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The Korean Journal of Gastroenterology... Mar 2024The prevalence of obesity with various complications is increasing rapidly in Korea. Although lifestyle modification is fundamental in obesity treatment, more effective... (Review)
Review
The prevalence of obesity with various complications is increasing rapidly in Korea. Although lifestyle modification is fundamental in obesity treatment, more effective treatment tools are required. Many advances in obesity treatment have been reported recently, including lifestyle modifications and pharmacological, endoscopic, and surgical treatments. Drugs with proven long-term efficacy and safety are preferred because management for obesity treatment is a long-term process. Currently, four medications are available for long-term use in Korea: Orlistat, Naltrexone/bupuropion NR, Phentermine/topiramate capsule, and Liraglutide. Recently, semaglutide and tirzepatide have been attracting attention because of their effectiveness and convenience, but they are not yet available in Korea. In addition, there are limitations such as the yo-yo effect when discontinuing the drug, long-term safety, and cost. Patients and medical staff must be aware of the advantages and side effects of each medication to ensure the successful treatment of obesity.
Topics: Humans; Anti-Obesity Agents; Phentermine; Obesity; Orlistat; Liraglutide
PubMed: 38522852
DOI: 10.4166/kjg.2024.016 -
Frontiers in Pharmacology 2024Artemisia dracunculus: L. () is a popular vegetable and spice cultivated across many Middle Eastern countries. The herb's aqueous extract has significant folkloric...
Artemisia dracunculus: L. () is a popular vegetable and spice cultivated across many Middle Eastern countries. The herb's aqueous extract has significant folkloric medicinal importance for treating various disorders. Hence, the present investigation aimed to investigate hydrophilic extract phytochemical constituents and pleiotropic biological potentials, as no previous studies have investigated the antilipase and anti-α-amylase effects of the plant. Total phenol content and phytochemical screening assays were performed utilizing standard analytical methods. While the α-amylase inhibition, free radical-scavenging, antilipase, and cytotoxic activities were determined using dinitrosalicylic acid (DNSA), DPPH, p-nitrophenyl butyrate (PNPB), and MTS assays, respectively. The standard phytochemical analysis of aqueous extract shows that this extract contains only a phenolic group. The total phenol content was 0.146 ± 0.012 mg GAE/g of the plant dry extract. The aqueous extract exhibited potent DPPH free radical inhibitory (IC dose of 10.71 ± 0.01 μg/mL) and anti-lipase activities (IC dose of 60.25 ± 0.33 μg/mL) compared with Trolox (IC = 5.7 ± 0.92 μg/mL) and Orlistat (IC = 12.3 ± 0.35 μg/mL), respectively. However, it showed a weak anti-α-amylase effect (IC value > 1,000 μg/mL) compared with Acarbose (IC = 28.18 ± 1.27 μg/mL). has a cytotoxic effect against the HeLa cancer cell line compared with the chemotherapeutic agent Doxorubicin. The extract has the same percent of inhibition as Doxorubicin (99.9%) at 10 mg/mL. Overall, these results pointed out for the first time the importance of considering effects as a favorite candidate for preventing and treating metabolic disorders. Also, our results confirm the findings of previous reports on the role of in the management of cancer and disorders resulting from the accumulation of harmful free radicals. On the contrary, the current study concluded that the antidiabetic role of could be minimal. Further in-depth investigations are urgently warranted to explore the importance of A. dracunculus in pharmaceutical production.
PubMed: 38515857
DOI: 10.3389/fphar.2024.1351743 -
Journal of the Endocrine Society Mar 2024Despite a high prevalence of obesity in the veteran population, antiobesity medications (AOMs) have been underused in the Veterans Health Administration. Real-world...
CONTEXT
Despite a high prevalence of obesity in the veteran population, antiobesity medications (AOMs) have been underused in the Veterans Health Administration. Real-world reports on outcomes when AOMs have been used in veterans is limited.
OBJECTIVE
To analyze weight loss outcomes from a local Veterans Health Administration pharmacotherapy-based weight management clinic (WMC).
METHODS
This was a retrospective cohort study of veterans enrolled in a local WMC for 15 months from August 2016 through September 2018 and followed through November 2019. Patients were offered 1 of 5 available AOMs based on their comorbidities. Factors associated with weight loss (5% or more weight loss) were assessed.
KEY RESULTS
A total of 159 patients were seen in a WMC, 149 (93.7%) veterans were prescribed an AOM, and 129 returned for follow-up. Overall, 61/129 (47%) patients achieved 5% or greater weight loss and 28/129 (22%) achieved 10% or greater weight loss within 15 months. Clinically significant weight loss (%) over the first 15 months was achieved with phentermine/topiramate ER (-6.3%) and liraglutide (-7.5%), but not with orlistat (-3.9%) and lorcaserin (-3.6%). Comorbid obstructive sleep apnea was negatively associated with achieving ≥5% weight loss.
CONCLUSION
Phentermine/topiramate ER and liraglutide were found to be effective AOMs among veterans. Further work is needed to mitigate barriers to AOM initiation given the continued rise in obesity.
PubMed: 38515583
DOI: 10.1210/jendso/bvae042 -
Obesity Surgery May 2024A significant proportion of patients experience insufficient weight loss or weight regain after bariatric surgery. There is a paucity of literature describing...
PURPOSE
A significant proportion of patients experience insufficient weight loss or weight regain after bariatric surgery. There is a paucity of literature describing anti-obesity medication (AOM) use following bariatric surgery. We sought to identify prevalence and trends of AOM use following bariatric surgery.
MATERIALS AND METHODS
We utilized the IBM Explorys® database to identify all adults with prior bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy). Those prescribed AOMs (semaglutide, liraglutide, topiramate, phentermine/topiramate, naltrexone/bupropion, orlistat) within 5 years of surgery were further identified. Data was analyzed to characterize AOM utilization among different age, demographic, and comorbid populations.
RESULTS
A total of 59,160 adults with prior bariatric surgery were included. Among AOMs studies, prevalence of use was highest for topiramate (8%), followed by liraglutide (2.9%), phentermine/topiramate (1.03%), naltrexone/bupropion (0.95%) semaglutide (0.52%), and orlistat (0.17%). Age distribution varied, with the highest utilization among those age 35-39 years for topiramate, 40-44 years for phentermine/topiramate and naltrexone/bupropion, 45-49 years for semaglutide, and 65-69 years for liraglutide and orlistat. African American race was associated with higher utilization across all AOMs. Among comorbidities, hypertension, hyperlipidemia, and diabetes mellitus were most associated with AOM use.
CONCLUSION
Despite a relatively high incidence of weight regain, AOMs are underutilized following bariatric surgery. It is imperative that barriers to their use be addressed and that AOMs be considered earlier and more frequently in patients with insufficient weight loss or weight regain after bariatric surgery.
Topics: Adult; Humans; Orlistat; Topiramate; Liraglutide; Naltrexone; Bupropion; Obesity, Morbid; Retrospective Studies; Anti-Obesity Agents; Bariatric Surgery; Gastric Bypass; Phentermine; Weight Loss; Weight Gain; Arthritis; Connective Tissue Diseases; Hearing Loss, Sensorineural; Retinal Detachment
PubMed: 38512645
DOI: 10.1007/s11695-024-07181-w -
European Neuropsychopharmacology : the... May 2024The study addresses concerns about potential psychiatric side effects of Glucagon-like peptide-1 receptor agonists (GLP-1 RA).
Exploring the association between suicidal thoughts, self-injury, and GLP-1 receptor agonists in weight loss treatments: Insights from pharmacovigilance measures and unmasking analysis.
INTRODUCTION
The study addresses concerns about potential psychiatric side effects of Glucagon-like peptide-1 receptor agonists (GLP-1 RA).
AIM
The aim of this work was to analyse adverse drug reports (ADRs) from the Food and Drug Administration Adverse Events Reporting System (FAERS) using metformin and orlistat as comparators.
METHODS
Descriptive and pharmacovigilance disproportionality analyses was performed.
RESULTS
A total of 209,354 ADRs were reported, including 59,300 serious cases. Of those, a total of 5378 psychiatric disorder cases, including 383 'serious' cases related to selected ADRs were registered during 2005-2023. After unmasking, 271 cases where individual GLP-1 RA were implicated showing liraglutide (n = 90; Reported Odds Ratio (ROR) = 1.64), exenatide (n = 67; ROR = 0.80), semaglutide (n = 61; ROR = 2.03), dulaglutide (n = 45; ROR = 0.84), tirzepatide (n = 5; ROR = 1.76) and albiglutide (n = 2; ROR = 0.04). A greater association between these ADRs with metformin was observed, but not orlistat. With regards to selected preferred terms (PTs), 42 deaths including 13 completed suicides were recorded. Suicidal ideation was recorded in n = 236 cases for 6/7 GLP-1 RA (excluding lixisenatide).
DISCUSSION
Suicide/self-injury reports pertaining to semaglutide; tirzepatide; and liraglutide were characterised, although lower than metformin. It is postulated that rapid weight loss achieved with GLP-1 RA can trigger significant emotional, biological, and psychological responses, hence possibly impacting on suicidal and self-injurious ideations.
CONCLUSIONS
With the current pharmacovigilance approach, no causality link between suicidal ideation and use of any GLP-1 RA can be inferred. There is a need for further research and vigilance in GLP-1 RA prescribing, particularly in patients with co-existing psychiatric disorders.
Topics: Humans; Glucagon-Like Peptide-1 Receptor; Pharmacovigilance; Male; Female; Suicidal Ideation; Adult; Middle Aged; Self-Injurious Behavior; Anti-Obesity Agents; Adverse Drug Reaction Reporting Systems; Metformin; Weight Loss; Aged; Liraglutide; Orlistat; Hypoglycemic Agents; Exenatide; Young Adult; Glucagon-Like Peptide-1 Receptor Agonists
PubMed: 38508100
DOI: 10.1016/j.euroneuro.2024.02.003 -
BMC Primary Care Mar 2024The prevalence of obesity has been increasing worldwide and is associated with increased risk of morbidity and mortality. Weight management can reduce the risk of...
BACKGROUND
The prevalence of obesity has been increasing worldwide and is associated with increased risk of morbidity and mortality. Weight management can reduce the risk of complications and improve the quality of life of patients with obesity. This study explored primary care physicians' (PCPs') attitudes and knowledge about weight management.
METHODS
An anonymous questionnaire was distributed to 400 PCPs between 2020 and 2021. The survey included questions on treatment approaches (pharmaceutical and surgical) and items regarding the respondents' demographic characteristics. We compared PCPs with low or high proactivity toward weight management. We explored attitudes and knowledge with the chi-square test for categorical variables or the Mann-Whitney test for continuous variables.
RESULTS
A total of 145 PCPs answered our survey (a response rate of 36.25%). More than half (53.8%) of the respondents showed low proactivity toward weight management in their practice. Proactive respondents were more likely to believe that pharmaceutical treatment effectively reduces weight and offered medical and surgical treatment options more frequently to their patients. Lack of knowledge was the most predominant reason for PCPs avoiding offering treatment to their patients, especially in less proactive PCPs (33.3% vs. 5.3%, p-value < 0.001). When comparing different pharmaceutical options, 46.6% of PCPs report they tend to prescribe liraglutide to their patients compared with only 11% who prescribe orlistat and 10.3% who prescribe phentermine (p-value < 0.001).
CONCLUSIONS
Many PCPs still do not actively provide obesity treatment despite improved awareness and therapeutic options. PCPs' proactivity and attitudes are vital to this effort.
Topics: Humans; Cross-Sectional Studies; Physicians, Primary Care; Israel; Quality of Life; Obesity; Pharmaceutical Preparations
PubMed: 38504167
DOI: 10.1186/s12875-024-02324-5 -
ACS Omega Mar 2024Palmitoyl-protein thioesterase 1 (PPT1) is an understudied enzyme that is gaining attention due to its role in the depalmitoylation of several proteins involved in...
Palmitoyl-protein thioesterase 1 (PPT1) is an understudied enzyme that is gaining attention due to its role in the depalmitoylation of several proteins involved in neurodegenerative diseases and cancer. PPT1 is overexpressed in several cancers, specifically cholangiocarcinoma and esophageal cancers. Inhibitors of PPT1 lead to cell death and have been shown to enhance the killing of tumor cells alongside known chemotherapeutics. PPT1 is hence a viable target for anticancer drug development. Furthermore, mutations in PPT1 cause a lysosomal storage disorder called infantile neuronal ceroid lipofuscinosis (CLN1 disease). Molecules that can inhibit, stabilize, or modulate the activity of this target are needed to address these diseases. We used PPT1 enzymatic assays to identify molecules that were subsequently tested by using differential scanning fluorimetry and microscale thermophoresis. Selected compounds were also tested in neuroblastoma cell lines. The resulting PPT1 screening data was used for building machine learning models to help select additional compounds for testing. We discovered two of the most potent PPT1 inhibitors reported to date, orlistat (IC 178.8 nM) and palmostatin B (IC 11.8 nM). When tested in HepG2 cells, it was found that these molecules had decreased activity, indicating that they were likely not penetrating the cells. The combination of in vitro enzymatic and biophysical assays enabled the identification of several molecules that can bind or inhibit PPT1 and may aid in the discovery of modulators or chaperones. The molecules identified could be used as a starting point for further optimization as treatments for other potential therapeutic applications outside CLN1 disease, such as cancer and neurological diseases.
PubMed: 38496939
DOI: 10.1021/acsomega.3c09607 -
Cancer Research Mar 2024Immune checkpoint inhibitors (ICI) transformed the treatment landscape of hepatocellular carcinoma (HCC). Unfortunately, patients with attenuated MHC-I expression remain...
UNLABELLED
Immune checkpoint inhibitors (ICI) transformed the treatment landscape of hepatocellular carcinoma (HCC). Unfortunately, patients with attenuated MHC-I expression remain refractory to ICIs, and druggable targets for upregulating MHC-I are limited. Here, we found that genetic or pharmacologic inhibition of fatty acid synthase (FASN) increased MHC-I levels in HCC cells, promoting antigen presentation and stimulating antigen-specific CD8+ T-cell cytotoxicity. Mechanistically, FASN inhibition reduced palmitoylation of MHC-I that led to its lysosomal degradation. The palmitoyltransferase DHHC3 directly bound MHC-I and negatively regulated MHC-I protein levels. In an orthotopic HCC mouse model, Fasn deficiency enhanced MHC-I levels and promoted cancer cell killing by tumor-infiltrating CD8+ T cells. Moreover, the combination of two different FASN inhibitors, orlistat and TVB-2640, with anti-PD-L1 antibody robustly suppressed tumor growth in vivo. Multiplex IHC of human HCC samples and bioinformatic analysis of The Cancer Genome Atlas data further illustrated that lower expression of FASN was correlated with a higher percentage of cytotoxic CD8+ T cells. The identification of FASN as a negative regulator of MHC-I provides the rationale for combining FASN inhibitors and immunotherapy for treating HCC.
SIGNIFICANCE
Inhibition of FASN increases MHC-I protein levels by suppressing its palmitoylation and lysosomal degradation, which stimulates immune activity against hepatocellular carcinoma and enhances the efficacy of immune checkpoint inhibition.
Topics: Animals; Humans; Mice; B7-H1 Antigen; Carcinoma, Hepatocellular; Cell Line; Fatty Acid Synthase, Type I; Liver Neoplasms; Proteins
PubMed: 38486485
DOI: 10.1158/0008-5472.CAN-23-0966 -
Scientific Reports Mar 2024Mosquitoes are one of the deadliest and most hazardous animals on Earth, where they transmit several diseases that kill millions of people annually. There is an ongoing...
Mosquitoes are one of the deadliest and most hazardous animals on Earth, where they transmit several diseases that kill millions of people annually. There is an ongoing search almost everywhere in the world for more effective and contemporary ways to control mosquitoes other than pesticides. Phytochemicals are affordable, biodegradable biological agents that specialize in eliminating pests that represent a risk to public health. The effectiveness of Acacia nilotica methanol and aqueous leaf extracts against 4th instar larvae was evaluated. The results revealed that the methanol extract of A. nilotica had a noticeable influence on the mortality rate of mosquito larvae, especially at high concentrations. Not only did the mortality rate rise significantly, but the hatching of the mosquito eggs was potentially suppressed.Terpenes, fatty acids, esters, glycosides, pyrrolidine alkane, piperazine, and phenols were the most prevalent components in the methanol extract, while the aqueous extract of A. nilotica exclusively showed the presence of fatty acids. The insecticidal susceptibility tests of both aqueous and alcoholic extract of A. nilotica confirmed that the Acacia plant could serves as a secure and efficient substitute for chemical pesticides because of its promising effect on killing larvae and egg hatching delaying addition to their safety as one of the natural pesticides. Molecular docking study was performed using one of the crucial and life-controlling protein targets, fatty acid binding protein (FABP) and the most active ingredients as testing ligands to describe their binding ability. Most of the structurally related compounds to the co-crystallized ligand, OLA, like hexadecanoic acid furnished high binding affinity to the target protein with very strong and stable intermolecular hydrogen bonding and this is quite similar to OLA itself. Some other structural non-related compounds revealed extraordinarily strong binding abilities like Methoxy phenyl piperazine. Most of the binding reactivities of the majortested structures are due to high structure similarity between the positive control, OLA, and tested compounds. Such structure similarity reinforced with the binding abilities of some detected compounds in the A. nilotica extract could present a reasonable interpretation for its insecticidal activity via deactivating the FABP protein. The FABP4 enzyme inhibition activity was assessed for of both methanolic and aqueous of acacia plant extract and the inhibition results of methanol extract depicted noticeable potency if compared to orlistat, with half-maximal inhibitory concentration (IC) of 0.681, and 0.535 µg/ml, respectively.
Topics: Animals; Humans; Acacia; Molecular Docking Simulation; Methanol; Insecticides; Fatty Acids; Piperazines; Culex
PubMed: 38486053
DOI: 10.1038/s41598-024-56690-2 -
Lipids in Health and Disease Mar 2024Obesity is associated with elevated serum uric acid (SUA) levels and frequent gout flares. Losing weight can reduce the SUA level and gout flares. The effect of orlistat... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Obesity is associated with elevated serum uric acid (SUA) levels and frequent gout flares. Losing weight can reduce the SUA level and gout flares. The effect of orlistat on SUA levels and gout flares in patients with overweight/obesity and hyperuricemia (HUA) has not been extensively studied. This study investigated the effects of orlistat on SUA levels and gout flares compared to placebo in overweight and obese patients with HUA.
METHODS
A total of 72 Chinese patients with overweight/obesity and HUA were randomly divided into a placebo group (35, 48.6%) and an orlistat group (37, 51.4%); the trial lasted 12 weeks. The primary endpoints were the relative changes in body weight, the SUA level, and gout flares in the per-protocol population.
RESULTS
Orlistat reduced the proportion of patients with gout flares (log-rank P = 0.023, hazard ratio = 0.31, 95% confidence interval 0.11-0.85). There was no significant difference in SUA level between the two groups. The average weight loss of the orlistat group was 2.85 kg, and the average weight loss of the placebo group was 0.76 kg. The weight loss in the orlistat group was significantly greater than that in the control group (P < 0.05).
CONCLUSIONS
This study is the first to demonstrate that orlistat has no significant effect on SUA levels in patients with overweight/obesity and HUA. The utility of orlistat as an adjunct therapy to prevent gout flares during weight loss in patients with HUA was emphasized.
TRIAL REGISTRATION
Clinicaltrials.gov NCT05496075.
Topics: Humans; Male; Double-Blind Method; Gout; Hyperuricemia; Obesity; Orlistat; Overweight; Uric Acid; Weight Loss
PubMed: 38468241
DOI: 10.1186/s12944-024-02047-7