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Background and Objectives: Obesity and related disorders are an increasing global health problem. Achieving and maintaining long-term weight loss through lifestyle changes and/or pharmacological interventions have not met expectations. Dietary supplements and alternative treatments have also shown limited effectiveness in this regard. The consumption of green tea in general has been shown to benefit obese patients, with effects attributed to caffeine, catechins, polyphenols and other components. However, the potential of white tea to prevent and treat the negative effects of obesity has not been addressed so far. In this study, the effect of white tea (WT) consumption in obese individuals was anthropometrically and biochemically investigated. Materials and Methods: Based on anthropometric and biochemical assessments, the patients were assigned to the control, orlistat, metformin and WT groups. Patients were given a diet and exercise program and one of either orlistat, metformin or WT for 12 weeks. At the end of the 12th week, the anthropometric and biochemical measurements were reassessed. Results: Body weight, waist circumference and BMI parameters decreased significantly in all groups. TNF-α, IL-6, IL-1β and MMP-9 levels decreased significantly in the WT group. In addition, contrary to a significant elevation in HDL-C, the serum cholesterol, LDL-C and TG levels decreased significantly. Furthermore, leptin, ghrelin and asprosin levels decreased significantly. Serum glucose levels decreased significantly in all groups except for the control. In the WT group, while there was a significant decrease in the levels of serum PL MDA and 8-OHdG, the opposite was true for GSH. Conclusions: The oral consumption of WT, its availability and its potency in obesity treatment and prevention pave the way for further delineation of the mechanisms of actions of its bioactive compounds at the cellular and endocrinological levels.

Background Sorafenib resistance is a key impediment to successful treatment of patients with advanced hepatocellular carcinoma (HCC) and recent studies have reported reversal of drug resistance by targeting ferroptosis. The present study aimed to explore the association of fatty acid synthase (FASN) with sorafenib resistance via regulation of ferroptosis and provide a novel treatment strategy to overcome the sorafenib resistance of HCC patients. Methods Intracellular levels of lipid peroxides, glutathione, malondialdehyde, and Fe 2+ were measured as indicators of ferroptosis status. Biological information analyses, immunofluorescence assays, western blot assays, and co-immunoprecipitation analyses were conducted to elucidate the functions of FASN in HCC. Both in vitro and in vivo studies were conducted to examine the antitumor effects of the combination of orlistat and sorafenib and CalcuSyn software was used to calculate the combination index. Results Solute carrier family 7 member 11 (SLC7A11) was found to play an important role in mediating sorafenib resistance. The up-regulation of FASN antagonize of SLC7A11-mediated ferroptosis and thereby promoted sorafenib resistance. Mechanistically, FASN enhanced sorafenib-induced ferroptosis resistance by binding to hypoxia-inducible factor 1-alpha (HIF1α), promoting HIF1α nuclear translocation, inhibiting ubiquitination and proteasomal degradation of HIF1α, and subsequently enhancing transcription of SLC7A11. Orlistat, an inhibitor of FASN, with sorafenib had significant synergistic antitumor effects and reversed sorafenib resistance both in vitro and in vivo. Conclusion Targeting the FASN/HIF1α/SLC7A11 pathway resensitized HCC cells to sorafenib. The combination of orlistat and sorafenib had superior synergistic antitumor effects in sorafenib-resistant HCC cells.

Cancer is a broad term used to describe a large number of diseases characterized by uncontrolled cell proliferation that leads to tumor production. Cancer is associated with mutations in genes controlling proliferation and apoptosis, oxidative stress, fatty acid synthase (FAS) expression, and other mechanisms. Currently, most antineoplastic drugs have severe adverse effects and new effective and safe drugs are needed. This study aims to investigate the possible anticancer activity of rutin and orlistat which are both safely used clinically in humans against two breast cancer models (in vivo EAC and in vitro MCF7) and the pancreatic cancer cell line (PANC-1). Our results have shown that both rutin and orlistat exerted an in vivo anticancer activity as evidenced by the decrease in tumor volume, CEA level, cholesterol content, FAS, and the exerted antioxidant action (reduced MDA level and increased GSH content) and through histopathological examination. In addition, both were cytotoxic to MCF-7 and Panc-1 cell lines by promoting apoptosis. In conclusion, the anticancer activity of rutin and orlistat makes them promising candidates for cancer treatment alone or in combination with other anticancer drugs specially that they are used clinically with an acceptable safety profile.

The present study aimed to develop orlistat-loaded solid self-nanoemulsifying drug delivery system preconcentrate (SSP) with the minimum use of lipid excipients for the enhanced solubility, in vitro dissolution, lipase inhibition, and in vivo performance. In the screening of solubilizing vehicles, Solutol HS15 and Lauroglycol 90 were selected as the surfactant and oil phase, respectively. A pseudo-ternary phase diagram composed of Solutol HS15, Lauroglycol 90, and orlistat as an anti-obesity agent and lipid component was constructed, and the SSP regions were confirmed in terms of the particle size distribution in water, melting point by differential scanning calorimetry, and crystallinity by X-ray diffraction. Physicochemical interaction between Solutol HS15 and orlistat resulted in SSP with various melting points in the range of 26°~33°C. The representative maximum orlistat-loaded SSP (orlistat/Solutol HS15/Lauroglycol 90=55/40/5, weight ratio) showed the melting point of 32.23°C and constructed uniform nanoemulsion with the particle size of 141.7±1.1 nm dispersed in water. In the dissolution test at pH 1.2 without any detergent, the SSP reached 98.12%±0.83% until 45 minutes, whereas raw orlistat showed no significant dissolution rate. The dissolution samples containing SSP showed a lipase inhibition of 90.42%±1.58% within 45 minutes. In terms of the reduction level of fat absorption in rats, the intake group of SSP gave a significantly higher fat excretion into stool than the one observed in the raw orlistat group ( <0.05). In conclusion, the suggested novel SSP formulation would be an effective and promising candidate for the treatment of obesity.

Obesity represents a significant global public health issue, contributing to the rising prevalence of metabolic diseases. One treatment for obesity is orlistat, a drug that inhibits pancreatic lipase. It is widely used due to its efficacy in reducing dietary fat absorption. However, patient adherence to this drug is often hindered by its associated adverse effects. As a result, there is an increasing interest in exploring alternative therapeutic options derived from natural sources, such as plants and algae, particularly extracts and their bioactive compounds. These extracts and compounds have shown potential in inhibiting pancreatic lipase and other markers associated with obesity. Nevertheless, they also present certain limitations, including low bioavailability. In this context, combination therapy involving orlistat and these extracts or their compounds has emerged as a promising strategy. This approach aims to enhance the inhibition of pancreatic lipase and other obesity-related markers, thereby improving therapeutic outcomes and reducing adverse effects associated with treatment. The objective of this review is to analyze the available scientific evidence regarding the combined effects of orlistat and extracts or bioactive compounds in inhibiting various markers related to dyslipidemia and obesity, with the goal of proposing combination therapy as a safe and effective therapeutic option.

Thistle (Onopordum acanthium) has been traditionally employed for liver protection. However, we recently identified silibinin, the main bioactive compound of thistle extract, as an in vitro pancreatic lipase inhibitor, which suggested a potential role as an anti-obesity agent. This study aimed to assess, in vivo, the efficacy, safety, and effects of silibinin on human lipase. As a secondary objective, we evaluated potential changes in gut microbiota after silibinin treatment. A randomized trial comparing 150 mg/silibinin, 300 mg/silibinin, and a thistle extract (equivalent to 150 mg/silibinin) with placebo and orlistat/120 mg was conducted. Fecal fat excretion, clinical parameters, and microbiota changes were analyzed. Orlistat showed the highest fecal fat excretion, although thistle extract had similar results (p = 0.582). The 150 mg/silibinin group reported the fewest adverse effects. Both silibinin and orlistat reduced plasma triglycerides (p = 0.016) and waist circumference (p = 0.001). Specific microbiota changes, such as increases in Mycobacteriaceae and Veillonellaceae, were associated with higher fat excretion. Although the present work was conducted in the short term and in people of normal weight, our results suggest that silibinin may be safe and effective for obesity, with minimal adverse effects and no significant changes in microbiota diversity. Further studies are needed to explore its microbiota-related benefits.

The inhibition of recombinant CpLIP2 lipase/acyltransferase from Candida parapsiolosis was considered a key model for novel antifungal drug discovery and a potential therapeutic target for candidiasis. Lipases have identified recently as potent virulence factors in C. parapsilosis and some other yeasts. The inhibition effects of orlistat and four flavonols (galangin, kaempferol, quercetin and myricetin) characterized by an increasing degree of hydroxylation in B-ring, were investigated using ethyl oleate hydrolysis as the model reaction. Orlistat and kaempferol (14 µM) strongly inhibited CpLIP2 catalytic activity within 1 min of pre-incubation, by 90% and 80%, respectively. The relative potency of flavonols as inhibitors was: kaempferol > quercetin > myricetin > galangin. The results suggested that orlistat bound to the catalytic site while kaempferol interacted with W294 on the protein lid. A static mechanism of interactions between flavonols and CpLIP2 lipase was confirmed by fluorescence quenching analyses, indicating that the interactions were mainly driven by hydrophobic bonds and electrostatic forces. From the Lehrer equation, fractions of tryptophan accessibility to the quencher were evaluated, and a relationship with the calculated number of binding sites was suggested.

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.

Orlistat is a potent lipase inhibitor utilized as a preventive agent for obesity and fat absorption control. Existing literature presents conflicting findings regarding its impact on lipid parameters. This systematic review followed the PRISMA guidelines and was registered in PROSPERO (ID: CRD42024550889). A comprehensive search of PubMed, Scopus, Web of Science, and Cochrane Register of Controlled Trials was conducted for studies published before January 19, 2025. Eligible studies included randomized controlled trials (RCTs) evaluating orlistat in adults (≥ 18 years) with dyslipidemia. Furthermore, the Grading of Recommendations, Assessment, Development, and Evaluations assessment tool was employed to analyze the certainty of evidence or each outcome. A total number of 1369 participants, with 682 in treatment and 687 in control categories, were included in our study. Orlistat reduced body mass index (BMI) (SMD [95% CI]: -0.30 [-0.58, -0.03], value (heterogeneity) = 0.026), and also it was associated with a decrease in high-density lipoprotein cholesterol (SMD (95% CI): -0.31 [-0.48, -0.13], value (heterogeneity) = 0.436). Changes in waist circumference (WC) and triglycerides (TGs) did not reach statistical significance in the primary analysis (WC: SMD [95% CI] -0.1562 [-0.3138; 0.0015],  = 0.0%, -value (heterogeneity) = 0.7572; TG: SMD [95% CI] -0.1668 [-0.7979; 0.4642],  = 97.7% value (heterogeneity) < 0.0001); however, after publication-bias adjustment using the trim-and-fill sensitivity analysis, meaningful reductions were discovered for WC (SMD (%95CI): -0.1712 [-0.3248; -0.0176],  = 0.0%, value (heterogeneity) = 0.7696) and TG (SMD (%95CI): -0.8900 [-1.6619; -0.1181],  = 97.9%, value (heterogeneity) < 0.0001). The secondary analysis demonstrated that follow-up duration accounted for 30% of TG heterogeneity, suggesting a small but significant decline in orlistat's TG-lowering effect over time (slope: -0.1239; 95% CI: -0.2355, -0.0123; value = 0.0295). No significant changes were observed in other parameters of the study. Besides, gastrointestinal issues were the most frequently reported adverse events among the studies. Our findings suggest that orlistat meaningfully reduces BMI but is associated with decreased HDL-C, which may be undesirable given HDL-C's protective role in cardiovascular health. Evidence for reductions in TG and WC is uncertain: the primary meta-analysis showed no statistically significant effects, whereas trim-and-fill sensitivity analysis suggested potential reductions. No significant short-term impact on TG was observed, though a modest reduction may emerge with prolonged use.

Staphylococcus aureus lipase (SAL), a triacylglycerol esterase, is an important virulence factor and may be a therapeutic target for infectious diseases. Herein, we determined the 3D structure of native SAL, the mutated S116A inactive form, and the inhibitor complex using the anti-obesity drug orlistat to aid in drug development. The determined crystal structures showed a typical α/β hydrolase motif with a dimeric form. Fatty acids bound near the active site in native SAL and inactive S116A mutant structures. We found that orlistat potently inhibits SAL activity, and it covalently bound to the catalytic Ser116 residue. This is the first report detailing orlistat–lipase binding. It provides structure-based information on the production of potent anti-SAL drugs and lipase inhibitors. These results also indicated that orlistat can be repositioned to treat bacterial diseases.