-
Obesity Surgery Mar 2024Many individuals search for obesity treatment options on the Internet. We aimed to analyze the popularity of pharmacological and surgical obesity treatment methods...
PURPOSE
Many individuals search for obesity treatment options on the Internet. We aimed to analyze the popularity of pharmacological and surgical obesity treatment methods searched by Google users.
MATERIAL AND METHODS
We used Google Trends to identify topics representing the following: recommended surgical methods (n = 9), recommended pharmacological methods (n = 10), and not recommended pharmacological methods (n = 34). The data was generated for 2004-2022 and 2020-2022. Relative search volume (RSV) was adjusted using "Gastric bypass surgery" as a benchmark. We analyzed the geographical and temporal trends of the topics.
RESULTS
In 2004-2022, the topics representing recommended surgical methods numerically gained the most popularity among Google users, but in 2020-2022 the recommended drugs exceeded other obesity treatment methods. The most popular individual topics since 2004 were "flaxseed," "Spirulina," "Carnitine," "Bariatric surgery," and "Orlistat." The most dynamic increases of searches since 2004 were observed for "Sleeve gastrectomy," "Curcumin," "Psyllium," and "Bupropion/Naltrexon." Since 2018, topics representing GLP-1 analogs such as "Semaglutide" and "Saxenda" revealed exponential increases in RSV, causing that "Semaglutide" to become the fourth most popular topic in 2020-2022.
CONCLUSIONS
Google users across the world were the most interested in topics representing bariatric surgery, but recently recommended drugs for the treatment of obesity gained the most attention. The most popular individual topics were dietary supplements with uncertain effects on weight loss.
Topics: Humans; Obesity, Morbid; Search Engine; Retrospective Studies; Obesity; Bariatric Surgery
PubMed: 38103152
DOI: 10.1007/s11695-023-06971-y -
Frontiers in Endocrinology 2023Pharmacological therapy is recommended as a second-line alternative to reverse obesity. Currently, five anti-obesity drugs (AODs) have been approved by the U.S. Food and...
INTRODUCTION
Pharmacological therapy is recommended as a second-line alternative to reverse obesity. Currently, five anti-obesity drugs (AODs) have been approved by the U.S. Food and Drug Administration (FDA) for chronic weight management. The aim of this paper is to investigate the pharmacoeconomic evaluation of AODs through a systematic review with a special focus on methodological considerations.
METHODS
We searched the general and specific databases to identify the primary pharmacoeconomic evaluation of AODs.
RESULTS
A total of 18 full-text articles and three conference abstracts were included in this review. Most of the economic assessments were still about Orlistat. And the observations we could make were consistent with the previous systematic review. A few studies were on the combined therapies (i.e. PHEN/TPM ER and NB ER) compared to different comparators, which could hardly lead to a generalized summary of the cost-effectiveness. Most recently, pharmacoeconomic evidence on the newest GLP 1 RA approved for the indication of obesity or obesity with at least one comorbidity emerged gradually. Modelling-based cost-utility analysis is the major type of assessment method. In the modelling studies, a manageable number of the key health states and the state transitions were structured to capture the disease progression. In particular, the principal structure of the decision model adopted in the three studies on the newly approved drug was nearly the same, which enables more in-depth comparisons and generalizations of the findings.
CONCLUSION
This study provided an up-to-date overview of the strengths and areas for improvement in the methodological design of the pharmacoeconomic evaluation of the licensed drugs for chronic weight management. Future modelling evaluations would benefit from a better understanding of the long-term weight loss effects of the current therapeutic options and the weight rebound process after the discontinuation of treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022302648, identifier CRD42022302648.
Topics: United States; Humans; Anti-Obesity Agents; Economics, Pharmaceutical; Obesity; Orlistat; Comorbidity
PubMed: 38027186
DOI: 10.3389/fendo.2023.1254398 -
Journal of Traditional and... Nov 2023Xianglian Wan (XLW) as a classic prescription of traditional Chinese medicine protects digestive function; however, few studies have investigated its anti-colorectal...
BACKGROUND AND AIM
Xianglian Wan (XLW) as a classic prescription of traditional Chinese medicine protects digestive function; however, few studies have investigated its anti-colorectal cancer effects. This study verified that the effective monomer berberine of XLW plays an antitumo r role by regulating the acetyl-CoA carboxylase (ACC)/fatty acid synthase (FASN) lipid metabolism-related signaling pathway.
EXPERIMENTAL PROCEDURE
The connection between XLW and FASN was identified through literature mining, bioinformatics and structural biology. In vivo experiments verified the rationality of the antitumor effect of berberine by regulating the ACC/FASN pathway, and in vitro experiments verified the regulatory relationship between berberine and FASN.
RESULTS AND CONCLUSION
The most frequent Chinese medicine component in XLW was . Berberine, the active ingredient of XLW, has a FASN binding site. FASN expression is higher in tumor tissues than in normal tissues. FASN is related to colorectal adenocarcinoma occurrence and patient survival time. Experiments showed that XLW, berberine and orlistat (FASN inhibitor) can cooperate with palmitic acid (PA) to inhibit tumors in mice. Berberine can downregulate FASN and ACC expression in tumor tissues and inhibit the increase in acetyl-CoA, the intermediate product of exogenous PA intake. The mechanism by which berberine inhibits colon cancer cell proliferation by lowering lipids is related to its downregulation of FASN protein expression. The ACC/FASN signaling pathway is a critical pathway through which berberine, the effective monomer of XLW, plays an antitumor role in colon cancer.
PubMed: 38020547
DOI: 10.1016/j.jtcme.2023.05.008 -
Journal For Immunotherapy of Cancer Nov 2023Single-cell RNA sequencing, also known as scRNA-seq, is a method profiling cell populations on an individual cell basis. It is particularly useful for more deeply...
BACKGROUND
Single-cell RNA sequencing, also known as scRNA-seq, is a method profiling cell populations on an individual cell basis. It is particularly useful for more deeply understanding cell behavior in a complicated tumor microenvironment. Although several previous studies have examined scRNA-seq for hepatocellular carcinoma (HCC) tissues, no one has tested and analyzed HCC with different stages.
METHODS
In this investigation, immune cells isolated from surrounding normal tissues and cancer tissues from 3 II-stage and 4 III-stage HCC cases were subjected to deep scRNA-seq. The analysis included 15 samples. We distinguished developmentally relevant trajectories, unique immune cell subtypes, and enriched pathways regarding differential genes. Western blot and co-immunoprecipitation were performed to demonstrate the interaction between fatty acid binding protein 1 (FABP1) and peroxisome proliferator-activated receptor gamma(PPARG). In vivo experiments were performed in a C57BL/6 mouse model of HCC established via subcutaneous injection.
RESULTS
FABP1 was discovered to be overexpressed in tumor-associated macrophages (TAMs) with III-stage HCC tissues compared with II-stage HCC tissues. This finding was fully supported by immunofluorescence detection in significant amounts of HCC human samples. FABP1 deficiency in TAMs inhibited HCC progression in vitro. Mechanistically, FABP1 interacted with PPARG/CD36 in TAMs to increase fatty acid oxidation in HCC. When compared with C57BL/6 mice of the wild type, tumors in FABP1-/- mice consistently showed attenuation. The FABP1-/- group's relative proportion of regulatory T cells and natural killer cells showed a downward trend, while dendritic cells, M1 macrophages, and B cells showed an upward trend, according to the results of mass cytometry. In further clinical translation, we found that orlistat significantly inhibited FABP1 activity, while the combination of anti-programmed cell death 1(PD-1) could synergistically treat HCC progression. Liposomes loaded with orlistat and connected with IR780 probe could further enhance the therapeutic effect of orlistat and visualize drug metabolism in vivo.
CONCLUSIONS
ScRNA-seq atlas revealed an FABP1-dependent immunosuppressive environment in HCC. Orlistat significantly inhibited FABP1 activity, while the combination of anti-PD-1 could synergistically treat HCC progression. This study identified new treatment targets and strategies for HCC progression, contributing to patients with advanced HCC from new perspectives.
Topics: Animals; Humans; Mice; Carcinoma, Hepatocellular; Fatty Acid-Binding Proteins; Immunosuppressive Agents; Liver Neoplasms; Mice, Inbred C57BL; Orlistat; PPAR gamma; RNA; Tumor Microenvironment
PubMed: 38007237
DOI: 10.1136/jitc-2023-007030 -
Molecules (Basel, Switzerland) Oct 2023has been not only used as a heat-clearing and detoxicating functional tea (Ku-Ding-Cha) but also consumed as a hypotensive, anti-diabetic, and weight-reducing folk...
has been not only used as a heat-clearing and detoxicating functional tea (Ku-Ding-Cha) but also consumed as a hypotensive, anti-diabetic, and weight-reducing folk medicine. From the leaves of , ten new monoterpenoid glycosides named ligurobustosides T (), T (), T (), T (), T (), T (), F (), T (), T (), and E (), together with five known ones (, , , , ), were separated and identified using the spectroscopic method and chemical method in this research. The results of biological tests exhibited that the fatty acid synthase (FAS) inhibitory action of compound (IC: 4.38 ± 0.11 μM) was as strong as orlistat (IC: 4.46 ± 0.13 μM), a positive control; the α-glucosidase inhibitory actions of compounds - and -, and the α-amylase inhibitory actions of compounds - were medium; the ABTS radical scavenging capacities of compounds - and - (IC: 6.27 ± 0.23 ~ 8.59 ± 0.09 μM) were stronger than l-(+)-ascorbic acid (IC: 10.06 ± 0.19 μM) served as a positive control. This research offered a theoretical foundation for the leaves of to prevent diabetes and its complications.
Topics: Ligustrum; Glycosides
PubMed: 37959693
DOI: 10.3390/molecules28217274 -
Foods (Basel, Switzerland) Oct 2023Black garlic, also known as fermented garlic, is a useful food that may have therapeutic benefits. The aim of this study was to analyze the impact of fermented garlic...
BACKGROUND
Black garlic, also known as fermented garlic, is a useful food that may have therapeutic benefits. The aim of this study was to analyze the impact of fermented garlic and orlistat therapy on obese rats.
METHODS
A total of 40 male albino rats (245-250 g) were fed either an HFD ( = 32) or a normal diet ( = 8) for 6 weeks; therefore we randomly assigned the rats into: group I (normal diet), group II (HFD), groups III and IV (HFD with fermented garlic), and group V (orlistat for) 6 weeks. Two different dosages of fermented garlic (481.2 mg/kg and 963.3 mg/kg) were administered. Afterward, blood was collected, body weight was measured, and tissue was collected for further analysis.
RESULTS
Both the orlistat and black garlic groups showed a significant reduction in BMI, lipid profiles, and insulin levels compared with the baseline. The orlistat group showed significant elevation ( < 0.005) in body weight, organ weight, lipids, and liver parameters, with histopathological findings. The administration of black garlic improved the inflammatory markers with all other parameters.
CONCLUSION
The fermented garlic and orlistat reinstated all of the investigated parameters significantly ( < 0.05), especially body weight and lipid profiles, and induced histopathological changes compared to the drug orlistat. Additionally, it showed anti-obesity-related therapeutic impacts compared with the orlistat drug. Black garlic provides a reliable and effective treatment for obesity compared to orlistat.
PubMed: 37959027
DOI: 10.3390/foods12213905 -
European Journal of Pharmaceutical... Jan 2024Enabling formulations, such as lipid-based formulations (LBFs), are means to deliver challenging-to-formulate, poorly soluble drugs. LBFs may be composed of lipids,...
Enabling formulations, such as lipid-based formulations (LBFs), are means to deliver challenging-to-formulate, poorly soluble drugs. LBFs may be composed of lipids, surfactants and/or cosolvents and can be classified depending on the proportions of the components and the hydrophilicity of the surfactant according to the Lipid Formulations Classification System, ranging from type I (very lipophilic) to type IV (hydrophilic). In cases where drug solubility in LBFs does not suffice, e.g. for preclinical toxicity studies, supersaturated LBFs can be used in order to increase the drug load. However, the effect of digestion on drug absorption from supersaturated type I formulations (consisting exclusively of lipids) still remains relatively unexplored and unclear. In the present study, the impact of lipid digestion on absorption of cinnarizine-loaded supersaturated lipid-based formulations of type I was investigated in rats by pre-dosing of the lipase inhibitor orlistat. The lipid chain length and the drug dose were varied by testing medium-chain triglycerides (MCT) and long-chain triglycerides (LCT), both supersaturated and non-supersaturated. Due to the physical instability of supersaturated formulations of cinnarizine, i.e. a potential of precipitation of cinnarizine, the impact of the addition of the amphiphilic polymer Soluplus®, as a potential precipitation inhibitor, was also investigated. The supersaturated systems resulted in a 2.3 - 3.3-fold higher Area Under the Curve (AUC, not dose-normalized) and 1.4 - 2.2-fold higher maximum plasma concentration (C, not dose-normalized) than non-supersaturated formulations (statistically significant with p = 0.05), whereas the addition of Soluplus® did not reveal any benefit. Results indicated that lipase inhibition affected the in vivo performance of LBFs: Co-administration of the lipase inhibitor significantly reduced C and AUC (both to 33-39 %, not dose-normalized) for the LCT formulations and, though not significant, a similar trend was observed for the AUC of the MCT formulations (to 53-87 %), suggesting a higher dependency on lipolysis for LCT. Also, t tended to decrease to 20-60 % when compared to the animals not dosed with orlistat but lacking statistical significance. Without lipase inhibition, the LCT in general lead to better absorption of cinnarizine as compared to MCT, with 1.2-1.7-fold higher AUC and 1.4-1.8-fold higher C, but without showing statistical significance. Overall, the study revealed that lipolysis plays a major role in drug absorption from supersaturated lipid-based formulations type I.
Topics: Rats; Animals; Cinnarizine; Orlistat; Pharmaceutical Preparations; Triglycerides; Solubility; Surface-Active Agents; Lipase; Digestion; Administration, Oral
PubMed: 37951315
DOI: 10.1016/j.ejps.2023.106634 -
BMC Complementary Medicine and Therapies Oct 2023Obesity is a global health issue arising from the unhealthy accumulation of fat. Medicinal plants such as Alstonia boonei stem bark has been reported to possess body...
BACKGROUND
Obesity is a global health issue arising from the unhealthy accumulation of fat. Medicinal plants such as Alstonia boonei stem bark has been reported to possess body weight reducing effect in obese rats. Thus, this study sought to investigate the in vitro and in silico effects of fractions from Alstonia boonei stem bark on selected obesity-related digestive enzymes and adipogenesis in 3T3-L1 preadipocytes.
METHOD
Two fractions were prepared from A. boonei: crude alkaloid fraction (CAF) and crude saponin fraction (CSF), and their phytochemical compounds were profiled using Liquid chromatography with tandem mass spectrometry (LCMS/MS). The fractions were assayed for inhibitory activity against lipase, α-amylase and α-glucosidase, likewise their antiadipogenic effect in 3T3-L1 adipocytes. The binding properties with the 3 enzymes were also assessed using in silico tools.
RESULTS
Eleven alkaloids and six saponin phytochemical compounds were identified in the CAF and CSF using LCMS/MS. The CAF and CSF revealed good inhibitory activity against pancreatic lipase enzyme, but weak and good activity against amylase respectively while only CSF had inhibitory activity against α-glucosidase. Both fractions showed antiadipogenic effect in the clearance of adipocytes and reduction of lipid content in 3T3-L1 adipocytes. The LCMS/MS identified compounds (41) from both fractions demonstrated good binding properties with the 3 enzymes, with at least the top ten compounds having higher binding energies than the reference inhibitors (acarbose and orlistat). The best two docked compounds to the three enzymes were firmly anchored in the substrate binding pockets of the enzymes. In a similar binding pattern as the reference acarbose, Estradiol-17-phenylpropionate (-11.0 kcal/mol) and 3α-O-trans-Feruloyl-2 α -hydroxy-12-ursen-28-oic acid (-10.0 kcal/mol) interacted with Asp197 a catalytic nucleophile of pancreatic amylase. Estradiol-17-phenylpropionate (-10.8 kcal/mol) and 10-Hydroxyyohimbine (-10.4 kcal/mol) interacted with the catalytic triad (Ser152-Asp176-His263) of pancreatic lipase while Estradiol-17-phenylpropionate (-10.1 kcal/mol) and 10-Hydroxyyohimbine (-9.9 kcal/mol) interacted with Asp616 and Asp518 the acid/base and nucleophilic residues of modelled α-glucosidase.
CONCLUSION
The antiobesity effect of A. boonei was displayed by both the alkaloid and saponin fractions of the plant via inhibition of pancreatic lipase and adipogenesis.
Topics: Mice; Rats; Animals; Adipogenesis; Plant Extracts; Alstonia; 3T3-L1 Cells; Acarbose; alpha-Glucosidases; Plant Bark; Obesity; Lipase; Alkaloids; Amylases; Saponins
PubMed: 37864233
DOI: 10.1186/s12906-023-04202-6 -
JAMA Network Open Oct 2023Although the American Academy of Pediatrics has recommended treatment with antiobesity drugs for adolescents, the cost-effectiveness of antiobesity drugs for this...
IMPORTANCE
Although the American Academy of Pediatrics has recommended treatment with antiobesity drugs for adolescents, the cost-effectiveness of antiobesity drugs for this population is still unknown.
OBJECTIVE
To quantify cost-effectiveness of different antiobesity drugs available for pediatric use.
DESIGN, SETTING, AND PARTICIPANTS
This economic evaluation used a Markov microsimulation model with health states defined by obesity levels. Effectiveness was measured by quality-adjusted life-years (QALYs) and costs were calculated from third-party payer perspective, estimated in 2023 US dollars over a 10-year horizon. Data were obtained from the published literature.
INTERVENTION
Antiobesity drugs orlistat, liraglutide, semaglutide, and phentermine-topiramate vs no treatment. Metformin hydrochloride and 2 types of bariatric surgical procedures (sleeve gastrectomy and gastric bypass) were considered in sensitivity analysis.
MAIN OUTCOMES AND MEASURES
Incremental cost-effectiveness ratio.
RESULTS
Among the 4 antiobesity drugs currently approved for pediatric use, phentermine-topiramate was the most cost-effective with an incremental cost-effectiveness ratio of $93 620 per QALY relative to no treatment in this simulated cohort of 10 000 adolescents aged 12 to 17 years (mode, 15 years) with severe obesity (62% female). While semaglutide offered more QALYs than phentermine-topiramate, its higher cost resulted in an incremental cost-effectiveness ratio ($1 079 480/QALY) that exceeded the commonly used willingness-to-pay threshold of $100 000 to $150 000/QALY. Orlistat and liraglutide cost more and were less effective than phentermine-topiramate and semaglutide, respectively. Sleeve gastrectomy and gastric bypass were more effective than phentermine-topiramate but were also more costly, rendering them not cost-effective compared with phentermine-topiramate at the willingness-to-pay threshold of $100 000 to $150 000/QALY.
CONCLUSIONS AND RELEVANCE
In this economic evaluation of weight loss drugs for adolescents with severe obesity, we found phentermine-topiramate to be a cost-effective treatment at a willingness-to-pay threshold of $100 000 to $150 000/QALY. Further research is needed to determine long-term drug efficacy and how long adolescents continue treatment.
Topics: Humans; Female; Adolescent; Child; Male; Anti-Obesity Agents; Obesity, Morbid; Cost-Benefit Analysis; Orlistat; Topiramate; Liraglutide; Obesity; Phentermine
PubMed: 37824146
DOI: 10.1001/jamanetworkopen.2023.36400 -
Romanian Journal of Internal Medicine =... Mar 2024Obesity and overweight are the major risk factors for numerous chronic diseases, including cardiovascular diseases such as heart disease and stroke, which are the... (Review)
Review
Obesity and overweight are the major risk factors for numerous chronic diseases, including cardiovascular diseases such as heart disease and stroke, which are the leading causes of death worldwide. The prevalence of obesity has dramatically risen in both developed and developing countries, making it a significant public health concern and a global crisis. Despite lifestyle modifications being the first-line treatment, the high risk of relapse has led to a growing interest in non-invasive pharmacotherapeutic interventions to achieve and maintain weight loss and reverse the growth of the obesity epidemic. Cardiovascular diseases and cancer account for the highest mortality rates among other comorbidities associated with obesity and overweight. Excess and abnormally deposited adipose tissue secretes various inflammatory mediators, leading to cardiovascular diseases and cancers. Weight loss of 5-10% significantly reduces cardiometabolic risk. Medications currently approved in the USA for long-term management of obesity are orlistat, naltrexone, bupropion, phentermine/topiramate, and Glucagon Like Peptide-1 (GLP-1) agonists such as liraglutide and semaglutide. The benefit-to-risk of medications, comorbidities, and individual responses should guide the treatment decisions. The article provides a comprehensive overview and discussion of several weight loss medications used previously and currently, including their efficacy, mechanisms of action, and side effects.
Topics: Humans; Overweight; Cardiovascular Diseases; Obesity; Anti-Obesity Agents; Weight Loss
PubMed: 37752761
DOI: 10.2478/rjim-2023-0023