T2DM. Interventions included medications approved for obesity management (orlistat, liraglutide, naltrexone-bupropion and phentermine-topiramate) and other agents investigated for the primary purpose of weight loss (topiramate, metreleptin, dapagliflozin and exenatide) compared with placebo. The duration of the intervention varied from 12 to 56 weeks. Placebo-adjusted body weight loss ranged from 2.2% to 7.3%. Furthermore, 30.5–77.0% of patients achieved ≥5% weight loss. Placebo-adjusted change in glycated haemoglobin was 0.3–1.5% (3.3–16.4 mmol/mol). Conclusion : Current evidence demonstrates that pharmacotherapy for weight loss, except for leptin, is associated with weight loss and glycaemic improvement in patients with T2DM.

Pancreatic lipase is a digestive enzyme involved in the hydrolysis of dietary fats. Orlistat, a potent pancreatic lipase inhibitor, is widely prescribed for long-term obesity treatment. Nevertheless, orlistat is reported for severe adverse effects including hepatotoxicity and pancreatitis. In the present study, a novel series of 11 benzyloxy substituted indole glyoxylamides were designed, synthesized and evaluated for in vitro pancreatic lipase inhibitory activity. Three analogues, 10b, 11b and 11c, exhibited potent activity (IC50 ≤ 2.5 µM), with 11b exhibiting a potent IC50 of 1.68 µM comparable to orlistat (IC50 = 0.99 µM). Further, 11b exhibited reversible competitive inhibition with an inhibitory constant value of 0.98 μM. Molecular docking of these analogues was in agreement with in vitro results, wherein the MolDock scores exhibited significant correlation with their inhibitory activity (Pearson’s r = 0.7122). A 50 ns molecular dynamics simulation of 11b-pancreatic lipase complex confirmed the role of extended alkyl interactions along with π-π stacking and π-cation interactions, in stabilizing the ligand (Maximum RMSD ≈ 3 Å) in the active site. Gastro-intestinal absorption and toxicity prediction of the three potent analogues highlighted the suitability of 11b for in vivo experiments. 11b at a dose of 20 mg/kg exhibited anti-obesity efficacy comparable to orlistat (10 mg/kg), wherein the serum triglycerides were found to be 94.95 and 83.85 mg/dL, respectively. Further, faecal triglyceride quantification indicated 11b to act through pancreatic lipase inhibition similar to orlistat. The present study identified a novel pancreatic lipase inhibitory benzyloxy substituted bis(indolyl) glyoxylamide 11b, with promising anti-obesity activity. Communicated by Ramaswamy H. Sarma

Purpose: To assess the anti-obesity effect of liquid chromatography mass spectrometry (LCMS) profiled ethylacetate fraction (EF) of Anthocleista vogelii Planch on pancreatic lipase activity in vitro, and on obesity-related hormones in high-fat diet (HFD)-induced obese rats. Methods: Chromatographic analysis of EF to identify bioactive compounds was performed using LCMS electrospray ionization mass spectrometry (ESI-MS) positive mode. Thirty Sprague–Dawley rats were divided into 5 groups (n = 6). Group 1 was fed normal pellet diet, while groups 2 - 5 were fed high-fat diet (HFD) for 14 weeks. The rats were treated for 4 weeks from week 10 with 125 mg/kg of EF (group 3), 250 mg/kg of EF (group 4) or 100 mg/kg of orlistat (group 5). Results: Seven alkaloids were identified in EF, namely, 10-hydroxycamtothecin, moschamindole, camptothecin, moschamine, N6-cis-p-coumaroylserotonin, sinomenine and desacetylcolchicine. The EF of A. vogelii exhibited inhibitory activity against pancreatic lipase with half-maximal inhibitory concentration (IC50) of 8.76 ± 0.110 µg/mL. Rats treated with EF (125 and 250 mg/kg) of A. vogelii showed significantly (p < 0.05) decreased feed intake, body weight, leptin and insulin, when compared to HFD controls. Cortisol, serotonin and noradrenaline were significantly (p < 0.05) increased, but changes in thyroid hormones levels in EF-treated rats were not significant (p > 0.05) when compared to HFD controls. Conclusion: The EF of A. vogelii demonstrate anti-obesity activities by inhibiting pancreatic lipase, elevating serotonin and noradrenaline, and increasing leptin sensitivity, leading consequently to decreased body weight of rats. However, the clinical use of EF of A. vogelii as an antiobesity herbal remedy requires further studies on its mechanisms of action.

Objective: High lipophilicity and extensive hepatic metabolism limit oral application of orlistat in obesity treatment. Orlistat-loaded chitosan nanoparticles (CONPs) were optimized by 3-factor 3-level Box–Behnken design (BBD) and surfaced engineered to address limitations. Methods: CONPs were prepared by ionic gelation method. Amounts of chitosan (X1), sodium tripoly phosphate (X2), and orlistat (X3) were selected as independent factors, whereas % entrapment efficiency (Y1) and % drug release (Y2) were employed as responses in BBD. Three-dimensional response surface plots were run to understand the main interaction and quadratic effects of independent variables. Further optimized formulation was surface engineered by Eudragit L-100 (ECONPs) and characterized by FTIR, DSC, XRD, particle size, zeta potential, and SEM. Entrapment efficiency, release kinetics, stability, and in vitro cell line studies were carried out. Results: ECONPs were produced with an average size of 534.6 nm, zeta potential of +5.7 mV, EE of 78.62%, and DR of 80.86%. Eudragit coated CONPs anchored the release of orlistat at pH 6.8 desirable for duodenal targeting. Orlistat was released with low, burst, and sustained release manner over 24 h period followed first-order kinetics with Higuchi model with drug content of 84.87% and 78.44% of release. ECONPs possessed lipase inhibition with IC50 value of 8.0 μg/ml and viability against selected cell lines with CTC50 values (26.32–32.21 μg/ml). Conclusion: BBD was a promising tool in elucidating the insights of formulation variables of CONPs. ECONPs fulfilled the rationale of orlistat release, lipase inhibition, and viability against selected cell lines.

The burden of obesity is increasing all over the world. Except for Orlistat, no effective anti-obesity drug is currently available. Therefore, a search for the new anti-obesity compound is need of time. This study demonstrates macromolecular interaction and inhibitory effect of pentacyclic triterpenoids (PTT) on pancreatic lipase (PL). In the present study PTTs from endophytic Colletotrichum gigasporum were found to show significant inhibitory activity against PL with IC50 of 16.62 ± 1.43 μg/mL. The PTT isolated through bioassay-guided isolation showed a dose-dependent (R2 = 0.915) inhibition against porcine PL and the results were comparable with the standard (Orlistat). Based on inhibition kinetic data, the gradual increase in Km (app) with increasing PTT concentration indicated that the mode of interaction of PTT with PL was a competitive type, and it directly competed with the substrate (pNPB) for the active site of PL. In vivo studies in Wistar rats at the oral dose (100 mg/kg body weight) of PTT significantly decreased (p

Background: Obesity is a major problem in Saudi Arabia. Pharmaceutical solutions were sought for treatment. Chemical formula might lead to major health side effects. Meanwhile, the use of herbal formula is alleged to be safe. Green tea and apple vinegar are some of these products. Objective: The study aimed to measure the effect of green tea and apple vinegar on obesity and liver status compared to medical drugs. Materials and methods: Thirty-six adult male albino rats were divided into normal control, and other five groups fed on high caloric and hyperlipidemic diets. They were control positive and the rest 4 groups were treated with different formula (green tea, apple cider vinegar, orlistat and chitocal). Results: All treated groups showed significant decrease in body weight when compared to control positive. Rats administered with orlistat and chitocal showed the highest significant decrease in body weight gain (BWG) when compared to control positive. Moreover, all tested groups enhanced liver functions especially chitocal and apple cider vinegar groups which showed the highest effect in ALT. Orlistat and green tea groups came in second level. Conclusion: Although, no poor effect of chemical drugs found, natural products can provide the positive effect with no risk. Apple cider vinegar was the best natural weight control formula.

Yu-Jin Kwon,1– 3 Hyangkyu Lee,4 Chung Mo Nam,5 Hyuk-Jae Chang,6 Young-Ran Yoon,7 Hye Sun Lee,8 Ji-Won Lee1 1Department of Family Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea; 2Department of Medicine, Graduate School of Yonsei University College of Medicine, Seoul, Republic of Korea; 3Department of Family Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea; 4 Yonsei University College of Nursing, Mo-Im Kim Nursing Research Institute, Seoul, Republic of Korea; 5Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 6Department of Internal Medicine, Division of Cardiology, Severance Cardiovascular Hosp, Yonsei University College of Medicine, Seoul, Republic of Korea; 7Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 8Biostatistics Collaboration Unit, Department of Research Affairs, Yonsei University College of Medicine, Seoul, Republic of KoreaCorrespondence: Ji-Won LeeDepartment of Family Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, 211 Eonju‐ro, Gangnam‐gu, 06273, Seoul, 135-720, Republic of KoreaTel +82 2 2019 3480Fax +82 3462 8209Email indi5645@yuhs.acBackground: In clinical practice, concomitant treatment of orlistat with phentermine is commonly used off-label. However, clinical trials have not been performed to evaluate whether their combination improves metabolic parameters and cardiovascular risk factors other than weight loss. Therefore, we aimed to compare the efficacy of concomitant administration of orlistat and phentermine versus phentermine alone on the endothelial cell function in overweight and obese adults with back pain.Methods: We conducted a 12-week, double-blinded, placebo-controlled clinical trial involving 114 patients with a body mass index of ≥ 30 (obese) or ≥ 27 (overweight) with weight-related comorbidities. We randomly assigned patients in a 1:1 ratio to receive orlistat (120mg) three times daily and phentermine (37.5mg) once daily, or a placebo three times daily and phentermine (37.5mg) once daily. Primary endpoint was changes in endothelium-dependent vasodilatation measured using ultrasound assessment of flow-mediated dilatation (FMD). Differences within groups after intervention were compared using the paired t-test or Wilcoxon signed-rank test. Differences in changes between the groups were calculated using an analysis of covariance after adjusting for each baseline value.Results: Mean weight loss during the 12-week study period was 6.1kg in the orlistat/phentermine group and in the placebo/phentermine group. Adjusted mean changes in total and non-high-density lipoprotein cholesterol were significantly greater in the orlistat/phentermine group than in the placebo/phentermine group. Adjusted mean changes in endothelium-dependent FMD were significantly greater in the orlistat/phentermine group than in the placebo/phentermine group (4.97± 0.98% vs 2.05± 0.99%, respectively; p=0.038). Changes in endothelium-independent nitroglycerin-mediated dilatation were not significantly different between the groups.Conclusion: Orlistat/phentermine significantly improved the vascular endothelial cell function compared with phentermine alone. Orlistat might have beneficial effects on the decrease of the risk of cardiovascular disease, especially in overweight and obese patients with comorbidities.Trial Registration: ClinicalTrails.gov number, NCT03675191.Keywords: obesity, orlistat, phentermine, endothelial cell function

Objectives Pre-pregnancy obesity is a serious epidemics concern that negatively affects the neurodevelopmental of the offspring. Elateriospermum tapos (E. tapos) commonly used to enhance weight loss in obesity treatment. This study was aimed to investigate the influence of E. tapos supplement in obese maternal prior pregnancy on the offspring’s bodyweight, lipid metabolism and memory function. Methods Thirty female Sprague Dawley rats were used. Six rats were assigned to the normal diet group (DND). The remaining rats were fed with a high-fat and cafeteria diet (HFCD) to generate obesity for 5 weeks. Obese rats were further divided into four groups: Negative Control (DNC; HFCD), Positive Control (DPC; Orlistat 200 mg/kg), treatment 1 (DTX1; E. tapos seed 200 mg/kg) and treatment 2 (DTX2, E. tapos shell 200 mg/kg) were given daily, for 6 weeks prior to mating. At weaning, offspring of both genders were designated into six groups according to their dam’s group (n=6/group). All groups were fed with a cafeteria diet except for the control group. Memory tasks for object and place recognition were conducted on offspring at eighth weeks of age. The offspring were cull at the 12th week of age for their blood sample. Results Both offspring genders from DTX2 significantly reduce bodyweight, calorie intake and triglyceride level. In memory tasks, offspring from DTX2 showed a significant increase in exploration rate in place test as compared to offspring from the DNC group. Conclusions This study highlights E. tapos shell as an anti-obesity agent and protecting memory deficit in obese dam’s offspring.

The present study investigates the anti-obesity activity of Luffa cylindrica in progesterone induced obesity model. Swiss albino mice were grouped into 7 (n = 6). Obesity was induced by administration of progesterone (10 mg/kg s.c.) for 28 days. Normal group received ad libitum and water. Disease control, positive control and treatment groups received progesterone (10 mg/kg s.c.). Further positive control group received Orlistat (10 mg/kg p.o). Treatment groups received hydro-alcoholic and fractionation extract of Luffa cylindrica at doses 400, 200, 100 mg/kg b.w. Food and water intake were recorded daily, Body weight, BMI and blood glucose were checked weekly. On completion of the study, animals were sacrificed and blood serum being utilized to accesses in vitro to estimate the various biochemical parameters. Serotonin levels and antioxidant biomarkers were also estimated. Histopathology of liver and adipose tissue was studied. After the 28 days of treatment with plant extract and fraction, it was observed to improve the progestrogen-induced obesity by improving BMI, body weight, brain serotionin, locomotor activity, blood glucose level, anti-oxidant biomarkers, and lipid profile. After assimilating the In vivo and in vitro studies Luffa cylindrical extract highlighted the antilipidemic, anti-hyperglycaemic, antioxidant potential in hormone-induced obesity.

Background and Objective: Orlistat drug is one of the most criticalanti-obesity drugs that widely used around the world. The aim of this study was evaluation the effect of orlistat on the expression of OCT4, Nanog, SOX2, and KLF4 genes in the colorectal cancer SW40 cell line. Materials and Methods: SW40 cell line was cultured in DMEM medium contained orlistat for 24h, and cell viability was assessed by MTT assay. The fold changes of expression of OCT4, NANOG, KLF4, and SOX2 at mRNA level against β-actin were determined by real-timePCR. Two-sample t-test and one-way ANOVA were used to compare the mean of expression of different genes in different groups and different concentrations; a significant level of 0.05 was considered in all tests. Results: Our results showed a significant difference in cell viability, when different doses of Orlistat were used for 24 hour. concentrations of 25 and 100 μM reduce significantly the expression of OCT4 (p

OBJECTIVE The aim: To study morphometric and electron microscopic changes in the parenchyma of rat lymph nodes under the action of sodium glutamate and its correction by orlistat. PATIENTS AND METHODS Materials and methods: The article presents and analyzes the data of an experimental study conducted on 66 white male rats and females of reproductive age. Experimental animals are divided into 4 groups. RESULTS Results: After six weeks of exposure to monosodium glutamate, there was a significant decrease in the relative area of the cortical substance in the lymph nodes of white male and female rats by 11.95% and 9.31% and, respectively, an increase in the relative area of the medullary substance by 18.76% and 14.7% in compared with an intact group of animals. After six weeks of sodium glutamate and the next six weeks of the standard diet of vivarium and orlistat, the relative area of the cortical substance in the lymph node parenchyma was 2.55% and 0.38% more than the parameters of the intact group of animals, respectively. Accordingly, the relative area of the medullary substance decreased and was 4.01% and 0.59% less compared to the intact group of animals. CONCLUSION Conclusions: Electron microscopic examination showed that monosodium glutamate causes changes in the parenchyma of the lymph nodes as in a high-calorie diet. The introduction of orlistat (xenical) leads to a partial restoration of the structural organization, and hence the function of this organ.

Background: Increased lipase activity can increase the amount of monoglycerides and fatty acids absorbed by the body, this is what affects obesity. If pancreatic lipase activity is inhibited, the production of fatty acids will decrease, consequently the level of fat in the blood will also decrease. Objective: To study anti obesity potential of a single herb or a mixture of green tea and other herbs (Syzygium polyanthum. Lv, Artocarpus communis.Lv, Cinnamomum verum..Lv, Manilkara zapota.Lv, Tectona grandis.Lv) by the in vitro inhibition assay of the lipase enzyme activity Method : A single (8 herbs) or a mixture of three herbs powder (12 formulas) was put into a tea bag with a total weight of 1.5 g to be brewed in 100 mL bottled mineral water at 70⁰-90⁰C for 10 minutes. In vitro lipase enzyme inhibition assay were conducted to measure the ability of these samples as lipase inhibitor. Orlistat used as positive lipase inhibitor. Results : There wa s a difference results of lipase inhibition activity between the sample of a single and a mixture of herbs. I nterestingly, the results shows that formula 3 (mixture of green tea, Manilkara zapota and cinnamon) . has 53.942 % inhibition , formula 9 ( a mixture of green tea, Syzygium polyanthum and cinnamon) has 67.322 % inhibition and formula 12 ( a mixture of green tea, Tectona grandis and cinnamon) has 56.612 % inhibition which close to lipase inhibitory activity by standard Orlistat. Conclusion: The mixture of green tea and two other herbs has a lipase inhibitory activity similar to Orlistat , when compared to the single herb. The highest lipase inhibitory activity is found in formula 9 .

Obesity is among the leading causes of morbidity and mortality worldwide and its prevalence continues to increase globally. Because obesity is a chronic, complex, and heterogeneous disease influenced by genetic, developmental, biological, and environmental factors, it is necessary to approach obesity with an integrated and comprehensive treatment strategy. As it is difficult to achieve and sustain successful long-term weight loss in most patients with obesity through lifestyle modifications (e.g., diet, exercise, and behavioral therapy), pharmacological approaches to the treatment of obesity should be considered as an adjunct therapy. Currently, four drugs (orlistat, naltrexone extended-release [ER]/bupropion ER, phentermine/topiramate controlled-release, and liraglutide) can be used long-term (>12 weeks) to promote weight loss by suppressing appetite or decreasing fat absorption. Pharmacotherapy for obesity should be conducted according to a proper assessment of the clinical evidence and customized to individual patients considering the characteristics of each drug and comorbidities associated with obesity. In this review, we discuss the mechanisms of action, efficacy, and safety of these available long-term anti-obesity drugs and introduce other potential agents under investigation. Furthermore, we discuss the need for research on personalized obesity medicine.

The present study investigated the synergistic potential of methanol extract/fractions of Camellia sinensis (L.) Kuntze (CSM) leaves and orlistat on inhibition of Pancreatic Lipase (PL). Since PL is responsible for 50–70% of dietary fats digestion, its inhibition is considered as a promising target for the management of obesity. A synergy guided fractionation strategy has been incorporated with the help of combination index (CI) and isobologram methods. CSM exhibited a potential synergistic activity in combination with orlistat (CI value: 0.66). Amongst the subfractions of CSM, polyphenol-rich fraction exhibited a greater synergistic potential (CI-0.35) than remaining fractions. HPLC analysis identified epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) as major phytochemicals in polyphenol-rich fraction and the most active subfractions (F6 and F7). Two drug and three-drug combinations of these phytochemicals were investigated by partnering with orlistat. The three-drug combination (orlistat-EGCG-ECG) exhibited a greater synergistic potential (CI value-0.17) than the two-drug combinations of EGCG-orlistat and ECG-orlistat (CI values of 0.40 & 0.71, respectively). The resultant orlistat-EGCG-ECG combination resulted in a 12.11-fold dose reduction index for orlistat. Thus, synergistic drug combinations of polyphenol-rich fraction along with orlistat offers the prospect to enhance the orlistat anti-obesity efficacy in a decreased dose level, that will help to reduce its associated toxicities while maintaining its efficacy.

Background and aim Chrysin is a flavonoid found in plant extracts from Passiflora species, honey and propolis. It has demonstrated anti-adipogenic activity in vitro but there are no studies substantiating the anti-obesity activity of chrysin in vivo. Experimental procedure The pancreatic lipase (PL) inhibitory potential of chrysin was determined by preliminary in silico screening and further confirmed by in vitro PL inhibitory assay and oral fat tolerance test (OFTT). The effect of chrysin on acute feed intake and sucrose preference test was determined in normal rats. Obesity was induced by feeding of high fructose diet (HFD) to the rats. The rats were divided into six groups: normal control, HFD control, orlistat and three doses of chrysin (25, 50 and 100 mg/kg body weight). Body weight, body mass index (BMI), abdominal circumference/thoracic circumference (AC/TC) ratio, calorie intake, adiposity index, fecal cholesterol, locomotor activity and histopathology of the adipose tissue of the rats were evaluated. Results Chrysin showed good affinity to PL with competitive type of inhibition. It significantly reduced serum triglycerides in OFTT. Chrysin also significantly reduced acute feed intake and sucrose preference in rats. Chrysin significantly decreased the body weight, BMI, AC/TC ratio, adiposity index, calorie intake while it significantly increased the fecal cholesterol and locomotor activity of the rats. Chrysin was found to reduce the size of the adipocytes when compared to the HFD control group. Conclusion Thus, chrysin exerted anti-obesity effect by inhibiting PL, reducing sucrose preference, reducing calorie intake and increasing the locomotor activity of rats., Graphical abstract Image 1021, Highlights • Chrysin was found to be competitive inhibitor of pancreatic lipase. • Chrysin reduced the body weight of rats. • Chrysin reduced calorie intake of rats. • Chrysin increased the locomotor activity of obese rats. • Chrysin reduced the hypertrophy of adipocytes.

Obesity is an increase in body weight that exceeds normal and the risk of serious illness. Bambu Tali leaves ( Gigantochloa apus (Schult.) Kurz) contain flavonoids, tannins, and saponins, which can inhibit the absorption of fatty acids in the digestive tract and excrete them through feces to lose weight. This study examines the tea activity of the Bambu Tali leaves in inhibiting weight gain, total cholesterol, and triglyceride levels of obese Wistar rats fed with a high-fat diet (HFD). A total of 30 Wistar rats were divided into 6 groups: normal control (standard feed), negative control (HFD), positive control (HFD + Orlistat), and 3 groups of tea doses of Bambu Tali leaves (HFD + 360, HFD + 720, HFD + 1440 mg/kg BW). HFD was given together with the Bambu Tali leaf tea for 35 days. On the 36th day, the blood sample was taken to measure cholesterol and triglyceride levels. The weighing was conducted weekly. The results showed that giving HFDincreased body weight significantly, total cholesterol, and triglyceride levels (p

Effective treatments for pediatric obesity are limited. Glucagon-like peptide-1 receptor (GLP-1R) agonists have emerged as therapeutic agents for obesity in adults and have shown benefits outside of weight loss. Here we explore the evidence for GLP-1R agonist use in pediatric obesity. Emerging evidence suggests that GLP-1R agonists have a role in pediatric obesity treatment. A recently published, randomized, placebo-controlled trial found a greater reduction in BMI z-score (− 0.22 SDs) in adolescents receiving liraglutide compared with placebo. As in adults, gastrointestinal adverse effects were commonly seen. GLP-1R agonists appear to perform favorably compared with other approved pharmacological agents for pediatric obesity. However, heterogeneity in weight loss response, cost, side effects, and need for injections may limit their use in many pediatric patients. Rather than broadly applying this therapy if it is approved, we suggest careful patient selection and monitoring by clinicians pending further studies.

Obesity is one of the major life style disorders which may lead to undesirable effects on cholesterol, triglycerides, blood pressure and insulin resistance and eventually increases the risk of various adverse conditions like ischemic heart disease, stroke, coronary artery disease & type 2 diabetes. The present investigation was undertaken to explore protective effects of aerial parts of Fagonia cretica L. extract in cafeteria diet induced obesity in Wistar rats. Female Wistar rats were provided with cafeteria diet (CD) for the period of 10 weeks to induce obesity. Fagonia cretica L. methanolic extracts (200 & 400 mg/kg) & standard drug orlistat (30 mg/kg) were administered for last 6 weeks along with the continuation of CD. Various primary metabolic indicators of obesity like daily food consumption, body weight, lipid profile, fecal fat content & fat pads were studied. Administration of methanolic extract of Fagonia cretica L. significantly stopped increase in daily food consumption & body weight gain as compared to obese control group. Improvement in lipid profile was also observed in the all treatment groups rats as compared to obese control group rats. Obtained results validate that supplementation of Fagonia cretica L. methanolic extracts in obese rats resulted in significant protection against various indicators of obesity.

Obesity, as defined by WHO is an abnormal or excessive fat accumulation that may impair health. is directly proportional to the resultant impact of genetic, metabolic, environment, and culture issues. The leading cause of obesity is an energy imbalance between calories consumed and calories exhausted. To design and optimize SNEDDS formulation by the development of SNEDDS with an appropriate quantity of oil, and with the factorial approach. A series of SNEDDS formulations for was prepared based on solubility studies, pseudo ternary phase diagram and visual observation. was added inaccurately weighed amount of oil into a screw-capped glass vial and heated in a water bath at 40ºC. The and were added to the oily mixture and stirred with a magnetic bar. The formulation was further for 15 minutes and stored at room temperature. From the result of evaluation parameters such as emulsification time 6±1s, % transmittance 94.01±1.5%, drug Loading 99.89%±0.56%, Index 0.47±0.01 and 0.211±0.02, Globulesize99±6 nm, Zeta potential -28.12 and -24.5 , The , Freeze-thaw cycle, Heating-cooling cycle showed no signs of phase separation, Viscosity 132.4±0m Pa.s, drug release 99.25% within 90 minutes, drug release follows Korsmeyer-Peppas model mechanism, n value was found to be1.083 hence it can be postulated formulation F-6 followed the or anomalous release and P-value for factors emulsification time, % transmittance and % drug release was found less than 0.0500 and hence it was concluded formulation F-6 an optimized formulation.

Fat malabsorption associated with Roux-en-Y gastric bypass (RYGB) may contribute to elevated postprandial glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) after the procedure, leading to sustained weight loss and appetite reduction. This study investigated whether fat malabsorption via orlistat increases GLP-1 and PYY and if these increases would be proportional to changes in hunger and satiety. Five healthy participants received standardized meals with 120 mg orlistat or placebo in a randomized, double-blinded, crossover design for 3 days. On the final day, glucose, insulin, GLP-1, PYY3-36 and visual analogue scores for hunger and satiety were measured over a 14-hour period that included three meals. Fasting, 14-hour area under the curve (AUC) and meal-related AUC for glucose and insulin were similar, although postprandial increases in peak insulin and glucose were greater with orlistat. PYY3-36 , GLP-1, hunger and satiety were not different. In conclusion, short-term orlistat administration does not enhance postprandial GLP-1 or PYY3-36 or affect hunger or satiety in normal-weight individuals. Furthermore, fat malabsorption from RYGB is unlikely to mediate subsequent postprandial increases in GLP-1 and PYY.

Purpose : Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis are two forms of fatty liver disease with benign and malignant nature, respectively. These two conditions can cause an increased risk of liver cirrhosis and hepatocellular carcinoma. Given the importance and high prevalence of NAFLD, it is necessary to investigate the results of different studies in related scope to provide a clarity guarantee of effectiveness. Therefore, this systematic review and metaanalysis aim to study the efficacy of various medications used in the treatment of NAFLD. Methods: A systematic search of medical databases identified 1963 articles. After exclusion of duplicated articles and those which did not meet our inclusion criteria, eta-analysis was performed on 84 articles. Serum levels of alanine aminotransferase (ALT), aspartate amino transferase (AST) were set as primary outcomes and body mass index (BMI), hepatic steatosis, and NAFLD activity score (NAS) were determined as secondary outcomes. Results: Based on the P-score of the therapeutic effects on the non-alcoholic steatohepatitis (NASH), we observed the highest efficacy for atorvastatin, tryptophan, orlistat, omega-3 and obeticholic acid for reduction of ALT, AST, BMI, steatosis and NAS respectively. Conclusion: This meta-analysis showed that atorvastatin. life-style modification, weight loss, and BMI reduction had a remarkable effect on NAFLD-patients by decreasing aminotransferases.

This study aimed to investigate the mechanism of rice bran oil on altering lipid absorption and blood lipid level in normal rat. Male Sprague Dawley rat age 3 months old, weighted 250–300 g were grouped into three groups: control (aquabidest 1 ml), orlistat (2.16 mg / 200 g body weight), and rice bran oil (1.04 mg γ-oryzanol / 200 g body weight). The intervention was given through oral gavage, daily for 28 days. Indicators observed were growth performance, total cholesterol and serum triglyceride levels, lipid levels in feces, and accumulation of intra-abdominal fat. The results showed that the treatment did not significantly affect body weight gain. Fecal lipid levels of orlistat, rice bran oil and control group respectively were 0.19g; 0.17g and 0.13 g (p 0.05). The intervention of rice bran oil was shown to reduce blood cholesterol and triglyceride levels in normal mice and did not accumulate intra-abdominal fat. The results suggest that rice bran oil might have an effect on blood lipid regulation but not by preventing lipid absorption.

Introduction: Obesity shows a multifactorial disease and presents a serious public health problem, with an alarming epidemic character. According to NHANES (National Health and Nutrition Examination Survey) from 2015 to 2016, 39.6% of American adults and 18.5% of young people were obese and 7.7% of adults and 5.6% of young people had severe obesity. Brazil ranks fifth in the world ranking, with about 18 million people reaching up to 70 million overweight individuals. Despite shortterm weight loss with diet and exercise, weight regain continues to be a concern. Anti-obesity drugs, such as Sibutramine (SIB), Phentermine (PHEN), Fenproporex (FEN), Mazindol (MAZ), Amfepramone (AMFE) and Orlistat (ORL) may play a role in weight reduction in patients whose condition is refractory to non- and maintenance of weight loss. Objective: A systematic review followed by meta-analysis of randomized clinical trials over the past five years to explore the efficacy and safety of anorexigenic drugs for weight reduction and consequent treatment of obesity. Methods: The search strategy in MEDLINE / Pubmed, Web of Science, ScienceDirect Journals (Elsevier), Scopus (Elsevier), OneFile (Gale) is as follows : - search for mesh terms (Sibutramine, Phentermine, Fenproporex, Mazindol, Amfepramone , Orlistat, Weight loss, Safety), and the use of booleans "and" between mesh terms and "or" among historical findings. Results: It was observed that in the last five years of randomized studies no significant general complications were found, with only 5.7%. The mean overall weight loss was 6.18 (± 2.8) kg in the mean time of 12 months. The overall success rate among these drugs was 80.18%. The p-value values did not present a significant statistical difference, being p Conclusion: The scientific findings of randomized studies on the use of anorexigenic drugs to treat obesity have shown safety and efficiency in the last five years, with a reasonable weight loss and no significant complications.

Objectives: To study the stress degradation behavior of an orlistat by UV spectrophotometric method. Methods: An accurate, simple and rapid UV spectrophotometric method for orlistat was developed and used in phosphate buffer pH 8. The method is validated for linearity, precision and accuracy. Stress degradation study was performed at alkaline, acid, neutral and photolytic conditions. Results: Linearity was found to be 8-28μg/ml. Absorbance showed at different concentrations was found to be linear with the correlation coefficient 0.999. The Intra-day and Inter-day precision studies were carried out. The relative standard deviation was found to be 0.0029 and 0.0095 for Intra-day and Inter-day precision studies respectively. Orlistat was found to be degraded in acidic, alkaline, neutral and oxidative stress conditions whereas it was found to be stable in light. The LOD and LOQ of the developed method were found to be 0.3444μg/ml and 1.0740μg/ ml respectively. Accuracy was studied by the recovery method. Percentage accuracy was found to be 96.19% ± 0.99%. The decrease in absorbance was observed at 1h, which concludes the degradation of the drug in acidic stress conditions. The drug was found to be unstable in alkaline conditions. The results revealed that degradation products are having more absorbance than the drug. The 5 is slight decrease in absorbance was observed at 1h, which remained constant after 4 h. also method showed its usefulness in analyzing marketed samples of orlistat formulations. Conclusion: From the obtained results, it can be concluded that the developed method is simple and economic. It can be successfully used for the stress degradation studies; hence, it can be applied for routine analysis in the industry. Key words: Orlistat, Stress degradation, UV spectrophotometry.

Thevetia peruviana has been used in Mexican traditional medicine for its slimming effects. Active fractions and compounds from T. peruviana were isolated and identified by means of gravitational open-column chromatography, and the fractions were evaluated on mice with MonoSodium Glutamate-induced obesity. Orlistat was used as positive control, and treatments were administered, orally, once a day for 8 weeks. The fraction with higher activity was sub-fractioned and, with the intention of avoiding using more mice, the fractions were analyzed by evaluating their capability to inhibit adipogenesis in the 3T3-L1 cell line. Animals treated with the F-B fraction revealed a significantly smaller weight increase and maintained adequate insulin sensitivity, and significantly lower blood levels of cholesterol and triglycerides. The active compounds that demonstrated greatest adipogenesis inhibition were palmitic acid (1), oleic acid (2), octadecanoic acid (3), 2-palmitoyl glycerol (4), 2-oleoyl glycerol (5) and stigmastenone (6).

Background: Obesity is a rapidly growing concern worldwide, with over one-third of the global population classified as overweight or obese. While significant research has focused on developing new and improved nutritional and dietary approaches for regulating energy intake, there has been little success in overcoming the rising obesity statistics. Consequently, increasing attention is being afforded to designing safe, inexpensive and highly efficacious food-based materials that control fat and carbohydrate bioavailability in order to successfully manage the nutritional value of our food and combat chronic diseases associated with obesity, such as heart disease and diabetes.Scope & approach: This review focuses on bioactive and nanostructured materials that have been shown to regulate energy intake by (i) manipulating the fat digestion process, and/or (ii) restricting the absorption of fat digestion products into the systemic bloodstream. The mechanistic approach of such technologies will be discussed in detail, with corresponding preclinical and clinical findings highlighted, to provide insights for the design and development of future anti-obesity therapeutics.Key findings & conclusions: Bioactive materials that regulate the fat digestion and absorption process have revealed promising preclinical and clinical findings with respects to modulating calorie intake and thus, weight gain. Insights derived from this review suggest materials that adsorb fat/fat digestion products, rather than interfering with enzyme action, are the most promising therapies, due to their ability to overcome the adverse effects associated with or list at (the only FDA approved anti-obesity therapy with a localized mechanism of action within the gastrointestinal tract). Refereed/Peer-reviewed

Obesity is a serious and growing worldwide health challenge associated with type 2 diabetes mellitus, cardiovascular disease, osteoarthritis, some cancers, sleep apnea, asthma, and nonalcoholic fatty liver. The Korean Society for the Study of Obesity recommends that pharmacotherapy should be considered when intensive lifestyle modifications fail to achieve a weight reduction in obese patients with a body mass index ≥25 kg/m2. Long-term medications for obesity have traditionally fallen into two major categories: centrally acting anorexiant medications and peripherally acting medications, such as orlistat. In this paper, we provide an overview of the anti-obesity medications currently available for the long-term and individualized treatment of obesity.

BACKGROUND An association between bariatric surgery and development of de-novo inflammatory bowel disease (IBD) has been observed. AIM To evaluate further the association among bariatric surgery, weight loss medications, obesity and new-onset IBD. METHODS Using Explorys, a population-based Health Insurance Portability and Accountability Act compliant database, we estimated the prevalence of de-novo IBD among patients treated with bariatric surgery (Roux-en-Y gastrojejunostomy, laparoscopic sleeve gastrectomy or gastric banding) (n = 60 870) or weight loss medications (orlistat, phentermine/topiramate, lorcaserin, bupropion/naltrexone and liraglutide) (n = 193 790) compared with obese controls (n = 5 021 210), between 1999 and 2018. RESULTS The prevalence of de-novo IBD was lower among obese patients exposed to bariatric surgery (7.72 per 1000 patients) or weight loss medications (7.22 per 1000 patients) compared with patients with persistent obesity not exposed to these interventions (11.66 per 1000 patients, P < 0.0001). The risk reduction for de-novo IBD was consistent across bariatric surgeries and weight loss medications with the exception of orlistat which was not associated with a reduction in risk for de-novo IBD compared with the persistent obese control cohort. CONCLUSION Obese patients undergoing treatment with bariatric surgery or weight loss medications are at a lower risk for developing de-novo IBD compared with persistently obese controls not exposed to these interventions. These data suggest that obesity and ineffective management of obesity are risk factors for de-novo IBD. Further research is needed to confirm these observations and understand potential mechanisms.

Nowadays obesity is the major health problem due to food habit and life style of people. Nature and natural compounds possess lots of health benefits. To explore the therapeutic benefit of Cyperus rotundus in this work, we have evaluated the anti-obesity potential on Monosodium glutamate (MSG) induced obese rats. Methanolic extract of tubers of Cyperus rotundus was administered at the dose of 250 and 500 mg/kg/oral after 45 d of treatment and a significant improvement in body weight, organs and lipid profile was observed as compared with MSG induced obese rats. Nowadays obesity is a common metabolic disorder in developed and developing countries. It was observed that Cyperus rotundus tuber possesses anti-obesity potential and protective action on heart and liver.

Summary Background The Food and Drug Administration has approved several pharmacotherapies for the treatment of obesity. This study assesses the cost‐effectiveness of six pharmacotherapies and lifestyle intervention for people with mild obesity (body mass indices [BMIs] 30 to 35). Methods A microsimulation model was constructed to compare seven weight loss strategies plus no treatment: intensive lifestyle intervention, orlistat, phentermine, phentermine/topiramate, lorcaserin, liraglutide, and semaglutide. Weight loss, quality‐of‐life scores, and costs were estimated using clinical trials and other published literature. Endpoints included costs, quality‐adjusted life years (QALYs), and incremental cost‐effectiveness ratios (ICERs) with a willingness‐to‐pay (WTP) threshold of $100 000/QALY. Results were analysed at 1‐, 3‐, and 5‐year time horizons. Results At each of the three follow‐up periods, phentermine was the cost‐effective strategy, with ICERs of $46 258/QALY, $20 157/QALY, and $17 880/QALY after 1, 3, and 5 years, respectively. Semaglutide was the most effective strategy in the 3‐ and 5‐year time horizons, with total QALYs of 2.224 and 3.711, respectively. However, the ICERs were prohibitively high at $1 437 340/QALY after 3 years and $576 931/QALY after 5 years. Deterministic and probabilistic sensitivity analyses indicated these results were robust. Conclusions Phentermine is the cost‐effective pharmacologic weight‐loss strategy. Although semaglutide is the most effective, it is not cost‐effective because of its high price.