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Obesity is a risk factor for the development of noncommunicable diseases that impair the quality of life. Orlistat is one of the most widely used drugs in the management of obesity due to its accessibility and low cost. However, cases of hepatotoxicity have been reported due to the consumption of this drug. On the other hand, piperine is an alkaloid found in black pepper that has demonstrated antiobesity, antihyperlipidemic, antioxidant, prebiotic, and hepatoprotective effects. The aim of this study was to evaluate the protective effect of piperine on the toxicity of orlistat in liver tissue. Obese male rats were administered piperine (30 mg/kg), orlistat (60 mg/kg), and the orlistat‐piperine combination (30 mg/kg + 60 mg/kg) daily for 6 weeks. It was observed that the orlistat‐piperine treatment resulted in greater weight loss, decreased biochemical markers (lipid profile, liver enzymes, pancreatic lipase activity), and histopathological analysis showed decreased hepatic steatosis and reduction of duodenal inflammation. Transcriptomic analysis revealed that the administration of piperine with orlistat increased the expression of genes related to the beta‐oxidation of fatty acids, carbohydrate metabolism, detoxification of xenobiotics, and response to oxidative stress. Therefore, the results suggest that the administration of orlistat‐piperine activates signaling pathways that confer a hepatoprotective effect, reducing the toxic impact of this drug. [ABSTRACT FROM AUTHOR]

High-fat diets have detrimental health impacts that increase the likelihood of developing obesity and metabolic syndrome. This study aimed to examine the potential antioxidant and anti-inflammatory effects of orlistat and white tea in rats fed a high-fat diet. Thirty-two rats were randomized into four groups: control (standard diet), HFD (high-fat diet), HFD+Orlistat (high-fat diet+orlistat), and HFD+WT (high-fat diet+white tea extract). A significant increase in malondialdehyde (MDA) levels and a decrease in total thiol (TT) levels were detected in the HFD group (p < 0.001). On the other hand, a decrease in the MDA level (p < 0.001) and an increase in the TT level were observed in the orlistat and white tea groups compared with those in the HFD group (p < 0.001). Histopathological examinations revealed that, compared with the HFD alone, orlistat and white tea reduced fat accumulation, prevented degenerative changes in hepatocytes, and decreased the histopathological damage score (p = 0.001). Immunohistochemical examinations of nuclear factor-kappa B (NF-kB/p65) revealed that compared with the HFD, orlistat and white tea reduced immunopositivity (p = 0.001). White tea decreases lipid peroxidation and oxidative stress. Both white tea and orlistat decreased fat formation and inflammation in the liver and regulated inflammation by reducing Nf-kB positivity. Nevertheless, further research is needed to assess their impact on human subjects. [ABSTRACT FROM AUTHOR]

Background: The issue of human mental health is gaining more and more attention nowadays. However, most mental disorders are treated with antipsychotic drugs that cause weight gain and metabolic disorders, which include olanzapine (OLZ). The search for and development of natural compounds for the prevention of obesity when taking antipsychotic drugs is an urgent task. The biopolymer chitosan (Chi) and its derivatives have lipid-lowering and anti-diabetic properties, which makes them potential therapeutic substances for use in the treatment of metabolic disorders. The purpose of this work was to analyze the effect of the natural biopolymer Chi, its derivative N-succinyl chitosan (SuChi), and Orlistat (ORL) as a control on the effects caused by the intake of OLZ in a mouse model. Methods: Mice were fed with pearl barley porridge mixed with OLZ or combinations OLZ + Chi, OLZ + SuChi, or OLZ + ORL for 2 months. The weight, lipid profile, blood chemokines, expression of genes associated with appetite regulation, and behavior of the mice were analyzed in dynamics. Results: For the first time, data were obtained on the effects of Chi and SuChi on metabolic changes during the co-administration of antipsychotics. Oral OLZ increased body weight, food and water intake, and glucose, triglyceride, and cholesterol levels in blood. ORL and SuChi better normalized lipid metabolism than Chi, decreasing triglyceride and cholesterol levels. OLZ decreased the production of all chemokines tested at the 4th week of treatment and increased CXCL1, CXCL13, and CCL22 chemokine levels at the 7th week. All of the supplements corrected the level of CXCL1, CXCL13, and CCL22 chemokines but did not recover suppressed chemokines. SuChi and ORL stimulated the expression of satiety associated proopiomelanocortin (POMC) and suppressed the appetite-stimulating Agouti-related protein (AgRP) genes. All supplements improved the locomotion of mice. Conclusions: Taken collectively, we found that SuChi more than Chi possessed an activity close to that of ORL, preventing metabolic disorders in mice fed with OLZ. As OLZ carries positive charge and SuChi is negatively charged, we hypothesized that SuChi's protective effect can be explained by electrostatic interaction between OLZ byproducts and SuChi in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Obesity and hypertension have become an international health issue, with detrimental consequences on patients. Obesity and hypertension share common pathophysiological mechanisms, such as overactivity of the renin–angiotensin–aldosterone and the sympathetic nervous systems, insulin resistance, and disruption of the leptin pathway. Approved therapies for obesity and overweight include phentermine/topiramate, orlistat, naltrexone/bupropion, the glucagon-like peptide-1 receptor agonists liraglutide and semaglutide, tirzepatide, and bariatric surgery. This review gives the clinical data in a thorough manner and explains in detail how each of the previously mentioned therapies affects blood pressure levels. [ABSTRACT FROM AUTHOR]

The rising prevalence of obesity has become a significant concern in both high income and low income countries. Addressing obesity has challenges due to the limitations in current treatment options. Dietary modifications have become a common approach in managing obesity and its associated risks. The study was aimed atinvestigating the anti-obesity effects of the methanol extract of Shorea tumbuggaia, focusing specifically on its ability to inhibit pancreatic lipase activity. Shorea tumbuggaia stem bark methanolic preparation was screened for total phenolic content and subjected to phytochemical tests for presence of secondary metabolites. The pancreas of a chicken was used to extract the lipase enzyme. Lipase inhibitory activity of various methanol extract concentrations was assessed using olive oil as the substrate. Additional docking investigations of Shorea tumbuggaia components were made to investigate the role in regulating obesity and its associated issues. The study revealed that the extract has exhibited concentration dependent inhibition of pancreatic lipase activity. The study findings on Shorea tumbuggaia lipase inhibitory activity are encouraging which may be due to the existence of secondary metabolites causing the inhibitory action. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Obesity is a non‐communicable complex disease that is the fifth leading cause of death worldwide. According to a novel viewpoint, the brain plays a significant role in the central regulation of satiety and energy homeostasis. Because of its rich nutritional profile and versatile uses, oat (Avena sativa) is one of the most popular functional foods recommended by many nutritionists. The anti‐obesity effect of oat was hypothesized, focusing on the brain as the target organ. In the current study, the interplay between brain biomarkers, obesity, and its related complications was evaluated in diet‐induced obese rats for 25 weeks, in which 60 adult male white albino Wistar rats were divided into three control and seven treatment groups given oat extracts in a dose‐dependent manner.Oat significantly improved obesity‐related metabolic complications. In terms of brain function, oat significantly increased dopaminergic signaling, brain‐derived neurotrophic factor levels, vaspin, irisin, and uncoupling protein‐1 brain levels, while decreasing the expression of agouti‐related peptide and neuropeptide Y (P‐value < 0.05).The current study proposes oat supplementation as a new conceptual framework with numerous implications for hedonic and homeostatic mechanisms that control satiety. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Numerous digestive system adverse events (dsAEs) have been observed during the use of anti-obesity medications (AOMs), leading to concerns about the safety of these medications. However, most current studies are limited to the association of one class of drugs with specific digestive disorders, and there is no cascading analysis of AOMs in the digestive system. This study aims to use data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) for a stratified analysis of the reported associations between AOMs and dsAEs. Methods: We analyzed adverse event reports submitted to FAERS between January 2015 and December 2023 related to obesity treatment. It is important to note that FAERS data cannot establish causality or incidence rates. Pharmacovigilance (PV) signals were detected by disproportionate analyses through proportionate reporting ratio (PRR), reporting odds ratios (ROR), and information components (IC) to detect dsAEs associated with AOMs. Reporting rates, severity, and response outcomes of digestive adverse events were compared across AOMs by multivariate logistic regression analysis. Results: Among 34,396 adverse events (AEs) related to obesity treatment, 8844 dsAEs were analyzed. Comparing with semaglutide and liraglutide, tirzepatide exhibited fewer reported dsAEs while semaglutide and liraglutide showed a high correlation with non-lethal pancreatitis reports. Bupropion-naltrexone (31.65%) reported the highest number of dsAEs, and a PV signal was detected in mouth and lips AEs (ROR = 2.97, 95% CI: 2.42–3.6). Orlistat (ROR = 3.30, 95% CI: 3.08–3.55) exhibited the highest association with gastrointestinal AEs compared to other AOMs. PV signal for hepatobiliary AEs (ROR = 6.13, 95% CI: 3.45–10.88) with phentermine-topiramate still needs further clarification. Conclusions: Tirzepatide may be considered for patients with a history of digestive system disease or an elevated risk of pancreatitis based on the pattern of reported dsAEs. Caution is needed for the orofacial AEs when using bupropion-naltrexone. Orlistat has a higher reporting rate of gastrointestinal AEs, but these events are typically less severe. Phentermine-topiramate's association with liver impairment requires further clinical investigation. This article provides insights into the reported associations between AOMs and dsAEs, which may aid clinicians in making more informed decisions about individualizing medication and managing potential adverse events. [ABSTRACT FROM AUTHOR]

Aims: Approximately 30–49% of heart failure (HF) patients are living with obesity. The recommended body mass index (BMI) for the general population is 18.5–24.9 kg/m2. The obesity paradox suggests that HF patients with obesity (HFpwO) have a better prognosis compared to normal BMI. Guideline recommendations on ideal BMI for HFpwO are limited. This systematic review aims to examine the evidence base for intentional weight loss in HFpwO on the following parameters: mortality, hospitalization, symptoms, quality of life (QOL), effects on left ventricular ejection fraction (LVEF) and adverse events. Methods and results: A total of 22 studies were identified: lifestyle intervention (n = 9), pharmacotherapy (n = 3), bariatric surgery (n = 10). Mortality and hospitalization, symptoms, QOL, and LVEF were reported in 8, 15 and 14 studies, respectively. All studies had moderate to high risk of bias except one randomized controlled trial (RCT) which evaluated semaglutide in HF with preserved ejection fraction (HFpEF) patients. Semaglutide resulted in weight loss with improvement in QOL. Lifestyle intervention led to weight loss, minimal adverse events, and improvement in symptoms in both HF with reduced ejection fraction (HFrEF) and HFpEF patients. In six observational studies, bariatric surgery in HFrEF patients achieved weight loss and improvement in LVEF safely in most patients but some patients developed worsening HF perioperatively. Conclusion: There is a need for high‐quality adequately powered RCTs on intentional weight loss in HFpwO with survival and hospitalization outcomes. All forms of weight loss intervention studied in this review were likely to result in significant weight loss, improved symptoms and QOL. Careful monitoring is required due to an increase in certain adverse events. [Correction added on 11 September 2024, after first online publication: The sub‐headings 'Aims', 'Methods and results' and 'Conclusion' have been added in this version.] [ABSTRACT FROM AUTHOR]

Pistacia species (P. spp) have been used as a treatment for various diseases, including diabetes and inflammation. This study aimed to identify the main components of flavonoids in Pistacia species and evaluate the effect of aqueous extracts of P. spp on pancreatic enzymes and on cancer cells associated with obesity in colon and rectum. HPLC was used to identify the major components of flavonoids. The potent inhibitory effect of Pistacia species against pancreatic α-amylase, α-glucosidase and lipase was examined. The antiproliferative efficacy of the plant extract against several colorectal cancer cell lines were then measured. The main flavonoids component found in Pistacia species are quercetin-3-β-D-glucoside, rutin, kaempferol and vitexin. The starch blockade IC50 (µg/mL) of Pistacia species in a descending order were: P. lentiscus leaves: 1.09±0.01; P. atlantica leaves: 0.96±0.09 and P. atlantica fruits: 0.48±0.02. Pistacia species exerted promising inhibition effect for pancreatic lipase (PL). Besides the aglycones of P. atlantica leaves, all the tested aqueous extracts exerted appreciably novel antiproliferative activity against the tested colorectal cancer cell lines. This study provides useful indication for the Pistacia species as a potential novel therapeutic agent against diabesity and cancer. [ABSTRACT FROM AUTHOR]

An analysis of a global database documenting adverse drug reactions has detected a disproportional occurrence of suicidal ideation associated with use of the glucagon‐like peptide‐1 (GLP‐1) receptor agonist semaglutide. This association was not present with use of the GLP‐1 receptor agonist liraglutide or with other medications used to treat type 2 diabetes or obesity. Study results were published online Aug. 20, 2024 in JAMA Network Open. [ABSTRACT FROM AUTHOR]

Abstract Background Weight gain and metabolic disorders are commonly induced by antipsychotics. Orlistat is a lipase inhibitor used for weight control. The effect of orlistat on weight gain and metabolic disturbances in people (especially women) treated with antipsychotics has not been sufficiently studied. This study aimed to investigate the efficacy of orlistat in mitigating antipsychotic-induced weight gain and abnormal glycolipid metabolism. Methods Patients with schizophrenia or bipolar disorder with a weight gain ≥ 7% after taking antipsychotics were recruited. Participants were randomly allocated to two groups: one received eight weeks of orlistat (360 mg/day) and the other received a placebo. Anthropometric and fasting serum biochemical parameters were measured at baseline, week 4 and week 8. Results Sixty individuals (orlistat:placebo = 32:28) participated in the study. After controlling for the study center, the eight-week changes in body mass index (BMI), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-CH) and low-density lipoprotein cholesterol (LDL-CH) were significantly different between the groups. According to the mixed linear models, CHOL and LDL-CH were significantly lower in the orlistat group than in the control group at week 8. The week 0-to-8 slopes of BMI, CHOL and LDL-CH were also significantly lower in the orlistat group. Conclusions These findings suggested that orlistat is an effective intervention for attenuating weight gain and serum lipid disturbances in antipsychotic-treated patients. Trial registration ClinicalTrials.gov NCT03451734.

Background: Orlistat (ORS) and metformin (MEF) are robustly used as well-established clinical drugs for the treatment for both obesity and the consequences of diabetes mellitus. Additionally, no study has been conducted to explore the consequence of the combination of both ORS and MEF on the kidneys of rats with obesity-induced renal injury (OBS). Objectives: Therefore, the objective of the current research was designed to explore the possible ameliorative effects of either ORS and/or MEF or their combination against obesity (OBS) induced experimental renal oxidative stress. Methods: Renal oxidative stress was investigated at redox histopathological and immunohistological points in the kidney tissues. Results: The levels of urea, uric acid, and creatinine increased with the obesity effect; in addition, the myeloperoxidase (MPO) and xanthine oxidase (XO) activators were elevated significantly with the induction of OBS. The levels of non-enzymatic antioxidants (glutathione and thiol) declined sharply in OBS rats as compared to the normal group. Conclusion: The data displayed that the combination of both ORS and MEF declined the obesity effects significantly by reducing the level of peroxidation (MDA), and enhancement intracellular antioxidant enzymes. These biochemical findings were supported by histopathology, immunohistochemistry, and Masson-Trichrome evaluation, which showed minor morphological changes in the kidneys of rats. [ABSTRACT FROM AUTHOR]

Dose-scale pharmacodynamic bioequivalence is recommended for evaluating the consistency of generic and innovator formulations of certain locally acting drugs, such as orlistat. This study aimed to investigate the standard methodology for sample size determination and the impact of study design on dose-scale pharmacodynamic bioequivalence using orlistat as the model drug. A population pharmacodynamic model of orlistat was developed using NONMEM 7.5.1 and utilized for subsequent simulations. Three different study designs were evaluated across various predefined relative bioavailability ratios of test/reference (T/R) formulations. These designs included Study Design 1 (2×1 crossover with T1 60 mg, R1 60 mg, and R2 120 mg), Study Design 2 (2×1 crossover with T2 120 mg, R1 60 mg, and R2 120 mg), and Study Design 3 (2×2 crossover with T1 60 mg, T2 120 mg, R1 60 mg, and R2 120 mg). Sample sizes were determined using a stochastic simulation and estimation approach. Under the same T/R ratio and power, Study Design 3 required the minimum sample size for bioequivalence, followed by Study Design 1, while Study Design 2 performed the worst. For Study Designs 1 and 3, a larger sample size was needed on the T/R ratio < 1.0 side for the same power compared to that on the T/R ratio > 1.0 side. The opposite asymmetry was observed for Study Design 2. We demonstrated that Study Design 3 is most effective for reducing the sample size for orlistat bioequivalence studies, and the impact of T/R ratio on sample size shows asymmetry. [ABSTRACT FROM AUTHOR]

Background: Weight gain and metabolic disorders are commonly induced by antipsychotics. Orlistat is a lipase inhibitor used for weight control. The effect of orlistat on weight gain and metabolic disturbances in people (especially women) treated with antipsychotics has not been sufficiently studied. This study aimed to investigate the efficacy of orlistat in mitigating antipsychotic-induced weight gain and abnormal glycolipid metabolism. Methods: Patients with schizophrenia or bipolar disorder with a weight gain ≥ 7% after taking antipsychotics were recruited. Participants were randomly allocated to two groups: one received eight weeks of orlistat (360 mg/day) and the other received a placebo. Anthropometric and fasting serum biochemical parameters were measured at baseline, week 4 and week 8. Results: Sixty individuals (orlistat:placebo = 32:28) participated in the study. After controlling for the study center, the eight-week changes in body mass index (BMI), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-CH) and low-density lipoprotein cholesterol (LDL-CH) were significantly different between the groups. According to the mixed linear models, CHOL and LDL-CH were significantly lower in the orlistat group than in the control group at week 8. The week 0-to-8 slopes of BMI, CHOL and LDL-CH were also significantly lower in the orlistat group. Conclusions: These findings suggested that orlistat is an effective intervention for attenuating weight gain and serum lipid disturbances in antipsychotic-treated patients. Trial registration: ClinicalTrials.gov NCT03451734. [ABSTRACT FROM AUTHOR]

Objective: Nonalcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant contributor to chronic liver disease worldwide. Orlistat blocks intestinal fat absorption, leading to decreased liver fat content. Therefore, it is a viable option for NAFLD management. Methods: We performed a systematic review and metaanalysis using randomized controlled trials (RCTs). We used mean difference (MD) to pool continuous outcomes presented with the corresponding confidence interval (CI). Results: We included four RCTs with a total of 379 patients. Orlistat was effective in reducing liver fat content (MD: −5.02, 95% CI [–7.23, −2.82], P = 0.00001), alanine transferase (MD: −10.03, 95% CI [–17.80, −2.26], P = 0.01), aspartate transferase (MD: −4.29, 95% CI [–7.59, −0.99], P = 0.01), waist circumference (MD: −3.18, 95% CI [–4.25, −2.10], P = 0.00001), body mass index (MD: −1.03, 95% CI [–1.34, −0.73], P = 0.00001), total cholesterol (MD: −3.75, 95% CI [–4.02, −3.49], P = 0.00001), and low-density lipoprotein (MD: −3.83, 95% CI [–4.05, −3.61], P = 0.00001). However, orlistat was associated with increased serum triglycerides (MD: 7.46, 95% CI [6.48, 8.44], P = 0. 00001). Conclusion: Orlistat is a viable option for NAFLD management; however, it increases triglyceride levels. Larger RCTs are required. [ABSTRACT FROM AUTHOR]

Background: There is an increase in the prevalence of obesity-related reproductive disorders, particularly anovulation and infertility so, this indicates use of insulin sensitizing agents such as metformin and use of weight reduction agents such as orlistat in order to achieve reduction of BMI, reduce androgenic effect and improve ovulation. To the best of our knowledge, no studies in this respect was performed in Zagazig University before. Our study aimed to asses the effect of orlistat versus metformin on improvement of ovulation rate, weight loss and lipid and hormonal profile. Methods: This randomized controlled trial was conducted at Zagazig University Hospital's outpatient clinic on 132 patients diagnosed with polycystic ovary syndrome. All cases were subjected to full history taking including, general examination and laboratory investigations including FSH, LH, TSH, free T4, free testosterone and prolactin level. Results: There was no statistical significant difference between both groups as regard ovulation rate. There was significant changes between studied groups at 1st and 3rd month as regard anthropometric data except BMI was insignificant at 1st month. Also, there was significant difference between studied groups as regard to laboratory data at 1st and 3rd month except FSH at 3rd month was insignificant. Conclusions: We advise choosing metformin as a safe and effective treatment over orlistat for the treatment of polycystic ovarian syndrome, preferably in conjunction with weight loss and a healthy lifestyle. [ABSTRACT FROM AUTHOR]

Policy PointsHealth policymakers have insufficiently addressed care for people with obesity (body mass index ≥ 30 kg/m2) in the United States. Current federal policies targeting obesity medications reflect this unfortunate reality.We argue for a novel policy framework to increase access to effective obesity therapeutics and care, recognizing that, though prevention is critical, the epidemic proportions of obesity in the United States warrant immediate interventions to augment care.Reducing barriers to and improving the quality of existing anti‐obesity medications, intensive behavioral therapy, weight management nutrition and dietary counseling, and bariatric surgery are critical. Moreover, to ensure continuity of care and patient–clinician trust, combating physician and broader weight stigma must represent a central component of any viable obesity care agenda. [ABSTRACT FROM AUTHOR]

Background: Orlistat (Orli) is an anti-obesity medication that has been approved by the US Food and Drug Administration. It has relatively limited oral bioavailability with promising inhibitory effects on cell proliferation as well as reducing the growth of tumors. Aims: This investigation was done to evaluate the potential protective effect of Tamoxifen/Orlistat nanocrystals alone or in combination against Solid Ehrlich Carcinoma (SEC) and to clarify the possible underlying influences. Materials and methods: The liquid antisolvent precipitation technique (bottom-up technology) was utilized to manufacture Orlistat Nanocrystals. To explore potential causes for the anti-tumor action, female Swiss Albino mice bearing SEC were randomly assigned into five equal groups (n = 6). Group 1: Tumor control group, group 2: Tam group: tamoxifen (0.01 g/kg, IP), group 3: Free-Orli group: orlistat (0.24 g/kg, IP), group 4: Nano-Orli: orlistat nanocrystals (0.24 g/kg, IP), group 5: Tam–Nano-Orli: Both doses of Tam and Nano-Orli. All treatments were administered for 16 days. Key findings: The untreated mice showed development in the tumor volume and weight. As well as histopathology results from these mice revealed many tumor large cells as well as solid sheets of malignant cells. Also, untreated mice showed raised VEGF and TGF-1beta content. Moreover, results of gene expression in the SEC-bearing mice noted upregulation in HIF-1α, MMP-9, Bcl-2, and P27 gene expression and downregulation of TXNIP, BAX, and P53 gene expression. On the other hand, administrated TAM, Free-Orli, Nano-Orli, and a combination of Tam-Nano-Orli distinctly suppressed the tumor effects on estimated parameters with special reference to Tam-Nano-Orli. Significance: The developed Tamoxifen/Orlistat nanocrystals combination could be considered a promising approach to augment antitumor effects.

Abstract 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

Context: Atorvastatin is typically used in the treatment of dyslipidemia. However, the interest in using anti-obesity medications such as orlistat has grown rapidly as obesity is one of the variables associated with dyslipidemia. Aims: To synthesize the findings from previous studies published to date on the potential effects of atorvastatin and tetrahydrolipstatin (orlistat) on the levels of serum LDL. Methods: A systematic review and meta-analysis of research reports and RCTs about atorvastatin and orlistat on LDL levels from articles published in Medline, PubMed, and Scopus from 2012 to 2022 were conducted using PRISMA and RevMan 5.4 software. Results: From 9 final included articles, 6 focused on atorvastatin and 3 on orlistat. Five papers on atorvastatin reported a significant decrease in LDL level, whereas only 2 from orlistat papers. There is a significant decrease in LDL level associated with Atorvastatin treatment (p = 0.04, CI = 1.58, 56.81, I2 = 99%), but not with orlistat (p = 0.05, CI = 0.10, 17.69, I2 = 93%). Conclusions: Here, it is shown that atorvastatin instead of orlistat has a significant effect on decreasing LDL serum levels in dyslipidemia patients.

Summary: This systematic review and meta‐analysis evaluated the efficacy of anti‐obesity agents for hormonal, reproductive, metabolic, and psychological outcomes in polycystic ovary syndrome (PCOS) to inform the 2023 update of the International Evidence‐based Guideline on PCOS. We searched Medline, EMBASE, PsycInfo, and CINAHL until July 2022 with a 10‐year limit to focus on newer agents. Eleven trials (545 and 451 participants in intervention and control arms respectively, 12 comparisons) were included. On descriptive analyses, most agents improved anthropometric outcomes; liraglutide, semaglutide and orlistat appeared superior to placebo for anthropometric outcomes. Meta‐analyses were possible for two comparisons (exenatide vs. metformin and orlistat + combined oral contraceptive pill [COCP] vs. COCP alone). On meta‐analysis, no differences were identified between exenatide versus metformin for anthropometric, biochemical hyperandrogenism, and metabolic outcomes, other than lower fasting blood glucose more with metformin than exenatide (MD: 0.10 mmol/L, CI 0.02–0.17, I2 = 18%, 2 trials). Orlistat + COCP did not improve metabolic outcomes compared with COCP alone (fasting insulin MD: −8.65 pmol/L, −33.55 to 16.26, I2 = 67%, 2 trials). Published data examining the effects of anti‐obesity agents in women with PCOS are very limited. The role of these agents in PCOS should be a high priority for future research. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastomas are the most aggressive brain tumors, and affected patients still only have an extremely poor prognosis with today's therapeutic options. Further developments are still necessary, particularly in therapeutic approaches. Orlistat can act as an antitumor agent as it inhibits fatty acid synthase, decreases tumor cell proliferation, and stimulates tumor cell apoptosis. Investigations conducted on breast, pancreatic, hepatic, and colorectal tumors showed that FASN—fatty acid synthase, a protein that catalyzes the de novo synthesis of long-chain fatty acids—is strongly upregulated. Using an animal model, we tested whether the drug's effects could be demonstrated visually, quantitatively, and by texture analysis based on MR studies. Histology and immunochemistry were used as references. The key results of the present study are as follows: Firstly, a significant difference was found between orlistat-treated and untreated tumors in MRI studies based on morphology and texture analyses. Secondly, the expression of FASN was reduced in the orlistat group, which, however, did not result in a higher apoptosis rate in the treatment group. Our findings suggest that some effects of orlistat on tumor cell proliferation must have taken place during therapy. Further studies should investigate the effects of FASN inhibition when combined with targeted therapies. Background: This study aimed to investigate the effects of tetrahydrolipstatin (orlistat) on heterotopic glioblastoma in mice by applying MRI and correlating the results with histopathology and immunochemistry. Methods: Human glioblastoma cells were injected subcutaneously into the groins of immunodeficient mice. After tumor growth of >150 mm3, the animals were assigned into a treatment group (n = 6), which received daily intraperitoneal injections of orlistat, and a control group (n = 7). MRI was performed at the time of randomization and before euthanizing the animals. Tumor volumes were calculated, and signal intensities were analyzed. The internal tumor structure was evaluated visually and with texture analysis. Western blotting and protein expression analysis were performed. Results: At histology, all tumors showed high mitotic and proliferative activity (Ki67 ≥ 10%). Reduced fatty acid synthetase expression was measured in the orlistat group (p < 0.05). Based on the results of morphologic MRI-based analysis, tumor growth remained concentric in the control group and changed to eccentric in the treatment group (p < 0.05). The largest area under the receiver operating curve of the predictors derived from the texture analysis of T2w images was for wavelet transform parameters WavEnHL_s3 and WavEnLH_s4 at 0.96 and 1.00, respectively. Conclusions: Orlistat showed effects on heterotopically implanted glioblastoma multiforme in MRI studies of mice based on morphologic and texture analysis. [ABSTRACT FROM AUTHOR]

The objective of the present study was to evaluate the antiobesity potential of various plant (leaves or seed) extracts through a modified in vitro lipase inhibitory activity assay. Dimethyl sulphoxide (DMSO, negative control or solvent) extracts as cold infusion of leaves and seeds of some plants were studied for lipase inhibitory potential using porcine pancreatic lipase enzyme, p-nitro phenyl acetate and orlistat (as positive control or standard inhibitor). Among the leaves, the Urtica dioica showed the best pancreatic lipase inhibition activity (52.0 %). On the other hand, among the seeds, Trachyspermum ammi showed the highest per cent lipase inhibition (91.68 %). Among six leaves' and seven seeds' extract, it was evident that the seeds showed better pancreatic lipase inhibition activity over the leaves in the study. The lipase inhibition was found to be in the range of 34.43 to 91.68 % for the plants in study. DMSO extract of the plants under the study showed significant pancreatic lipase inhibitory activity indicating strong antiobesity activity. Therefore, the plants can be further investigated for the identification and isolation of chief bioactive constituents for developing the lead molecules for obesity treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is a persistent chronic condition. It is associated with an increased risk of premature death and the development of accompanying diseases. According to statistical data, half of the population struggles with excessive body weight, with one in five Poles being obese. [2] Aim: Our study aimed to evaluate the current literature on pharmacotherapy for obesity available in Poland using the PubMed database. We emphasize the crucial importance of an individualized patient approach to attain therapeutic success, aligning with the latest guidelines and scientific research. A brief description of the state of knowledge: In Poland, we have three registered medications intended for the treatment of obesity: naltrexone/bupropion, liraglutide, and orlistat. It's crucial that they assist in weight reduction, hence they should be used alongside a proper diet and physical activity, not as the sole form of treatment. Using them assists in achieving therapeutic targets determined in partnership with the patient, and lowers levels of particular indicators linked to chronic inflammation and arterial issues. Moreover, they diminish the chances of complications and early mortality due to the advancement of the condition. Summary: Obesity is a serious condition, and there should be no fear in incorporating pharmacotherapy in patients with it. It is incredibly important to effectively treat this disease and take proactive health measures, even at the stage of overweight, considering it as a precursor to obesity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD), which can manifest as nonalcoholic steatohepatitis (NASH) or severe fibrosis, is the most prevalent chronic liver disease in children and adolescents. However, there is no proven cure for it so far. This study was conducted to determine whether adolescents with NAFLD would improve with treatment intervention with orlistat. This study is a randomized controlled trial (RCT). Fifty-three adolescents with overweight/obese as well as with NAFLD randomly allocated to receive orlistat (n = 27) or placebo as control (n = 26) for 12 weeks. In addition, NAFLD activity score, anthropometric factors, biochemical parameters including serum levels of lipid profiles, liver enzyme, and glucose metabolism taken from subjects at baseline and end of the study were investigated. The findings of our article indicated that orlistat improves liver enzymes (alanine transaminase and aspartate transaminase) (P = < 0.001), steatosis score (P = 0.001), NAFLD activity score (P = < 0.001), weight (P = < 0.001), body mass index (BMI) (P = < 0.001), waist circumferences (WC) (P = < 0.001), BMI-Z score (P = < 0.001), glucose metabolism (P = 0.001), total cholesterol (TC) (P = 0.009), low density lipoprotein-cholesterol (LDL) (P = < 0.001), and high density lipoprotein-cholesterol HDL levels (P = 0.014) compared to the control group after adjusting for possible confounders for 12 weeks. However, no significant changes were observed on triglyceride (TG) following intake of orlistat compared to placebo after adjusting for confounders. Conclusion: The findings of our study reported that orlistat improved NAFLD-related factors and metabolic syndrome-related factors compared to placebo for 12 weeks. Trial Registration: (Clinical trial registry number: IRCT20220409054467N2, with a registration date of 2022–05-13). What is Known: • Among the interventions of interest for the management of pediatric NAFLD, we can mention lifestyle and pharmaceutical measures. What is New: • This study was conducted to determine whether adolescents with NAFLD would improve with treatment intervention with orlistat. • The findings of our study reported that orlistat improved NAFLD-related factors and metabolic syndrome-related factors compared to placebo for 12 weeks. [ABSTRACT FROM AUTHOR]

Objective: Based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, we analyzed the signals of potential adverse events (AEs) of orlistat in the real world to provide a reference for its safe clinical use. Methods: The FAERS database and OpenVigil 2.1 were used to obtain data on adverse events of orlistat from the first quarter of 2004 to the first quarter of 2023, and to analyze the population in which the adverse events occurred. And the signals of their potential adverse events were mined using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and empirical Bayesian geometric mean (EBGM). Result: A total of 21,079 reports of adverse events with orlistat as the primary suspected drug were collected in this study. Using four disproportionate analyses, we screened 117 preferred terms (PTs) involving 18 system organ classes (SOCs). We found that the most common adverse events at SOC level for orlistat remained ''gastrointestinal disorders'', while ''metabolism and nutrition disorders'', ''renal and urinary disorders'', ''musculoskeletal and connective tissue disorders'' and ''hepatobiliary disorders'' also ranked high in the number of case reports. In addition, at the PT level, we identified several new signals of adverse events not mentioned in the specification, including ''lipiduria'', ''anal haemorrhage'', ''rectal haemorrhage'', ''haematochezia'', ''sigmoiditis'', ''diverticulitis'' and ''muscle spasms''. Conclusion: Most of the adverse events found in this study are consistent with the results described in the drug label. At the same time, we also found some new adverse events, which require more prospective studies to verify and elucidate their relationship with orlistat.

Abstract Obesity is a chronic, recurring, progressive disease and a major public health problem associated with several other diseases that lead to disability, morbidity, and mortality. The prevalence of obesity has increased at pandemic levels, along with increasing weight-related comorbidities and deaths worldwide. Lifestyle interventions alone provide clinically significant long-term weight loss in only a small proportion of individuals, and bariatric surgery is not suitable or desirable for all patients. Historically, anti-obesity medications achieved a mean efficacy with weight loss between 5 and 10%, which significantly impacted several comorbidities and risk factors, but the average efficacy of these medications remained lower than that expected by both patients and health care professionals and eventually curbed long-term use. Moreover, there is no direct evidence on the impact of anti-obesity medications on cardiovascular outcomes. Semaglutide is a newer anti-obesity medication that changes the overall landscape, as phase 3 studies show a mean weight loss near the 15% threshold and significant proportions of patients with a weight loss of greater than 20%. In this review, we focus on the currently available anti-obesity medications, discuss the results of semaglutide, and present perspectives on the future of obesity treatment after semaglutide.

Introduction: Obesity is known to lead to the development of metabolic disorders and Erythrina subumbrans (Hassk.) Merr has shown the potential in alleviating some diseases. This study aimed to assess the anti-obesity activity of the ethanol extract of E. subumbrans leaves (EES) in obese Wistar albino rats. Methods: The rats were randomly assigned to eight groups (n = 5): normal group (no obesity inducement, treated with standard feed); high fructose (60%)-induced obesity (obesity induced, no treatment); control-1 group (obesity-induced, treated with orlistat 10.8 mg/kg BW); control-2 group (obesity-induced, treated with Isprinol 45 mg/kg); control-3 group (obesity-induced, treated with metformin 45 mg/kg); three test groups (obesity-induced, treated with EES 100, 200, and 400 mg/kg, respectively). The obesity inducement was conducted for 7 weeks. The rats were observed for body weight (BW), feed residue, feces index, triglycerides, organ index, and leucocyte profile. Results: The screening for secondary metabolites in EES revealed the presence of flavonoids, alkaloids, saponins, polyphenols, and tannins. EES decreased the percentage of BW gain, appetite, organ index (spleen), total fat, triglycerides, and leucocyte profile of the rats. Conclusion: The ethanol extract of the leaves of E. subumbrans has the potential to be developed as an anti-obesity agent, although the molecular mechanism of its pathway modulation is still unknown.

The aim of the present study was to make a polyherbal formulation of three herbs that would offset the negative effects of the high-fat cafeteria diet on rats and the beneficial effects of exercise. The ingredients for this herbal remedy included a water extract of Garcinia cambogia fruit, Trigonella foenum-graecum seed, and Glycyrrhiza glabra root in a 1:1:1 ratio. Nine groups of six male Wistar albino rats were chosen. Animals in Group I were normal and fed a standard diet; animals in Group II were given HFCD to prevent disease; animals in Group III were given HFCD plus exercise; while animals in Groups IV and V were given PHF at doses of 400 and 200 mg/kg p. o. Daily, respectively, in addition to HFCD; while animals in Groups VI and VII were exercised obese rats prevented from gaining more weight had their serum glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels lowered. HDL cholesterol was raised. Further, the liver biopsy showed increased mononuclear cells; fat globules numbered less; and the enzymes and cells that are regenerating were at lower levels. The polyherbal formulation plus exercise exhibited significant anti-obesity efficacy at 400 mg/kg p. o.; the effect was equivalent to orlistat plus exercise. The research employed HFCD-induced obese rats as a model to investigate the joint effects of PHF and exercise against obesity.

Obesity and hypertension have become an international health issue, with detrimental consequences on patients. Obesity and hypertension share common pathophysiological mechanisms, such as overactivity of the renin–angiotensin–aldosterone and the sympathetic nervous systems, insulin resistance, and disruption of the leptin pathway. Approved therapies for obesity and overweight include phentermine/topiramate, orlistat, naltrexone/bupropion, the glucagon-like peptide-1 receptor agonists liraglutide and semaglutide, tirzepatide, and bariatric surgery. This review gives the clinical data in a thorough manner and explains in detail how each of the previously mentioned therapies affects blood pressure levels.

Background: The issue of human mental health is gaining more and more attention nowadays. However, most mental disorders are treated with antipsychotic drugs that cause weight gain and metabolic disorders, which include olanzapine (OLZ). The search for and development of natural compounds for the prevention of obesity when taking antipsychotic drugs is an urgent task. The biopolymer chitosan (Chi) and its derivatives have lipid-lowering and anti-diabetic properties, which makes them potential therapeutic substances for use in the treatment of metabolic disorders. The purpose of this work was to analyze the effect of the natural biopolymer Chi, its derivative N-succinyl chitosan (SuChi), and Orlistat (ORL) as a control on the effects caused by the intake of OLZ in a mouse model. Methods: Mice were fed with pearl barley porridge mixed with OLZ or combinations OLZ + Chi, OLZ + SuChi, or OLZ + ORL for 2 months. The weight, lipid profile, blood chemokines, expression of genes associated with appetite regulation, and behavior of the mice were analyzed in dynamics. Results: For the first time, data were obtained on the effects of Chi and SuChi on metabolic changes during the co-administration of antipsychotics. Oral OLZ increased body weight, food and water intake, and glucose, triglyceride, and cholesterol levels in blood. ORL and SuChi better normalized lipid metabolism than Chi, decreasing triglyceride and cholesterol levels. OLZ decreased the production of all chemokines tested at the 4th week of treatment and increased CXCL1, CXCL13, and CCL22 chemokine levels at the 7th week. All of the supplements corrected the level of CXCL1, CXCL13, and CCL22 chemokines but did not recover suppressed chemokines. SuChi and ORL stimulated the expression of satiety associated proopiomelanocortin (POMC) and suppressed the appetite-stimulating Agouti-related protein (AgRP) genes. All supplements improved the locomotion of mice. Conclusions: Taken collectively, we found that SuChi more than Chi possessed an activity close to that of ORL, preventing metabolic disorders in mice fed with OLZ. As OLZ carries positive charge and SuChi is negatively charged, we hypothesized that SuChi’s protective effect can be explained by electrostatic interaction between OLZ byproducts and SuChi in the gastrointestinal tract.

The oral consumption of alcohol (ethanol) has a long tradition in humans and is an integral part of many cultures. The causal relationship between ethanol consumption and numerous diseases is well known. In addition to the well-described harmful effects on the liver and pancreas, there is also evidence that ethanol abuse triggers pathological skin conditions, including acne. In the present study, we addressed this issue by investigating the effect of ethanol on the energy metabolism in human SZ95 sebocytes, with particular focus on qualitative and quantitative lipogenesis. It was found that ethanol is a strong trigger for lipogenesis, with moderate effects on cell proliferation and toxicity. We identified the non-oxidative metabolism of ethanol, which produced fatty acid ethyl esters (FAEEs), as relevant for the lipogenic effect—the oxidative metabolism of ethanol does not contribute to lipogenesis. Correspondingly, using the Seahorse extracellular flux analyzer, we found an inhibition of the mitochondrial oxygen consumption rate as a measure of mitochondrial ATP production by ethanol. The ATP production rate from glycolysis was not affected. These data corroborate that ethanol-induced lipogenesis is independent from oxygen. In sum, our results give a causal explanation for the prevalence of acne in heavy drinkers, confirming that alcoholism should be considered as a systemic disease. Moreover, the identification of key factors driving ethanol-dependent lipogenesis may also be relevant in the treatment of acne vulgaris. [ABSTRACT FROM AUTHOR]

Colon cancer (COAD) is a prevalent gastrointestinal tumor, composed of a few cancer stem cells (CSCs). High expression of RNF183 drives colorectal cancer metastasis, but its role in COAD cell stemness is still unclear. Bioinformatics analyzed expression and enriched pathway of RNF183 in COAD tissue. IHC analyzed RNF183 protein expression in tumor tissue. CD133 + CD44+ CSCs were sorted by flow cytometry, and RNF183 expression in COAD cells or CSCs was detected by qPCR, western blot and immunofluorescence. CCK-8 assay assessed cell viability, and sphere formation assay tested cell sphere-forming ability. Western blot measured protein expression of stem cell markers. qPCR assayed expression of fatty acid oxidation genes. The ability of fatty acid oxidation was analyzed by detecting fatty acid metabolism. RNF183 was highly expressed in COAD and CD133 + CD44+ CSCs, and was enriched in fatty acid metabolism pathway. RNF183 expression was positively correlated with enzymes involved in fatty acid oxidation. RNF183 could promote COAD stemness and fatty acid oxidation. Rescue experiments showed that Orlistat (a fatty acid oxidation inhibitor) reversed stimulative impact of RNF183 overexpression on COAD stemness. RNF183 promoted COAD stemness by affecting fatty acid oxidation, which may be a new therapeutic target for inhibiting COAD development. [ABSTRACT FROM AUTHOR]

Background: Arq is a traditional Unani liquid formulation. In this study we explored Arq-Makoh, Arq-Badiyan and Arq-Kasni for their pharmacological potential to alleviate the symptoms of hyperlipidaemia and obesity and develop an amalgamation with modern drugs that have clinically well reported antihyperlipidaemic and antiobesity potential. Materials and methods: Rats were fed High Fat Diet for 4 weeks. 10 ml/kg of each of the three arqs were given alone and along with atorvastatin and orlistat daily for 28 days P.O. During the course of treatment body weight and food intake were carefully observed and after the end of the study, liver weight, heart weight, plasma lipid profile, blood glucose level, insulin and leptin level, serum lipase, lactate dehydrogenase, and antioxidant activity were studied in all treatment groups. Result: Both Arqs and Atorvastatin and Orlistat significantly reduced body weight, lipid profile in HFD fed rats. Arqs when given along with Atorvastatin and Orlistat produced more significant decrease in the serum lipid profile, serum lipase, atherogenic index, lactate Dehydrogenase and TBARS compared with HFD Control group and elevated the levels of HDL-C and SOD. Apart from antihyperlipidaemic and antiobesity effects the treatment groups showed a significant reduction in elevated fasting blood glucose levels (as a result of HFD model used in the study). The above parameters were further confirmed by histopathological studies. Conclusion: The present study indicates that Arq-Makoh, Arq-Badiyan and Arq-Kasni has lipid lowering potential and could potentiate the antihyperlipidaemic and antiobesity potential of Atorvastatin and Orlistat. [ABSTRACT FROM AUTHOR]

Fu tea is receiving increasing attention for its specific aroma, flavor, and dramatic functional benefits. Herein, we explored the effects and underlying mechanisms of Fu loose tea (FLT), Fu brick tea (FBT), and diet pills (orlistat) on a high-fat diet (HFD)-induced obesity. The results indicated that FLT and FBT administration effectively inhibited weight gain, glucose metabolic dysregulation, fat accumulation in organs, hepatic and kidney injury, and oxidative stress induced by HFD. Additionally, FLT and FBT treatments improved the lipid profiles and reduced the production of proinflammatory cytokines by regulating the expression levels of lipid metabolism- and inflammation-related genes. Furthermore, FLT and FBT ameliorated the gut microbiota dysbiosis in HFD-mice in a dose-dependent relationship by increasing the abundance of family Verrucomicrobiaceae and genus Akkermansia and Turicibacter and simultaneously reducing the abundance of family Erysipelotrichaceae and genus Bifidobacterium; in contrast, orlistat did not exert a regulatory effect on gut microbiota similar to FLT and FBT to improve HFD-induced obesity. KEGG analysis of gut microbiota annotation revealed that "metabolism" was the most enriched category. This study further provides a theoretical basis for FLT and FBT to be potential supplements to alleviate diet-induced obesity. [ABSTRACT FROM AUTHOR]

Introduction: Obesity can lead to death with associated high-risk diseases such as cardiovascular disease, diabetes, hypertension, stroke and cancer. Obesity results from an excessive dietary fat intake. Pancreatic lipase (PL) is an enzyme that plays a major role in hydrolyzing fats into monoacylglycerol and fatty acids that can be absorbed into the small intestine. One of the strategies to treat obesity is by reducing fat absorption via PL inhibition. This study aims to search for potential PL inhibitors from selected Malaysian plants capable of reducing fat absorption. Methods: Potential PL inhibitors were virtually screened using AutoDock Vina against reported phytochemical compounds from the peels, fruits and leaves of five selected citrus plants namely Citrus aurantifolia (C. aurantifolia), C. grandis, C. medica, C. hystrix and C. microcarpa. Results: The results were classified based on the free energy of binding into three groups: high, moderate, and low inhibition. Eight compounds exhibited high activity against PL. Citrus grandis contributed the highest number of compounds, followed by C. medica, C. microcarpa, C. aurantifolia, and C. hystrix. To validate these findings, 15 methanolic extracts from various parts of these citrus plants were subjected to in vitro bioassays. Notably, the fruit extract of C. medica demonstrated the most potent PL inhibition at 62.59%, possibly due to the presence of diosmetin-6-C-glucoside. Conclusions: In conclusion, virtual screening of small molecules derived from selected citrus plants offers valuable insights into molecular docking and C. medica emerges as a potential anti-obesity plant. [ABSTRACT FROM AUTHOR]